Dietary Cocoa Flavanols and Age-Related Memory Decline
Phase: NA
Conditions: Memory Loss
Sponsor: New York State Psychiatric Institute

1  
Di et ar y  Fl a v a n ol s a n d  D e nt at e  G yr u s F u n cti o n 
St u d y  Pr ot o c ol
Tri al R e gi str ati o n
cli ni c altri al s. g o v I d e ntifi er: N C T 0 2 3 1 2 3 1 0; 
htt p s:// cli ni c altri al s. g o v/ ct 2/ s h o w/ N C T 0 2 3 1 2 3 1 0
St u d y Pr ot o c ol p a g e 1

Si g ne d c o p y o n file at I R B  
 
             v. 1 1/ 1 5/ 1 3  
Ne w Y or k St ate Ps yc hi atric I nstit ute  
I nstit uti o n al Re vie w B o ar d 
 
Dec e m b er 1 7 , 2 0 19  
 
 
T o : 
 
Dr. Ric har d Sl oa n  
Fr o m :  
Dr. E d war d N u nes, I R B C o -C hair  
 
 
Dr. A g nes W hita ker, I R B C o-C hair   
 
 
 
 
S u bject : 
A p pr o val N otice : C O N TI N U A TI O N E x pe dite d per 4 5 C F R 4 6. 1 1 0( b)( 1)(f)( 8c)  
 
 
  
 
 
 
 
Y o ur pr ot oc ol # 7 0 3 4  e ntitle d: D I E T A R Y C O C O A F L A V A N O L S A N D A G E -R E L A T E D M
E M O R Y 
D E C LI N E  Pr ot oc ol versi o n date 1 2 /1 7 / 2 0 19  has bee n a p pr o ve d b y t h e Ne w Y or k State Ps yc hi atric 
I nstit ute - C ol u m bia U ni versit y D e part me nt of Ps yc hi atr y I nstit uti o nal Re vie w B oar d fr o m 
Dec e m b er 1 7 , 2 0 18  t o O ct o ber  1 9 , 2 02 0 .  
 
C o nse nt re q uire me nts : 
     √  N ot a p plica ble: Dat a A nal ysis O nl y  
    4 5 C F R 4 6. 1 1 6 ( d ) wai ver of c o nse nt f or t he tel e p h o ne scree n 
      Si g nat ure b y t h e pers o n(s) o btai ni n g c o nse nt is re q uire d t o d oc u me nt t he c o nse nt pr ocess  
      D oc u me ntati o n of a n i n de pe n de nt assess me nt of t he partici pa nt’s ca p acit y t o c o nse nt is als o 
re q uire d. 
A p pr o ve d f or recr uit me nt of s u bjects w h o l ac k c a p acit y t o c o nse nt : √ N o  Yes    
 
 
Fiel d M o nit ori n g Re q uire me nts:  √ R o uti ne S pecial: _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
 
 
  O nl y c o pies of c o nse nt d oc u me nts t hat are c urre ntl y a p pr o ve d b y t he I R B ma y be us e d t o o btai n 
c o nse nt f or partici pati o n i n t his st u d y.  
  A pr o gress re p ort a n d a p plicati o n f or c o nti n ui n g re vie w is re q uire d 2 m o nt hs pri or t o t he 
e x pirati o n date of I R B a p pr o val.  
  C ha n ges t o t his researc h ma y n ot be i nitiate d wit h o ut t he re vie w a n d a p pr o val of t he I R B e x ce pt 
w he n necessar y t o eli mi nate i m me diate hazar ds t o partici pa nts.  
  All seri o us a n d/ or u na ntici pate d pr o ble ms or e v e nt s i n v ol vi n g ris ks t o s u bjects or ot hers m ust be 
re p orte d i m me diatel y t o t he I R B.  Pleas e refer t o t he PI-I R B we bsite at htt p://ir b. n ys pi. or g  f or 
A d verse E v e nt Re p orti n g Pr oce d ures a n d a d diti o nal re p orti n g re q uire me nts.    
 
Cc:  
C U  B usi ness Office ( M ars I nc ) 
 
 
E N /A H W/ al w 

Pr ot oc ol S u m m ar y F or m
7 0 3 4
Sl oa n, Ric har d
P a g e 1 of 2 6
Pr ot oc ol Title:
Diet ar y C oc o a Fl a v a n ols a n d A ge- Rel ate d 
Me m or y  Decli ne
Pr ot oc ol N u m ber:
7 0 3 4
First A p pr o val:
1 1/ 2 0/ 2 0 1 4
E x pirati o n Date:
1 0/ 1 9/ 2 0 2 0
Versi o n Date:
1 2/ 1 7/ 2 0 1 9
C o ntact Pri nci pal I n vesti gat or:
Ric h ar d Sl o a n, P H D
E m ail: r ps 7 @c ol u m bi a.e d u
Tele p h o ne: 6 4 6- 7 7 4- 8 9 4 0
C o-I n vesti gat or(s):
Sc ott S m all
A d a m Bric k m a n, P H D
C o v er S h e et
C h o ose O N E  o pti o n fr o m t he f oll o wi n g t hat is a p plica ble t o y o ur st u d y
If y o u are creati n g a ne w pr ot oc ol, select "I a m s u b mitti n g a ne w pr ot oc ol." As 5 Year Re ne wals are n o 
l o n ger re q uire d, t his o pti o n re mai ns f or hist orical p ur p oses.
I a m s u b mitti n g a n a n n ual c o nti n uati o n wit h o ut m o dificati o ns 
Di vi si o n & P er s o n n el
Di visi o n
W hat Di visi o n/ De part me nt d oes t he PI bel o n g t o?
Be ha vi oral Me dici ne/ Ps yc hiatr y
Wit hi n  t he di visi o n/ de part me nt, w hat Ce nter or gr o u p are y o u affiliate d wit h, if a n y? 
n o ne
U n affili ate d Pers o n nel
List i n vesti gat ors, if a n y, w h o will be  partici pati n g i n t his pr ot oc ol b ut are n ot affiliate d wit h Ne w Y or k 
State Ps yc hiatric I nstit ute or C ol u m bia U ni versit y. Pr o vi de: F ull Na me, De grees a n d Affiliati o n.
n o ne

Pr ot oc ol S u m m ar y F or m
7 0 3 4
Sl oa n, Ric har d
P a g e 2 of 2 6
A p pli c ati o n f or C o nti n u ati o n of R e s e ar c h
St at us
C urre nt Stat us of St u d y: 
All  researc h i nter ve nti o ns were c o m plete d. O nl y data a nal ysis is o n g oi n g.
S u m m ar y of E x perie nces t o D ate
Please  pr o vi de a s u m mar y of scie ntific pr o gress of t he st u d y a n d t he e x perie nce of researc h partici pa nts, t o 
date. T his re q uire me nt is desi g ne d t o all o w f or t he i n vesti gat or a n d t he I R B t o reassess t he st u d y’s ris ks a n d 
be nefits i n ter ms of de vel o p me nts i n t he fiel d, c ha n gi n g practice patter ns, a n d ne w I R B p olicies a n d 
pr oce d ures.
Recr uit me nt a n d pr oce d ures f or t he I R B Pr ot oc ol # 7 0 3 4 - Dietar y C oc oa Fla va n ols a n d A ge- Relate d 
Me m or y Decli ne - is c o m plete a n d o nl y data a nal ysis is o n g oi n g. We ha ve scree ne d 2 5 8 9 partici pa nts, 
e nr olle d 2 5 3, a n d ra n d o mize d 2 1 1. Of t hese, 2 0 4 ha ve c o m plete d t heir 1 2 wee k visit a n d 1 9 7 ha ve 
c o m plete d t heir 2 0 wee k visit. 5 8 partici pa nts ha ve bee n e nr olle d i n t he M RI ar m of t he st u d y.
F u n di n g
Ha ve t here bee n a n y c ha n ges i n f u n di n g stat us si nce t he pri or a p pr o val? 
N o
Ha ve t he  pri nci pal i n vesti gat or a n d ot her i n vesti gat ors ma de all re q uire d discl os ures of fi na ncial i nterest i n 
t he st u d y s p o ns or/ pr o d uct?
Yes
S u m m ar y
Ha ve t here bee n a n y st u d y fi n di n gs, rece nt literat ure, or u nt o war d e ve nts occ uri n g here or at ot her sites i n 
t he past year w hic h mi g ht affect t he a nal ysis of t he safet y, ris ks or be nefits of st u d y partici pati o n? 
N o
Ha ve t here bee n a n y seri o us a d verse e ve nts (seri o us a n d/ or u na ntici pate d pr o ble ms i n v ol vi n g ris ks t o 
s u bjects or ot hers at t his site w hic h occ ure d i n t he past year)? 
N o
Ha ve all st u d y staff wit h a si g nifica nt r ole i n t he desi g n or i m ple me ntati o n of t he h u ma n s u bject c o m p o ne nts 
of t his st u d y recei ve d re q uire d trai ni n g i n h u ma n researc h s u bject pr otecti o ns?
Yes
Is t he st u d y c o vere d b y a certificate of c o nfi de ntialit y? 
N o
O ver all Pr o gress
A p pr o ve d sa m ple size
2 6 0
T otal n u m ber of partici pa nts  e nr olle d t o date

Pr ot oc ol S u m m ar y F or m
7 0 3 4
Sl oa n, Ric har d
P a g e 3 of 2 6
2 5 3
N u m ber of partici pa nts w h o ha ve  c o m plete d t he st u d y t o date 
2 1 1
Ha ve t here bee n a n y si g nifica nt de viati o ns fr o m t he a ntici pate d st u d y recr uit me nt, rete nti o n or c o m pleti o n 
esti mates? 
N o
C o m me nts / a d diti o nal i nf or mati o n 
N/ A
S a m ple De m o gr a p hics
S pecif y p o p ulati o n
Healt h y A d ults
T otal n u m ber  of partici pa nts e nr olle d fr o m t his p o p ulati o n t o date 
2 5 3
Ge n der, Racial a n d Et h nic Brea k d o w n 

Pr ot oc ol S u m m ar y F or m
7 0 3 4
Sl oa n, Ric har d
P a g e 4 of 2 6
S u m m ar y of C urre nt Ye ar's  E nr oll me nt a n d Dr o p- o ut 
N u m ber of partici pa nts w h o si g ne d c o nse nt  i n t he past year
0
Di d t he i n vesti gat or wit h dra w partici pa nts fr o m t he st u d y? 

Pr ot oc ol S u m m ar y F or m
7 0 3 4
Sl oa n, Ric har d
P a g e 5 of 2 6
Yes
Circ u msta nces of wit h dra wal:
Partici pa nts  faile d t o s uccessf ull y c o m plete t he r u n-i n p orti o n of t he st u d y.
Di d partici pa nts deci de t o disc o nti n ue st u d y i n v ol ve me nt? 
N o
Pr o c e d ur e s
T o cre ate t he pr ot oc ol s u m m ar y f or m, first i n dic ate  if t his rese arc h will i ncl u de a n y of t he f oll o wi n g 
pr oce d ures
   N e ur o p s y c h ol o gi c al E v al u ati o n
   C oll e cti o n of Bi ol o gi c al S p e ci m e n s
   M RI
   I nt er n et- b a s e d D at a C oll e cti o n or Tr a n s mi s si o n
P o p ul ati o n
I n dic ate w hic h of t he f oll o wi n g p o p ul ati o ns will be i ncl u de d i n t his rese arc h
   M e di c all y a n d P s y c hi atri c all y H e alt h y S u bj e ct s
   A d ult s
   A d ult s o v er 5 0
R e s e ar c h S u p p ort/ F u n di n g
Will a n e xisti n g i nter nal acc o u nt be use d t o s u p p ort t he pr oject?
N o
Is t he pr oject e xter nall y f u n de d or is e xter nal f u n di n g pla n ne d?
Yes
Select t he n u m ber of e xter nal s o urces of f u n di n g t hat will be a p plica ble t o t his st u d y
F u n di n g S o urce # 1
Is t he PI of t he gra nt/c o ntract t he sa me as t he PI of t he I R B pr ot oc ol? 
Yes
Select o ne  of t he f oll o wi n g
T he gra nt/c o ntract is c urre ntl y f u n de d
S o urce of F u n di n g
F o u n dati o n
S p o ns or
Mars I nc or p orate d 

Pr ot oc ol S u m m ar y F or m
7 0 3 4
Sl oa n, Ric har d
P a g e 6 of 2 6
Select o ne of t he f oll o wi n g
Si n gle Site
B usi ness Office
C U
D oes  t he gra nt/c o ntract i n v ol ve a s u bc o ntract? 
N o
St u d y L o c ati o n
I n dicate if t he researc h is/ will be c o n d ucte d at a n y of t he f oll o wi n g
   Ot h er C ol u m bi a U ni v er sit y M e di c al C e nt er F a ciliti e s
T his pr ot oc ol  descri bes researc h c o n d ucte d b y t he PI at ot her facilities/l ocati o ns
N o
L a y S u m m ar y of Pr o p o s e d R e s e ar c h 
La y S u m mar y of Pr o p ose d Researc h
I n o ur pre vi o us st u d y, we f o u n d t hat c o ns u mi n g a diet ric h i n c oc oa fla va n ols ( 9 0 0 m g per da y, acc or di n g t o 
t he ol der assa y use d t o q ua ntif y c oc oa fla va n ols) f or t hree m o nt hs i m pr o ve d i ma gi n g a n d c o g niti ve 
meas ures of me m or y. We are c o n d ucti n g t his researc h t o c o nfir m a n d e xte n d t he fi n di n g t hat a dietar y 
fla va n ol i nta ke i m pr o ves a ge-relate d me m or y decli ne. 
 
I n t his st u d y, we will recr uit 2 6 0 s u bjects, 2 0 0 of w h o m will meet i ncl usi o n a n d e xcl usi o n criteria. S u bjects 
will be scree ne d b y p h o ne a n d t he n i n pers o n t o e ns ure t he y meet i ncl usi o n criteria. T he y will c o m plete a 
me dical hist or y q uesti o n naire. We will als o c o n d uct a n o pti o nal M RI s u b-st u d y. S u bjects w h o e x press 
i nterest will c o m plete a cla ustr o p h o bia q uesti o n naire, a n d will be scree ne d f or c o n diti o ns t hat c o ntra-
i n dicate M RI st u dies. T he M o ntreal C o g niti ve Assess me nt ( M o C A) will als o be a d mi nistere d bef ore fi nal 
eli gi bilit y is deter mi ne d. S u bjects will be ra n d o mize d t o o ne of f o ur gr o u ps, t he me m bers of w hic h will be 
assi g ne d a s pecific dail y c oc oa fla va n ol i nta ke a m o u nt ( 0 m g, 2 2 5 m g, 4 0 0 m g or 6 5 0 m g per da y +/ = 1 0 % * 
per da y), res pecti vel y. S u bjects will ta ke t he c oc oa fla va n ols f or 1 2 wee ks d uri n g w hic h t he y will c o m plete 
ne ur o ps yc h ol o gical testi n g at wee k 4 of t he 1 2- wee k peri o d. After t he 1 2 wee ks, s u bjects will ret ur n f or 
f oll o w- u p assess me nt of ne ur o ps yc h ol o gical testi n g a n d M RI, if t he y partici pate i n t he o pti o nal M RI s u b-
st u d y. Ei g ht wee ks after t he last c oc oa fla va n ol i nta ke, s u bjects will c o m plete a fi nal ne ur o ps yc h ol o gical 
testi n g. 
 
* As a f o o d pr o d uct wit h nat ural  variati o n, c oc oa e xtract C F val ues de n ote d t hr o u g h o ut t his pr ot oc ol are 
s u bject t o a varia nce of +/- 1 0 %. T hese val ues, base d o n a ne w a n d differe nt assa y f or c oc oa fla va n ols, 
c orres p o n d t o 3 0 0 m g, 6 0 0 m g, a n d 9 0 0 m g of c oc oa fla va n ols deri ve d fr o m a n ol der assa y n o l o n ger use d 
b y Mars S y m bi oscie nce. 

Pr ot oc ol S u m m ar y F or m
7 0 3 4
Sl oa n, Ric har d
P a g e 7 of 2 6
B a c k gr o u n d, Si g nifi c a n c e a n d R ati o n al e
Bac k gr o u n d,  Si g nifica nce a n d Rati o nale
   T he prefr o ntal c orte x[ 1] a n d t he hi p p oca m pal f or mati o n[ 2] are t w o brai n areas t hat are affecte d b y a gi n g 
a n d are t h o u g ht t o c o ntri b ute t o a ge-relate d me m or y decli ne[ 3]. T he hi p p oca m pal f or mati o n itself is a circ uit 
ma de u p of i nterc o n necte d re gi o ns[ 4]. Eac h re gi o n h o uses a p o p ulati o n of m olec ularl y a n d f u ncti o nall y 
disti nct ne ur o ns, w hic h acc o u nts f or w h y i n di vi d ual re gi o ns are differe ntiall y affecte d b y a gi n g a n d 
disease[ 4]. I n h u ma ns[ 5, 6], n o n- h u ma n pri mates[ 7, 8], a n d r o de nts[ 7, 9, 1 0] t he de ntate g yr us ( D G) is t he 
re gi o n of t he hi p p oca m pal circ uit t hat has s h o w n t he m ost c o nsiste nt a ge-relate d c ha n ges usi n g vari o us 
i n dicat ors of f u ncti o nal i nte grit y. Ne vert heless, beca use t hese o bser vati o ns are o nl y c orrelati o nal, a q uesti o n 
re mai ns as t o w het her D G d ysf u ncti o n directl y c o ntri b utes t o a ge-relate d me m or y decli ne a n d w het her a n 
i nter ve nti o n t hat i m pr o ves D G f u ncti o n will a meli orate me m or y decli ne i n ol der s u bjects. 
   A rece nt st u d y i n y o u n g mice s h o we d t hat oral c o ns u m pti o n of e picatec hi n, a dietar y fla va n ol, i m pr o ve d 
D G a n d me m or y f u ncti o n a n d t hat t his i m pr o ve me nt was e n ha nce d b y aer o bic e xercise[ 1 1]. We 
h y p ot hesize d t hat a dietar y s u p ple me nt hi g h i n e picatec hi n, per ha ps t o get her wit h e xercise, w o ul d e n ha nce 
D G f u ncti o n i n ol der h u ma ns, a n d t hat t his e n ha nce me nt w o ul d me diate a n i m pr o ve me nt i n c o g niti ve 
perf or ma nce. 
   Usi n g a varia nt of f M RI t hat relies o n stea d y-state c o ntrast e n ha nce me nt t o ge nerate basal ma ps of 
cere bral bl o o d v ol u me ( C B V)[ 1 2], we i de ntifie d a ge-relate d decli ne D G d ysf u ncti o n a n d disti n g uis he d it 
fr o m re gi o ns of t he hi p p oca m pal circ uit t hat are ass ociate d wit h Alz hei mer’s disease ( A D)[ 7, 9, 1 3]. 
   Ne xt, i n a ntici pati o n of a n i nter ve nti o n st u d y, we de vel o pe d a c o g niti ve tas k t hat l ocalizes, at least i n part, 
t o t he site of a ge-relate d C B V decli ne. T his tas k, t he m o difie d Be nt o n Vis ual Rete nti o n Test ( M o d Be nt), 
selecti vel y c orrelate d wit h D G C B V. M ore o ver, M o d Be nt perf or ma nce w orse ns wit h a ge, at a rate of 
a p pr o xi matel y 2 2 0 ms per deca de ( β = 2 2. 3 1, p < 0. 0 0 1). 
   We t he n desi g ne d a d o u ble- bli n d 3- m o nt h i nter ve nti o n st u d y i n w hic h healt h y b ut se de ntar y s u bjects, 
bet wee n a ges of 5 0- 7 0, were ra n d o ml y assi g ne d t o o ne f o ur e x peri me ntal gr o u ps: S u bjects eit her recei ve d a 
dail y dietar y s u p ple me nt of hi g h fla va n ols ( 9 0 0 m g per da y, acc or di n g t o t he ol der assa y use d t o q ua ntif y 
c oc oa fla va n ols) e nric he d i n e picatec hi n[ 1 4], wit h or wit h o ut a re gi me n of aer o bic fit ness; or a dietar y 
s u p ple me nt of l o w fla va n ols ( 4 5 m g per da y), wit h or wit h o ut a re gi me n of aer o bic fit ness trai ni n g. T he 
aer o bic fit ness re gi me n c o nsiste d of 1 h o ur per da y of aer o bic e xercise, f o ur da ys per wee k. All s u bjects 
were i ma ge d wit h C B V-f M RI a n d were e val uate d wit h t he M o d Be nt at baseli ne, a n d t he n a sec o n d ti me at 
t he e n d of t he st u d y. Besi des C B V-f M RI a n d M o d Be nt as t he pri mar y o utc o me meas ures, aer o bic ca pacit y 
( V O 2 ma x) was i ncl u de d as a sec o n dar y meas ure t o deter mi ne w het her t he aer o bic fit ness re gi me n was 
effecti ve. 
   Res ults re veale d t hat t he dietar y i nter ve nti o n ha d a si g nifica nt effect o n M o d Be nt perf or ma nce, 
i n de pe n de nt of e xercise (t = 2. 1 7, p = . 0 3 8). U ne x pecte dl y, e xercise ha d n o effect o n V O 2 ma x a n d s o t he 
e xercise i nter ve nti o n was c o nsi dere d a treat me nt fail ure. 
   O ur ai m i n t his c urre nt pr o p osal is t o re plicate t his fi n di n g a n d t o f urt her e x pl ore t he effects of differe nt 
dail y i nta ke a m o u nts of t he fla va n ol dietar y s u p ple me nt a n d t he ti me c o urse of t hese effects.  
S p e cifi c Ai m s a n d H y p ot h e s e s

Pr ot oc ol S u m m ar y F or m
7 0 3 4
Sl oa n, Ric har d
P a g e 8 of 2 6
S pecific Ai ms a n d H y p ot heses
S pecific Ai m:   T o c o nfir m a n d e xte n d t he fi n di n g t hat a dietar y c oc oa fla va n ol i nta ke i m pr o ves a ge-relate d 
me m or y decli ne.
I n o ur pre vi o us st u d y, we f o u n d t hat c o ns u mi n g a diet ric h i n c oc oa fla va n ols ( 9 0 0 m g per da y, acc or di n g t o 
t he ol der assa y use d t o q ua ntif y c oc oa fla va n ols) f or t hree m o nt hs i m pr o ve d i ma gi n g a n d c o g niti ve 
meas ures of me m or y decli ne.
T w o q uesti o ns re mai n u n k n o w n:
A) t he ti me c o urse  of t he effect.
B) W het her differe nt dail y i nta ke le vels of t he fla va n ols  will pr o d uce differe nt effects o n c o g niti ve a n d 
i ma gi n g o utc o mes.
 
We pla n o n st u d yi n g b ot h q uesti o ns b y testi n g f o ur differe nt dail y i nta ke a m o u nts of c oc oa fla va n ols: 0 m g, 
2 2 5 m g, 4 0 0 m g  a n d 6 5 0 m g. 
D e s cri pti o n of S u bj e ct P o p ul ati o n
S a m ple # 1
S pecif y s u bject p o p ulati o n
Healt h y a d ults
N u m ber  of c o m pleters re q uire d t o acc o m plis h st u d y ai ms
2 0 0
Pr ojecte d n u m ber of s u bjects w h o will be e nr olle d t o o btai n re q uire d n u m ber of c o m pleters
2 6 0
A ge ra n ge of s u bject p o p ulati o n
5 0- 7 5
Ge n der, Racial a n d Et h nic Brea k d o w n
As wit h  past st u dies carrie d o ut i n t he C ol u m bia U ni versit y Me dical Ce nter ca m p us ( 1 7. 4 % Africa n 
A merica n, 1 0. 5 % His pa nic, 1 6. 4 % Asia n, 4 8 % W hite a n d 7. 7 % U n k n o w n) t he p o p ulati o n of Ne w Y or k 
Cit y is c orres p o n di n gl y et h nicall y di verse. 
 
 
Africa n 
A merica n
His pa nic
Asia n or Pacific 
Isla n der
W hite
Ot her or 
u n k n o w n
T otal
Fe male 
 
2 1
1 3
2 0
5 7
9
1 2 0
Male 
 
1 4
8
1 3
3 9
6
8 0
T otal
3 5
2 1
3 3
9 6
1 5
2 0 0

Pr ot oc ol S u m m ar y F or m
7 0 3 4
Sl oa n, Ric har d
P a g e 9 of 2 6
 
Descri pti o n of s u bject p o p ulati o n
2 6 0 s u bjects  will  be recr uite d, a ges 5 0- 7 5. S u bjects will be recr uite d fr o m t he c o m m u nit y wit hi n Ne w Y or k 
Cit y t hr o u g h ma n y m o dalities, i ncl u di n g fl yers, a n n o u nce me nts, a n d p osti n gs o n we bsites a n d i n 
ne wsletters. T hese a p pr oac hes t o recr uit me nt ha ve bee n hi g hl y s uccessf ul i n t he past. As wit h past st u dies 
carrie d o ut i n t he C ol u m bia U ni versit y Me dical Ce nter ca m p us ( 1 7. 4 % Africa n A merica n, 1 0. 5 % His pa nic, 
1 6. 4 % Asia n, 4 8 % W hite a n d 7. 7 % U n k n o w n) t he p o p ulati o n of Ne w Y or k Cit y is c orres p o n di n gl y 
et h nicall y di verse. Si xt y perce nt of t he s u bjects i n eac h gr o u p will be fe male. 
R e cr uit m e nt Pr o c e d ur e s
Descri be setti n gs w here recr uit me nt will occ ur
   S u bjects will be recr uite d b y p osti n g a n d passi n g o ut fl yers a n d br oc h ures at C ol u m bia U ni versit y ca m p us 
a n d t he l ocal c o m m u nit y. We als o will p urc hase pri nt a ds i n l ocal ne ws pa pers. We als o pla n t o p u blis h t he 
a ds i n Crai g’s List a n d o n Face b o o k. T hese i nter net a ds will be i de ntical t o t he pri nt a ds. I n a d diti o n, we will 
use ra di o br oa dcast i n t he f or m of p u blic ser vice a n n o u nce me nts a n d pai d a d vertise me nts o n l ocal ra di o 
stati o ns.   M ore o ver, s u bjects will be recr uite d b y ta bli n g at healt h-relate d a n d c o m m u nit y e ve nts. We will 
als o p ost o ur st u d y o n Researc h Matc h a n d  Recr uit Me, C ol u m bia U ni versit y Me dical Ce nter’s recr uit me nt 
re gistr y. We will als o utilize a mar ket maili n g a p pr oac h. Letters will be se nt t o a p pr o priatel y a ge d p ote ntial 
s u bjects ra n d o ml y selecte d fr o m c o m mercial lists.
H o w a n d b y w h o m will s u bjects be a p pr oac he d a n d/ or recr uite d? 
   Na mes a n d titles of pers o ns desi g nate d t o o btai n c o nse nt a n d/ or recr uit are f o u n d o n " Pers o ns desi g nate d 
t o disc uss a n d d oc u me nt c o nse nt" secti o n of t he P S F. S u bjects will be a p pr oac he d a n d/ or recr uite d b y o ur 
I R B a p pr o ve d recr uit me nt material a n d e ve nts.
H o w will t he st u d y be a d vertise d/ p u blicize d? 
   S u bjects will be recr uite d b y p osti n g a n d passi n g o ut fl yers a n d br oc h ures at C ol u m bia U ni versit y ca m p us 
a n d t he l ocal c o m m u nit y. We als o will p urc hase pri nt a ds i n l ocal ne ws pa pers. We als o pla n t o p u blis h t he 
a ds i n Crai g’s List a n d o n Face b o o k a n d T witter a n d o ur st u d y we b pa ge. T hese i nter net a ds will be i de ntical 
t o t he pri nt a ds. A u di o vis ual a d vertise me nts will be p oste d t o o ur Face b o o k a n d T witter a n d o ur st u d y 
we b pa ge as well.  We will als o use ra di o br oa dcast i n t he f or m of p u blic ser vice a n n o u nce me nts a n d pai d 
a d vertise me nts o n l ocal ra di o stati o ns. We will als o utilize a mar ket maili n g a p pr oac h. Letters will be se nt t o 
a p pr o priatel y a ge d p ote ntial s u bjects ra n d o ml y selecte d fr o m c o m mercial lists. I n a d diti o n, we will use 
Researc h Matc h a n d C U M C's Recr uit Me, t h ose w h o e x presse d i nterest will be c o ntacte d b y o ur researc h 
staff. S u bjects will a d diti o nall y be recr uite d b y ta bli n g at healt h-relate d a n d c o m m u nit y e ve nts. Researc h 
staff will o versee t he pr o m oti o nal ta bles a n d pr o vi de i ntereste d s u bjects wit h a s h ort i ntr o d ucti o n t o t he 
st u d y. S u bjects will be scree ne d b y a st u d y c o or di nat or d uri n g a tele p h o ne call. T h ose w h o meet e nr oll me nt 
criteria will be sc he d ule d f or a n a p p oi nt me nt d uri n g w hic h t he st u d y will be descri be d i n detail a n d 
i nf or me d c o nse nt will be o btai ne d. S u bjects w h o fail t o meet t he st u d y’s i ncl usi o n a n d e xcl usi o n criteria 
will n ot be per mitte d t o c o nti n ue i n t he st u d y.
 
D o y o u ha ve a ds/recr uit me nt material re q uiri n g re vie w at  t his ti me? 

Pr ot oc ol S u m m ar y F or m
7 0 3 4
Sl oa n, Ric har d
P a g e 1 0 of 2 6
N o
D oes t his st u d y  i n v ol ve a cli nical trial?
Yes
Please pr o vi de t he N C T Re gistrati o n N u m ber
N C T 0 2 3 1 2 3 1 0 
C o n c urr e nt R e s e ar c h St u di e s
Will  s u bjects i n t his st u d y partici pate i n or be recr uite d fr o m ot her st u dies? 
Yes
Descri be c o nc urre nt researc h i n v ol ve me nt
S u bjects pre vi o usl y scree ne d f or ot her st u dies c o n d ucte d b y t he Be ha vi oral Me dici ne pr o gra m at C ol u m bia 
U ni versit y Me dical Ce nter w h o were mar ke d as i neli gi ble will be c o ntacte d b y p h o ne a n d as ke d if t he y are 
i ntereste d i n t his partic ular st u d y. O nl y t h ose s u bjects w h o c o nse nte d t o bei n g re-c o ntacte d if t he y bec o me 
eli gi ble f or a n ot her st u d y i n t he f ut ure will be as ke d t o partici pate.
I n cl u si o n/ E x cl u si o n Crit eri a
Na me t he s u bject gr o u p/s u b sa m ple
All S u bjects
Create or i nsert  ta ble t o descri be t he i ncl usi o n criteria a n d met h o ds t o ascertai n t he m
I N C L U SI O N C RI T E RI A
M E T H O D O F 
A S C E R T AI N M E N T
1. Si g ne d a n d date d i nf or me d c o nse nt o btai ne d bef ore a n y trial-relate d 
acti vities. ( Trial-relate d acti vities are a n y pr oce d ure t hat w o ul d n ot ha ve 
bee n perf or me d d uri n g n or mal ma na ge me nt of t he s u bject).
Tele p h o ne Scree n 
2. Healt h y Male or Fe male s u bjects. ( Fe males  m ust be p ost- me n o pa usal)
Tele p h o ne Scree n
3. A ge bet wee n 5 0 a n d 7 5 years, b ot h i ncl usi ve.
Tele p h o ne Scree n
4. B o d y mass i n de x bet wee n 1 8. 0 a n d 3 5 k g/ m², b ot h i ncl usi ve.
Tele p h o ne Scree n
Create or i nsert ta ble t o descri be t he e xcl usi o n criteria a n d met h o ds t o ascertai n t he m
E X C L U SI O N C RI T E RI A
M E T H O D O F 
A S C E R T AI N M E N T
G E N E R A L
1. C urre ntl y u n der g oi n g me dical treat me nt,  i ncl u di n g prescri pti o n 
dr u gs/ me dicati o n.
Me dical Hist or y I nter vie w
2. Cli nicall y si g nifica nt a b n or mal he mat ol o g y,  bi oc he mistr y, uri nal ysis, 
or c oa g ulati o n scree ni n g tests, as j u d ge d b y t he I n vesti gat or. 
Me dical Hist or y I nter vie w
3. Hist or y or prese nce of ca ncer (e xce pt  basal cell s ki n ca ncer or 
Me dical Hist or y I nter vie w

Pr ot oc ol S u m m ar y F or m
7 0 3 4
Sl oa n, Ric har d
P a g e 1 1 of 2 6
s q ua m o us cell s ki n ca ncer), or a n y cli nicall y si g nifica nt car di o vasc ular, 
res pirat or y, meta b olic, re nal, he patic, gastr oi ntesti nal, e n d ocri n ol o gical 
( wit h t he e xce pti o n e ut h yr oi d str u ma), hae mat ol o gical, der mat ol o gical, 
ve nereal, ne ur ol o gical, ps yc hiatric diseases or ot her maj or dis or ders as 
j u d ge d b y t he I n vesti gat or.
4. Seate d bl o o d press ure at scree ni n g (after resti n g  f or 5 mi n i n seate d 
p ositi o n) o utsi de t he ra n ge of 9 0- 1 4 0 m m H g f or s yst olic or 5 0- 9 0 
m m H g f or diast olic (e xcl u di n g w hite-c oat h y perte nsi o n; t heref ore, if a 
re peate d meas ure me nt s h o ws val ues wit hi n t he ra n ge, t he s u bject ca n be 
i ncl u de d i n t he trial) a n d/ or resti n g s u pi ne heart rate o utsi de t he ra n ge 
5 0- 9 0 beats per mi n ute.
Meas ure me nt ta ke n at 
c o nse nt bef ore eli gi bilit y  is 
deter mi ne d
5. C urre nt De pressi o n or A n xiet y S y m pt o ms usi n g P H Q- 8 a n d 
G A D- 7. P H Q- 8 sc ore  > = 1 0 a n d/ or G A D- 7 sc ore > = 1 0 are e xcl u de d. 
( Past hist or y of dis or ders n ot e xcl usi o nar y)
I nter vie w
6. C urre ntl y ta ki n g S S RI me dicati o ns f or a n y reas o n
I nter vie w
7. Heart Diseases.
Me dical Hist or y I nter vie w
8. He patitis B or C p ositi ve stat us.
Me dical Hist or y I nter vie w
9. HI V p ositi ve stat us.
Me dical Hist or y I nter vie w
1 0. Hist or y of m ulti ple a n d/ or se vere  aller gies t o dr u gs or f o o ds or a 
hist or y of se vere a na p h ylactic reacti o n.
Me dical Hist or y I nter vie w
1 1. Use of n o n- prescri pti o n me dicati o n, her bal pr o d ucts or n utriti o nal 
s u p ple me nts d uri n g t he st u d y, a n d wit hi n t he last 4 wee ks bef ore t he 
start of t he st u d y (scree ni n g), as j u d ge d b y t he I n vesti gat or; occasi o nal 
use of as piri n, i b u pr ofe n, aceta mi n o p he n is per mitte d.
I nter vie w
1 2. A d here nce t o a  ve ga n or ve getaria n diet or t o s pecialt y/ u nc o m m o n 
diets.
I nter vie w
1 3. F o o d Aller gies t o tree n uts, s o y, c oc oa  a n d c oc oa-c o ntai ni n g 
pr o d ucts.
I nter vie w
1 4. Pe o ple w h o c h o ose t o a v oi d  caffei ne i nta ke.
I nter vie w
1 5. C urre nt or hist or y of alc o h olis m or dr u g/c he mical a b use as per 
I n vesti gat or’s j u d g me nt.
Me dical Hist or y I nter vie w
1 6. H or m o ne  Re place me nt T hera p y; C urre ntl y pre g na nt; Pre g na nt or 
lactati n g wit hi n past 6 m o nt hs; H or m o nal birt h c o ntr ol ( pill).
I nter vie w
1 7. S m o ki n g.
I nter vie w
1 8. U n willi n g t o ha ve bl o o d dra w n or a n xiet y/ na usea d uri n g  a bl o o d 
dra w. 
I nter vie w
1 9. U nc o mf orta ble c o m pleti n g me m or y a n d atte nti o n tas ks  i n t he 
E n glis h la n g ua ge
I nter vie w
2 0. M o ntreal C o g niti ve Assess me nt ( M o C A) sc ore  less t ha n 2 6.
M o ntreal C o g niti ve 
Assess me nt
2 1. I na bilit y t o s wall o w st u d y ca ps ules
I nter vie w (at C o nse nt) 
2 2. Di d n ot c o m plete t he t w o  wee ks R u n-I n Peri o d ( Partici pa nts w h o 
R u n-I n Peri o d

Pr ot oc ol S u m m ar y F or m
7 0 3 4
Sl oa n, Ric har d
P a g e 1 2 of 2 6
misse d m ore t ha n 2 i nta ke  occasi o ns o ut of 1 4 da ys ( 2 8 occasi o ns t otal) 
or if t here are > 8 ca ps ules left i n t he b ottle after t he t w o wee ks will be 
e xcl u de d). 
 
 
M RI R E L A T E D 
 
1. Car diac Pace ma ker
I nter vie w
2. I nter nal P u m p
I nter vie w
3. I ns uli n P u m p
I nter vie w
4. Tatt o o e yeli ner
I nter vie w
5. Wire s ut ures
I nter vie w
6. I nter nal Metal O bjects
I nter vie w
7. Metal Sli vers i n E ye
I nter vie w
8. Pr ost hesis
I nter vie w
9. Heari n g Ai d I m pla nts
I nter vie w
1 0. Ne ur osti m ulat or
I nter vie w
1 1. Metal Fra g me nts
I nter vie w
1 2. Brai n A ne ur ys m Cli ps
I nter vie w
1 3. Vasc ular Cli ps
I nter vie w
1 4. Breast E x pa n der
I nter vie w
1 5. Ve na Ca va Filter
I nter vie w
1 6. Heart Val ve
I nter vie w
1 7. Metal Ste nts
I nter vie w
1 8. Ast h matic s y m pt o ms wit hi n  t he past 3 years
I nter vie w
1 9. Sic kle Cell Disease
I nter vie w
2 0. Ki d ne y Disease
I nter vie w
2 1. Pre g na nt
I nter vie w
2 2. Cla ustr o p h o bic
I nter vie w
2 3. W heelc hair b o u n d
I nter vie w
2 4. Mac hi nist or e ver w or ke d  wit h hea v y metals
I nter vie w
2 5. C o ntrai n dicati o n t o Ga d oli ni u m, i ncl u di n g pri or a d verse reacti o n t o 
ga d oli ni u m, past or c urre nt  hist or y of se vere breat hi n g diffic ult y t hat 
has bee n treate d b y a p h ysicia n (e. g. ast h ma, C O P D, etc) a n d sic kle cell 
disease. Hist or y of re nal i m pair me nt or esti mate d gl o mer ular filtrati o n 
rate < 3 0 L/ mi n. 1. 7 3 2 m 2 is als o e xcl usi o nar y
I nter vie w; 
Gl o mer ular filtrati o n rate  
assesse d wit h creati ni ne 
via Stat Se ns or m o nit or
2 6. Ha d m ore t ha n o ne pre vi o us M RI sca ns wit h Ga d oli ni u m
I nter vie w
W ai v er of C o n s e nt/ A ut h ori z ati o n
I n dicate if y o u are re q uesti n g a n y of t he f oll o wi n g c o nse nt wai vers
Wai ver of c o nse nt f or  use of rec or ds t hat i ncl u de pr otecte d healt h i nf or mati o n (a HI P A A wai ver of 
A ut h orizati o n) 

Pr ot oc ol S u m m ar y F or m
7 0 3 4
Sl oa n, Ric har d
P a g e 1 3 of 2 6
N o
Wai ver or alterati o n of c o nse nt
Yes
Wai ver  of d oc u me ntati o n of c o nse nt 
N o
Wai ver of pare ntal c o nse nt 
N o
C o n s e nt Pr o c e d ur e s
Is eli gi bilit y scree ni n g f or t his st u d y c o n d ucte d u n der a differe nt I R B pr ot oc ol?
N o
Descri be pr oce d ures use d t o o btai n c o nse nt d uri n g t he scree ni n g pr ocess 
S u bjects will be scree ne d b y a st u d y c o or di nat or d uri n g a tele p h o ne call. T h ose w h o meet
e nr oll me nt criteria will be sc he d ule d f or a n a p p oi nt me nt d uri n g w hic h t he st u d y will be descri be d i n
detail a n d i nf or me d c o nse nt will be o btai ne d. At t his a p p oi nt me nt, a me dical hist or y will be ta ke n
a n d s u bjects w h o fail t o meet t he st u d y’s i ncl usi o n a n d e xcl usi o n criteria will n ot be per mitte d t o
c o nti n ue i n t he st u d y.
Descri be St u d y C o nse nt Pr oce d ures
I nf or me d c o nse nt will be d oc u me nte d wit h a si g ne d c o nse nt state me nt gi vi n g a descri pti o n of t he st u d y i n 
detail. I n t he C o nse nt F or m a n d t hr o u g h disc ussi o n wit h a researc h assista nt, s u bjects will be a d vise d f ull y 
of t he st u d y pr oce d ures, ti me re q uire d, t he p ossi ble ris ks a n d be nefits of partici pati o n, t heir ri g ht t o ref use 
partici pati o n i n t he st u d y wit h o ut prej u dice, t heir ri g ht t o ter mi nate partici pati o n at a n y m o me nt wit h o ut 
prej u dice, a n d t he na me a n d tele p h o ne n u m ber of t he I n vesti gat ors. D uri n g c o nse nt, if t he s u bject as ks or if 
a Researc h Assista nt feels t here is a n iss ue t he I n vesti gat ors s h o ul d clarif y wit h t he partici pa nt, t he Researc h 
Assista nt will i m me diatel y c o ntact Dr. Ric har d Sl oa n, or o ne of t he C o-I n vesti gat ors. At t he c o nse nt, 
s u bjects' hei g ht, wei g ht, bl o o d press ure a n d b o d y c o m p ositi o n will be meas ure d t o deter mi ne B MI. T o 
assess t he B MI a n d b o d y c o m p ositi o n of all s u bjects, we will perf or m bi oelectrical i m pe da nce a nal ysis 
( BI A). BI A will be c o n d ucte d wit h a b o d y fat a nal yzer ( B o d ystat 1 5 0 0, Vac u me d, Ve nt ura Calif or nia) b y 
a p pl yi n g a c o nsta nt l o w le vel alter nati n g electrical c urre nt t o t he i n di vi d ual via electr o des o n a scale t hat 
s u bjects ste p o n.
A d diti o nal C o nse nt Pr oce d ures f or M RI ( T he M RI is a n  o pti o nal s u b-st u d y, o nl y t h ose t hat a gree t o ha ve 
t he M RI will g o t hr o u g h t he f oll o wi n g pr oce d ures)
   Eli gi ble s u bjects will t he n c o me i n f or a c o nse nt sessi o n wit h a researc h assista nt. T he s u bject will rea d 
t hr o u g h t he C o nse nt F or m w hic h c o ntai ns s pecific i nf or mati o n a b o ut ris k fact ors f or reacti o ns t o ga d oli ni u m 
a n d re p orte d a d verse reacti o ns. S u bjects ma y c o ntact o ur st u d y p h ysicia n wit h a n y q uesti o ns or c o ncer ns 
t he y ma y ha ve re gar di n g ga d oli ni u m. T he s u bject will c o m plete a Pre- Ga d oli ni u m Assess me nt of Ris k 
f or m, w hic h will be re vie we d a n d si g ne d b y o ur st u d y p h ysicia n, Dr. Sc ott S mall. T he Pre- Ga d oli ni u m 
Assess me nt of Ris k f or m gat hers perti ne nt me dical i nf or mati o n i ncl u di n g a hist or y of ki d ne y or li ver 
disease, h y perse nsiti ve reacti o ns t o c o ntrast a ge nts or relate d aller ge ns. S u bjects w h o ha ve a n y M RI or 
ga d oli ni u m-relate d c o ntrai n dicati o ns will n ot be c o nsi dere d eli gi ble. Eli gi ble s u bjects will meet wit h a 
re gistere d n urse, a n M D fell o w, t he atte n di n g p h ysicia n, or t he Direct or of t he M RI, w h o will prese nt t he 

Pr ot oc ol S u m m ar y F or m
7 0 3 4
Sl oa n, Ric har d
P a g e 1 4 of 2 6
se parate c o nse nt f or m f or t he M RI a n d ga d oli ni u m a n d o btai n t he s u bject’s si g nat ure i n pers o n.  S u bjects  
will als o c o m plete a Ga d oli ni u m Q uiz bef ore t he M RI sca n. 
I n dicate w hic h of t he f oll o wi n g are e m pl o ye d as a part of scree ni n g or mai n st u d y c o nse nt pr oce d ures
   C o n s e nt F or m
J u stifi c ati o n f or W ai v er or Alt er ati o n of C o n s e nt
Wai ver of c o nse nt is re q ueste d f or t he f oll o wi n g
Tele p h o ne scree ns.
E x plai n  w h y y o ur researc h ca n n ot be practica bl y carrie d o ut wit h o ut t he wai ver or alterati o n
It will be ver y i m practical f or o ur st u d y t o as k t o t he s u bjects t o c o me t o o ur office t o si g n a c o nse nt f or m 
a n d
t he n pr ocee d t o esta blis h if t he y are eli gi ble.
Descri be w het her a n d h o w s u bjects will be pr o vi de d wit h a d diti o nal perti ne nt i nf or mati o n after partici pati o n
N/ A
P er s o n s d e si g n at e d t o di s c u s s a n d d o c u m e nt c o n s e nt
Select t he na mes of pers o ns desi g nate d t o o btai n  c o nse nt/asse nt
Gir gis, Ra g y, M D
Ke geles, La wre nce, M D
K o orat h ota, S harat h
La uri ola, Vi nce nz o
Sl oa n, Ric har d, P H D
Stei n ber g, L o uisa, M D
Stella, C hl oe
U niac ke, Blair
T y pe i n t he na me(s) n ot f o u n d i n t he a b o ve list
St u d y Pr o c e d ur e s
Descri be t he pr oce d ures re q uire d f or t his st u d y
St u d y Pr ot oc ol S u m m ar y:
I ntereste d s u bjects will be scree ne d b y a st u d y c o or di nat or d uri n g a tele p h o ne call. T h ose w h o meet 
e nr oll me nt criteria will be sc he d ule d f or a n a p p oi nt me nt a n d pr o vi de i nf or me d c o nse nt. Partici pa nts' hei g ht, 
wei g ht, a n d bl o o d press ure will be meas ure d. T he y will be as ke d t o fill o ut t he Baec ke P h ysical Acti vit y 
Q uesti o n naire a n d a ns wer t he Ge neral Healt h Q uesti o n " H o w w o ul d y o u descri be y o ur ge neral healt h?". 
Ne xt, partici pa nts will be s h o w n a sa m ple of t he st u d y ca ps ules a n d as ke d “ Are y o u a ble t o s wall o w t his 
ca ps ule?” Partici pa nts a ns were d “ N o” will be e xcl u de d fr o m t he st u d y. T he M o ntreal C o g niti ve Assess me nt 

Pr ot oc ol S u m m ar y F or m
7 0 3 4
Sl oa n, Ric har d
P a g e 1 5 of 2 6
( M o C A) will als o be a d mi nistere d. If t he partici pa nt's sc ore is 2 6 p oi nts of hi g her, t he first 
ne ur o ps yc h ol o gical testi n g will be sc he d ule d. T his is a pre- baseli ne testi n g t o wear off a n y n o velt y effects. 
S u bjects will als o g o t hr o u g h a R u n-I n peri o d i n w hic h t he y will ta ke  place b o-c o ntai ni n g ca ps ules  f or t w o 
wee ks . T he n, t he first set of a p p oi nt me nts will be sc he d ule d w hic h c o nsists of a ne ur o ps yc h ol o gical testi n g 
sessi o n a n d a n M RI sca n ( o pti o nal). Partici pa nts' b o d y c o m p ositi o n will als o be meas ure d at t his ti me. 
S u bse q ue ntl y, t he y will be ra n d o mize d t o ta ke o ne of f o ur dail y i nta ke a m o u nts of c oc oa fla va n ol, 0 m g, 
2 2 5 m g, 4 0 0 m g or 6 5 0 m g, per da y f or 1 2 wee ks. S u bjects will be sc he d ule d f or o ne ne ur o ps yc h ol o gical 
sessi o ns after 4 wee ks of ta ki n g t he c oc oa fla va n ols. T he n at t he e n d of t he 1 2 wee k peri o d, t he sec o n d set 
of a p p oi nt me nts will be sc he d ule d ( Ne ur o ps yc h ol o gical Testi n g a n d t he o pti o nal M RI sca n). Partici pa nts' 
wei g ht a n d b o d y c o m p ositi o n will als o be meas ure d. Fi nall y, 8 wee ks after t he last i nta ke of c oc oa 
fla va n ols, partici pa nts will c o m plete a fi nal ne ur o ps yc h ol o gical testi n g sessi o n a n d a fi nal wei g ht a n d b o d y 
c o m p ositi o n meas ure me nts will be ta ke n. 
 
I niti al scree ni n g: 
S u bjects will be scree ne d b y a  st u d y c o or di nat or d uri n g a tele p h o ne call. T he tele p h o ne scree n i ncl u des 
me dical hist or y a n d diet q uesti o ns. T h ose w h o meet e nr oll me nt criteria will be sc he d ule d f or a n 
a p p oi nt me nt d uri n g w hic h t he st u d y will be descri be d i n detail, i nf or me d c o nse nt will be o btai ne d.
T he M o C A will be a d mi nistere d b y a trai ne d researc h assista nt after c o nse nt is o btai ne d b ut bef ore fi nal 
eli gi bilit y is deter mi ne d. T he R A will n ot i nf or m t he s u bject of t he res ult. If t he s u bject's sc ore is <  2 6 
(c ut off sc ore), t he R A will c o ntact t he st u d y’s ne ur o ps yc h ol o gist, Dr. A da m Bric k ma n t o disc uss t he res ults. 
T he R A will t he n i nf or m t he s u bject of i neli gi bilit y a n d will refer t he m t o Dr. A da m Bric k ma n t o disc uss t he 
sc ore if nee de d.
 
R u n-I n Peri o d: 
All partici pa nts will be  i nstr ucte d t o ta ke t w o place b o-c o ntai ni n g ca ps ules t wice a da y at meals f or t w o 
wee ks. T his is a wa y t o test c o m plia nce bef ore ra n d o mizati o n of s u bjects t o t he 1 2 wee ks test peri o d.  
 
At t he be gi n ni n g of t he R u n-I n Peri o d, partici pa nts will recei ve t he place b o-c o ntai ni n g ca ps ules i n a seale d 
H D P E b ottle, t o p pe d  wit h a n electr o nic Me dicati o n E ve nt M o nit ori n g S yste m ( M E M S) Ca p ma n ufact ure d 
b y M W V S witzerla n d Lt d. T he M E M S Ca p re gisters t he date a n d ti me t he b ottle is o pe ne d a n d cl ose d. T he 
researc h assista nt will e x plai n h o w t he de vice w or ks a n d will set u p a user pr ofile o n M E M S Ca p’s we bsite 
usi n g o nl y t he partici pa nt’s s u bject I D. At t he e n d of t he R u n-I n Peri o d, t he researc h assista nt will c ollect 
t he b ottle a n d ca p bac k fr o m t he partici pa nt a n d d o w nl oa d t he data usi n g a M E M S Ca p rea der a n d tra nsfer 
t he data t o M W V’s sec ure d ce ntralize d data base calle d me d A mi g o. 
T o a d dress a n y i nf or mati o n sec urit y c o ncer ns, t he pr ofile will o nl y use t he  partici pa nt’s s u bject I D t o pr otect 
t he partici pa nt’s i de ntit y. O nl y t he researc h assista nts will ha ve access t o t he partici pa nt’s pr ofile. I n t his 
wa y, we ca n m o nit or partici pa nts’ c o m plia nce t hr o u g h o ut t he st u d y.  
 
Partici pa nts will be e xcl u de d after  t he R u n-I n peri o d if t he y miss m ore t ha n 2 i nta ke occasi o ns o ut of 1 4 
da ys ( 2 8 occasi o ns t otal) meas ure d b y M E M S Ca p or if t here are m ore t ha n 8 ca ps ules left i n t he b ottle. 
 
O pti o n al M RI ( M a g netic Res o n a nce I m a gi n g) Pr oce d ures: 
P ote ntial s u bjects will be i nitiall y scree ne d  o n t he p h o ne b y trai ne d researc h assista nts f or M RI eli gi bilit y 
wit h a me dical hist or y q uesti o n naire t hat a d dresses M RI a n d ga d oli ni u m-relate d c o ntrai n dicati o ns (e. g. 

Pr ot oc ol S u m m ar y F or m
7 0 3 4
Sl oa n, Ric har d
P a g e 1 6 of 2 6
car diac pace ma ker, i nter nal p u m p,  ki d ne y disease, li ver disease, a n d a n y hist or y of aller gic reacti o ns t o 
me dicati o n.) Partici pa nts will be as ke d if t he y ha d a n y pre vi o us M RI sca n a n d a b o ut M RI-relate d 
i ntra ve n o us i njecti o ns wit h t he p ur p ose of c o ntrast a ge nt a d mi nistrati o n. I n t he case t hat partici pa nts recall 
a n I V t he y will be as ke d if t he c o ntrast a ge nt use d was Ga d oli ni u m. Partici pa nts wit h m ore t ha n o ne M RI 
sca n wit h t he use of Ga d oli ni u m will be e xcl u de d fr o m t he st u d y. 
Eli gi ble s u bjects will t he n c o me i n  f or a c o nse nt sessi o n wit h a researc h assista nt. T he s u bject will rea d 
t hr o u g h t he pri mar y c o nse nt f or m, w hic h c o ntai ns a brief o ver vie w of t he M RI pr oce d ure a n d ga d oli ni u m. 
T he s u bject will c o m plete a Pre- Ga d oli ni u m Assess me nt of Ris k f or m, w hic h will be re vie we d a n d si g ne d 
b y o ur st u d y p h ysicia n, Dr. Sc ott S mall. T he Pre- Ga d oli ni u m Assess me nt of Ris k f or m gat hers perti ne nt 
me dical i nf or mati o n i ncl u di n g a hist or y of ki d ne y or li ver disease, h y perse nsiti ve reacti o ns t o c o ntrast 
a ge nts or relate d aller ge ns. S u bjects w h o ha ve a n y M RI or ga d oli ni u m-relate d c o ntrai n dicati o ns will n ot be 
c o nsi dere d eli gi ble. Eli gi ble s u bjects w h o ha ve rea d t he c o nse nt f or m a n d c o m plete d t he Pre- Ga d oli ni u m 
Assess me nt of Ris k f or m will si g n a n d date t he c o nse nt f or m. S u bjects will als o c o m plete t he N Y S PI M RI 
Metal Scree ni n g q uesti o n naire. T he q uesti o n naire as ks s pecificall y a b o ut metallic i m pla nts a n d past 
e x perie nces wit h metal t o f urt her ascertai n a n y p ossi ble ris ks t he pers o n ma y i nc ur b y e nteri n g t he sca n ner. 
If a n y metallic i m pla nts are detecte d t hat are u ns uita ble f or t he sca n ner, t hat s u bject will n ot be i ncl u de d i n 
t his part of t he st u d y. 
T he M RI sca n uses a n e x o ge n o us c o ntrast a ge nt calle d ga d oli ni u m  w hic h i ncreases si g nal t o n oise rati o 
d uri n g M RI sca n ni n g all o wi n g i m pr o ve d i ma ge q ualit y. O n t he da y of t he pri mar y c o nse nt, s u bjects will be 
gi ve n a ga d oli ni u m fact s heet writte n b y Dr. Sc ott S mall. T he fact s heet i ncl u des a descri pti o n of t he t y pe of 
ga d oli ni u m we use a n d its p ossi ble si de effects a n d c o ntrai n dicati o ns. If s u bjects ha ve a n y q uesti o ns 
re gar di n g t he use of ga d oli ni u m, we will pr o vi de t he s u bjects wit h Dr. S mall's c o ntact i nf or mati o n. I n 
a d diti o n, t he y will be a ble t o as k q uesti o ns of t he re gistere d n urse, fell o w, or atte n di n g p h ysicia n w h o will 
a d mi nister t he ga d oli ni u m. 
 
O n t he da y of t he M RI, t he s u bject will meet wit h a re gistere d n urse, fell o w, or atte n di n g p h ysicia n w h o will 
pr o vi de t he s u bject  wit h a detaile d descri pti o n of t he M RI pr oce d ure i ncl u di n g t he use of t he c o ntrast a ge nt 
ga d oli ni u m, its p ossi ble si de effects a n d c o ntrai n dicati o ns.  T he s u bject will c o m plete a q uiz as a c hec k t hat 
t he s u bject f ull y u n dersta n ds t he use of ga d oli ni u m, p ossi ble si de effects a n d c o ntrai n dicati o ns. A re gistere d 
n urse, a n M D fell o w, t he atte n di n g p h ysicia n, or t he Direct or of t he M RI U nit, will t he n prese nt t he se parate 
c o nse nt f or m f or t he M RI a n d ga d oli ni u m a n d o btai n t he s u bject's si g nat ure i n pers o n. T he re gistere d n urse, 
fell o w, or atte n di n g p h ysicia n will re vie w b ot h t he M RI q uesti o n naire pri or t o sca n ni n g a n d t he res ults of 
t he creati ni ne test (see bel o w) pri or t o ga d oli ni u m i njecti o n. 
Bef ore t he M RI sca n is starte d, a  bl o o d sa m ple will be ta ke n a n d res ults f or ser u m creati ni ne le vel will be 
use d t o esti mate gl o mer ular filtrati o n rate (e G F R). Ser u m creati ni ne, al o n g wit h a ge, ge n der, a n d race will 
be use d t o deri ve a n esti mate d gl o mer ular filtrati o n rate acc or di n g t o a p u blis he d calc ulat or a vaila ble at 
htt p:// w w w. ne p hr o n.c o m/ M D R D _ G F R.c gi. A n y s u bject wit h a hist or y of re nal i m pair me nt or e G F R < 3 0 
m L/ mi n/ 1. 7 3 m 2 will be e xcl u de d fr o m recei vi n g a n i ntra ve n o us i njecti o n of t he c o m p o u n d ga d oli ni u m.
S u bjects wit h acce pta ble G F Rs will recei ve a n i ntra ve n o us i njecti o n of a Ga d oli ni u m c o m p o u n d, t o hel p 
vis ualize t he bl o o d s u p pl y t o t he brai n. Ga d oli ni u m c o m p o u n ds are c o ntrast a ge nts t hat diss ol ve i n bl o o d 
a n d are eli mi nate d b y t he ki d ne ys. T hese c o m p o u n ds are r o uti nel y use d as part of sta n dar d M RI tests acr oss 

Pr ot oc ol S u m m ar y F or m
7 0 3 4
Sl oa n, Ric har d
P a g e 1 7 of 2 6
t he w orl d a n d it has rare si de effects. We use t he macr oc yclic varia nt of Ga d oli ni u m, D otare m ( ga d o be nate 
me gl u mi ne), i n w hic h data s u g gest t hat u nli ke t he li near Ga d oli ni u m varia nt, t he macr oc ylic varia nt is n ot 
retai ne d i n t he brai n re gar dless of t he n u m ber of Ga d oli ni u m a d mi nistrati o ns. [ 1 6, 1 7]. Pe o ple wit h aller gies 
or k n o w n se nsiti vities t o c o ntrast a ge nts will n ot be i njecte d wit h ga d oli ni u m. 
F or fe male s u bjects o nl y: bef ore bei n g sca n ne d, t he y will be as ke d t o si g n a pre g na nc y test release f or m 
stati n g t he y ha ve bee n war ne d of p ote ntial ris k t o a n u n b or n c hil d/fet us a n d ha ve bee n offere d a pre g na nc y 
test t o deter mi ne if t he y are pre g na nt bef ore bei n g sca n ne d a n d ha ve c h ose n t o decli ne. Beca use t he 
recr uiti n g a ge ra n ge is 5 0- 7 5 years ol d a n d we ha ve scree ne d f or p ost- me n o pa usal a n d pre g na nc y stat us, we 
will n ot re q uire e ver y fe male s u bject t o ta ke a pre g na nc y test. F or s u bjects w h o ref use d t o si g n t he release 
f or m, pre g na nc y tests will be pr o vi de d a n d t he re gistere d n urse, fell o w, or atte n di n g p h ysicia n will si g n off 
o n t he res ults of t he pre g na nc y test.
 
M RI sca ns will be ac q uire d at t w o ti me p oi nts: baseli ne a n d f oll o wi n g t he 1 2- wee k c oc oa c o ns u m pti o n 
peri o d. S u bjects  will be as ke d t o c o ns u me t heir last c oc oa fla va n ol ca ps ules bet wee n 1 2 a n d 2 4 h o urs pri or 
t o t he sc he d ule d f oll o w- u p M RI sca n. 
O ne of t he mai n a d va nta ges of M RI is  t hat patie nts a n d s u bjects ca n be safel y i ma ge d re peate dl y o ver ti me. 
T his is tr ue als o f or ga d oli ni u m e n ha nce d M RI, as use d i n o ur pr ot oc ol (f or e xa m ple, Filli p pi et al. Brai n, 
1 9 9 8, 1 2 1: 2 0 1 1- 2 0 2 0). T o detect a c ha n ge i n C B V ca use d b y ne ur o ge nesis usi n g M RI, i ma ges m ust be 
ac q uire d b ot h bef ore a n d after e x p os ure t o a ne ur o ge nic sti m ula nt – i n t his case, fla va n ols. T heref ore, 
s u bjects e nr olle d will be i ma ge d t wice, o nce i m me diatel y pri or t o t he start of t he dietar y fla va n ols a n d o nce 
i m me diatel y f oll o wi n g t he last c o ns u m pti o n of c oc oa fla va n ols. I n a d diti o n t o t he ga d oli ni u m sca n, sta n dar d 
M RI se q ue nces will be ac q uire d, s uc h as 3 D T 1- wei g hte d hi g h-res ol uti o n a nat o mical i ma ges, fl ui d 
atte n uate d i n verse rec o ver y ( F L AI R) T 2- wei g hte d sca ns, a n d a diff usi o n te ns or i ma gi n g sca n ( D TI) use d t o 
trac k t he m oti o n of water wit hi n a v o xel.  
 
O n t he da y of t he M RI, if t he s u bject d oes n ot  wa nt t o recei ve ga d oli ni u m, we will as k t he s u bject if t he y are 
willi n g t o ha ve t he M RI sca n wit h o ut t he c o ntrast a ge nt. T he se q ue nces we will ac q uire d will be t he T 1-
wei g hte d hi g h-res ol uti o n a nat o mical i ma ges, fl ui d atte n uate d i n verse rec o ver y ( F L AI R) T 2- wei g hte d sca ns, 
a n d a diff usi o n te ns or i ma gi n g sca n ( D TI).  
T he M RI sca ns will be se nt t o a ne ur ora di ol o gist t o be e xa mi ne d f or e vi de nce of a n y a b n or malities wit hi n 1 
m o nt h of t he sca n. Letters will be distri b ute d t o all partici pa nts f oll o wi n g eac h sca n i n dicati n g t he 
si g nifica nt, i nsi g nifica nt, or mi n or fi n di n gs. C o pies of t he M RI Re p ort ca n be se nt t o t he partici pa nt’s 
p h ysicia n if re q ueste d. If t he cli nical rea di n g s u g gests e vi de nce of si g nifica nt a b n or malities (at t he 
discreti o n of t he ra di ol o gist), t he PI will be n otifie d i m me diatel y, a n d fee d bac k will be pr o vi de d t o t he 
partici pa nt. 
 
N Y S PI M RI U nit S afet y M o nit ori n g Pr oce d ures
A n M D or R N, w h o has bee n a p pr o ve d b y Dr. La wre nce Ke geles, t he  Me dical Direct or of t he N Y S PI M RI 
U nit, will be c o veri n g eac h sca n t o m o nit or partici pa nts f or seri o us aller gic reacti o n. T he c o veri n g M D/ R N 
will be B L S certifie d a n d will be trai ne d i n t he use of a n e pi ne p hri ne a ut o-i nject or (“e pi pe n”). A n e pi pe n 
will be pr o vi de d b y t he M RI u nit a n d ke pt o n t he u nit. 

Pr ot oc ol S u m m ar y F or m
7 0 3 4
Sl oa n, Ric har d
P a g e 1 8 of 2 6
T he st u d y staff will als o prese nt a ga d oli ni u m st u d y  f or m t o t he c o veri n g M D/ R N. T he c o veri n g M D/ R N 
will verif y t hat t he s u bject meets t he creati ni ne cleara nce i ncl usi o n criteri o n a n d will e xcl u de s u bjects w h o 
d o n ot or f or w h o m t he c o m plete d ga d oli ni u m f or m is n ot prese nte d. F or s u bjects w h o meet eli gi bilit y 
criteria, t he c o veri n g M D/ R N will place a n I V cat heter wit h t-c o n nect or bef ore t he sca n a n d re m o ve t he 
cat heter f oll o wi n g t he e n d of t he sca n. 
T he partici pa nt’s wei g ht will be meas ure d a n d c o m m u nicate d t o t he c o veri n g M D/ R N a n d M RI 
tec h n ol o gist. T he M RI tec h n ol o gist will use t his i nf or mati o n t o deter mi ne t he v ol u me d ose of ga d oli ni u m 
s ol uti o n a n d verif y t he d ose wit h t he c o veri n g M D/ R N pri or t o pre pari n g it. 
T he c o veri n g M D/ R N will be prese nt at t he ti me of ga d oli ni u m i njecti o n a n d will m o nit or t he partici pa nt 
be gi n ni n g at least 5 mi n utes pri or t o t he ti me of i njecti o n u ntil at least 1 0 mi n utes f oll o wi n g i njecti o n.
I n case of E mer ge nc y, t he c o veri n g M D/ R N will a d mi nister e pi ne p hri ne via e pi pe n if i n dicate d a n d pr o vi de 
s u p p orti ve care as i n dicate d i ncl u di n g C P R a n d o x y ge n u ntil arri val of e mer ge nc y res p o nse pers o n nel.
I n case of a n arrest t he M RI u nit staff will call 
• t he N Y S PI ra pi d res p o nse tea m 
• t he N Y P H c o de tea m 
• 9 1 1t he M RI u nit direct or a n d me dical direct or
I n case of a n arrest M RI u nit staff will dise n ga ge t he M RI sca n ner be d a n d m o ve t he partici pa nt o n t he 
sca n ner be d o ut of t he sca n ner r o o m. M RI u nit staff will tra ns p ort t he base me nt le vel cras h cart t o t he M RI 
u nit.
I n case of res ol uti o n of t he e mer ge nc y (e. g. e mesis i n t he sca n ner) t he st u d y ma y res u me.
 
 
Ne ur o ps yc h ol o gic al Testi n g:
A sta n dar dize d batter y of c o m p uterize d a n d  pe ncil-a n d- pa per ne ur o ps yc h ol o gical tests will be a d mi nistere d 
t o meas ure o verall c o g niti ve f u ncti o ni n g a n d c ha n ge i n c o g niti o n. We will use t hree me m or y tests as 
pri mar y o utc o me meas ures. O ne is a serial list lear ni n g a n d me m or y tas k a n d t he ot her t w o are 
c o m p uterize d me m or y a n d c o g niti o n tas ks. T he e ntire batter y of tests ta kes a p pr o xi matel y 1 h o ur t o 
c o m plete. 
 
T hese are all sta n dar dize d tests c o m m o nl y use d i n cli nical practice. Gr oss c o g niti ve f u ncti o n  a n d 
i ntelli ge nce meas ures will be a d mi nistere d at baseli ne o nl y. All ot her meas ures will be gi ve n at all testi n g 
visits; alter nate f or ms will be use d w here a p plica ble.  
 
R a n d o miz ati o n:
S u bjects w h o c o m plete/ ne ur o ps yc h ol o gical testi n gs a n d t he M RI ( o pti o nal) will be  ra n d o mize d t o o ne of  
f o ur gr o u ps, t he me m bers of w hic h will be assi g ne d a s pecific dail y c oc oa fla va n ol i nta ke a m o u nt ( 0 m g, 
2 2 5 m g, 4 0 0 m g, or 6 5 0 m g per da y), res pecti vel y.
 
Diet ar y I nter ve nti o n:

Pr ot oc ol S u m m ar y F or m
7 0 3 4
Sl oa n, Ric har d
P a g e 1 9 of 2 6
Dail y, eac h s u bject will c o ns u me eit her t w o c oc oa fla va n ol-c o ntai ni n g ca ps ules t wice a da y wit h a  meal or 
t w o place b o-c o ntai ni n g ca ps ules t wice a da y wit h a meal. T he ca ps ule material f or b ot h t y pes of ca ps ule is 
i de ntical a n d gelati n- base d. All test materials are f o o d- gra de materials, ma n ufact ure d a n d pac ka ge d u n der 
c urre nt G o o d Ma n ufact uri n g Practices, or c G M P.
T he c oc oa fla va n ol-c o ntai ni n g ca ps ules are f or m ulate d t o pr o vi de a t otal of 0 m g, 2 2 5 m g, 4 0 0 m g, or 6 5 0 
m g of c oc oa  fla va n ols per 4-ca ps ule ser vi n g. Eac h ca ps ule c o ntai ns 5- 1 6 m g of caffei ne, de pe n di n g o n dail y 
i nta ke of c oc oa fla va n ols. S u bjects will be ra n d o mize d i nt o o ne of f o ur gr o u ps, t he me m bers of w hic h will 
be assi g ne d a s pecific dail y c oc oa fla va n ol i nta ke a m o u nt.
a. 0 m g c oc oa fla va n ol-free c o ntr ol ca ps ules :
I n gre die nts: micr ocr ystalli ne cell ul ose, gelati n, artificial c ol ori n g, ma g nesi u m stearate, stearic aci d, silica, 
a n d tita ni u m di o xi de.
b. 2 2 5 m g c oc oa fla va n ol ca ps ules:
I n gre die nts: C oc oa pr o ™ c oc oa e xtract, micr ocr ystalli ne cell ul ose, gelati n, stearic aci d, silica, 
cr oscar mell ose s o di u m, ma g nesi u m stearate a n d tita ni u m di o xi de.
c. 4 0 0 m g c oc oa fla va n ol ca ps ules:
I n gre die nts: C oc oa pr o ™ c oc oa e xtract, micr ocr ystalli ne cell ul ose, gelati n, stearic aci d, silica, 
cr oscar mell ose s o di u m, ma g nesi u m stearate a n d tita ni u m di o xi de.
d. 6 5 0 m g c oc oa fla va n ol ca ps ules:
I n gre die nts: C oc oa pr o ™ c oc oa e xtract, micr ocr ystalli ne cell ul ose, gelati n, stearic aci d, silica, 
cr oscar mell ose s o di u m, ma g nesi u m stearate a n d tita ni u m di o xi de.
 
F o o d S afet y
B ot h, t he c oc oa fla va n ol-c o ntai ni n g ca ps ules  a n d t he place b o-c o ntai ni n g ca ps ules will be pr o vi de d b y 
M A R S I nc., U S A.  M A R S I nc. is a U S D A-lice nse d f o o d ma n ufact urer a n d all test materials are f o o d- gra de 
materials, ma n ufact ure d a n d pac ka ge d u n der c urre nt G o o d Ma n ufact uri n g Practices, or c G M P. 
Q u alit y C o ntr ol/ A d here nce
Virt uall y all st u dies s uffer fr o m s u bsta ntial attriti o n. T o  hel p mai ntai n partici pa nt rete nti o n, t he f oll o wi n g 
acti vities will be i m ple me nte d: 
C o m pli a nce M o nit ori n g:
T he M E M S Ca p use d d uri n g t he R u n-I n Peri o d  will als o be use d d uri n g t he 1 2 wee ks of
i nter ve nti o n t o m o nit or c o m plia nce. Partici pa nts will als o be as ke d t o fill o ut a dail y i nta ke re p ort f or m 
e ver y ti me t he y ta ke t he ca ps ules t o kee p trac k of t heir r o uti ne. 
T he Rese arc h Assist a nts ( R A) :
A researc h assista nt is assi g ne d t o  eac h s u bject after c o nse nt. T he R A will be trai ne d i n be ha vi oral 
tec h ni q ues desi g ne d t o pr o m ote a d here nce, i ncl u di n g wee kl y p h o ne or e mail c o ntact t o re mi n d a n d t o 
e nc o ura ge t he c o ns u m pti o n of t he c oc oa fla va n ols. T he R A will f oll o w s u bjects t hr o u g h o ut t he pr ot oc ol, 
letti n g t he m k n o w w he n it is ti me t o sc he d ule testi n g sessi o ns. T he R A will meet wit h t he s u bject at eac h 
testi n g sessi o n t o e x plai n t he pr oce d ure a n d t o c ollect dail y i nta ke re p ort f or ms.
I m a gi n g D at a Ac q uisiti o n f or t he O pti o n al M RI s u b-st u d y:
Usi n g a P hili ps  3. 0 Tesla sca n ner, T 1 wei g hte d i ma ges ( T R, 2 0 m g; T E, 6 m g; fli p a n gle, 2 5 de grees; i n pla ne 
res ol uti o n, 0. 8 6 m m/ 0. 8 6 m m; slice t hic k ness 3 m m) will be ac q uire d per pe n dic ular t o t he hi p p oca m pal 
l o n ga xis bef ore a n d 4 mi n. after i. v. a d mi nistrati o n of t he c o ntrast a ge nt ga d oli ni u m ( 0. 1 m m ol/ k g). T o 
ge nerate C B V ma ps, t he prec o ntrast i ma ge will s u btracte d fr o m t he p ostc o ntrast i ma ge, a n d t he differe nce 
i n t he sa gittal si n us, w hic h ser ves as a n esti mate of t he i ma ge i nte nsit y c ha n ge of 1 0 0 % bl o o d, will be 

Pr ot oc ol S u m m ar y F or m
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rec or de d. T he s u btracte d i ma ge will t he n be di vi de d b y t he differe nce i n t he t o p % of t he pi xels meas ure d 
fr o m t he sa gittal si n us a n d m ulti plie d b y 1 0 0, yiel di n g relati ve C B V ma ps.
 
I n a d diti o n t o t he ga d oli ni u m sca n, sta n dar d M RI se q ue nces will be ac q uire d, s uc h as 3 D T 1- wei g hte d hi g h-
res ol uti o n a nat o mical i ma ges, fl ui d atte n uate d i n verse rec o ver y ( F L AI R) T 2- wei g hte d sca ns, a n d a diff usi o n 
te ns or i ma gi n g sca n ( D TI) use d t o trac k t he m oti o n of water wit hi n a v o xel.  
 
Me dic al M o nit or:
We’ ve i de ntifie d Dr. Peter S ha pir o, Pr ofess or of Ps yc hiatr y  a n d Ass ociate Direct or of C o ns ultati o n- Liais o n 
Ps yc hiatr y Ser vice & Be ha vi oral Me dici ne, as t he Me dical M o nit or of t he st u d y. Alt h o u g h t he i nter ve nti o n 
ca ps ules t he msel ves are e x pecte d t o p ose l o w ris k, t he i nter ve nti o n c oc oa fla va n ol le vels are d o u ble bli n de d 
fr o m all st u d y staff a n d i n vesti gat ors. As a res ult, we are i ncl u di n g a m o nit or w h o will ha ve access t o t he 
bli n de d treat me nt le vels i nf or mati o n a n d will i n de pe n de ntl y re p ort t o t he I R B i n t he e ve nt of u ne x pecte d 
s y m pt o ms or me dical c o n diti o ns d uri n g i n di vi d uals’ partici pati o n i n t he st u d y. T he Me dical M o nit or is 
res p o nsi ble f or o verseei n g t he safet y of t he researc h a n d re p ort o bser vati o ns/fi n di n gs t o t he I R B of Rec or d. 
He will re vie w all u na ntici pate d pr o ble ms i n v ol vi n g ris k t o partici pa nts or ot hers ass ociate d wit h t he 
pr ot oc ol a n d pr o vi de a n u n biase d writte n re p ort of t he e ve nt t o t he I R B of Rec or d. T he Me dical M o nit or 
ma y disc uss t he researc h pr ot oc ol wit h t he i n vesti gat ors, i nter vie w h u ma n s u bjects, a n d c o ns ult wit h ot hers 
o utsi de of t he st u d y a b o ut t he researc h. T he Researc h M o nit or s hall ha ve a ut h orit y t o st o p t he researc h 
pr ot oc ol i n pr o gress, re m o ve i n di vi d ual h u ma n s u bjects fr o m t he st u d y, a n d ta ke w hate ver ste ps are 
necessar y t o pr otect t he safet y a n d well- bei n g of h u ma n s u bjects u ntil t he I R B ca n assess t he m o nit or's 
re p ort. T he Me dical M o nit or is res p o nsi ble f or pr o m ptl y re p orti n g t heir o bser vati o ns a n d fi n di n gs t o t he 
I R B.
 
Te xt Mess a ge Re mi n ders: 
I n or der t o i ncrease c o m plia nce i n bet wee n st u d y visits, partici pa nts will recei ve te xt messa ge re mi n ders t hat 
will be  se nt t hr o u g h o ur pass w or d- pr otecte d data base. T he data base will be pr o gra m me d t o a ut o maticall y 
se n d te xt messa ges t o s u bjects’ m o biles p h o nes at s pecifie d ti mes via Re mi n der Ser vices I nc. Re mi n der 
Ser vices I nc. is a n a p pr o ve d C ol u m bia ve n d or a n d has si g ne d a B usi ness Ass ociate A gree me nt wit h C U M C 
Pri vac y Officer. N o pers o nall y i de ntifia ble i nf or mati o n will be se nt t o Re mi n der Ser vices I nc. T he te xt 
messa ges will re mi n d s u bjects of st u d y visit a p p oi nt me nts a n d re mi n ders t o c o m plete q uesti o n naires. T he 
messa ge will pr o m pt s u bjects t o re pl y wit h a n u m ber a ns wer i n dicati n g w het her t he y c o nfir m or nee d t o 
resc he d ule t he a p p oi nt me nt. If s u bjects i n dicate t hat t he y nee d t o resc he d ule, researc h assista nts will c o ntact 
s u bjects directl y t o resc he d ule t he a p p oi nt me nts. T he nat ure of t he st u d y will n ot be re veale d n or will a n y 
as pect of t he st u d y pr oce d ures be disc usse d t hr o u g h te xt messa ges. Partici pa nts ma y c h o ose t o o pt i n or o pt 
o ut of t he te xt messa ge re mi n ders at a n y ti me t hr o u g h o ut t he st u d y.  
Y o u ca n u pl oa d c harts or dia gra ms if a n y
Bl o o d a n d ot h er Bi ol o gi c al S a m pl e s
Please create  or i nsert a ta ble descri bi n g t he pr o p ose d c ollecti o n of bl o o d or ot her bi ol o gical s peci me ns

Pr ot oc ol S u m m ar y F or m
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P a g e 2 1 of 2 6
A bl o o d sa m ple of 4 1 ml will  be ta ke n pri or t o a n d after c o m pleti o n of t he dietar y i nter ve nti o ns. Bl o o d will 
be dra w n at t he M RI sca n bef ore t he 1 2 wee k c o ns u m pti o n peri o d, after t he 1 2 wee k peri o d a n d t he n 8 
wee ks after t he c oc oa fla va n ol was h o ut peri o d. 
 
If ti me c o nstrai nts pre ve nt bl o o d c ollecti o n at eit her sca n, q ualifie d researc h staff ma y c ollect t he sa m ples at 
a se parate sessi o n. 
T he ta ble bel o w i n dicates t he p ur p ose of t he bl o o d dra w. 
Ass a ys: ( 4 1 ml t ot al)
P ur p ose
Creati ni ne
C o nfir m ki d ne y f u ncti o n
H or m o nes ( F S H, pr o gester o ne, 
estra di ol, test oster o ne &  A nti-
M ulleria n H or m o ne)
T o o bser ve h or m o nal effects of t he i nter ve nti o n. 
C C L 1 1
Deter mi ne relati o ns hi p t o de ntate g yr us f u ncti o n  
T he o br o mi ne
C o nfir m c o m plia nce 
I nfla m mat or y mar kers 
(I L 6, T N F, C R P, & H M G B 1)
Deter mi ne relati o n of t he i nter ve nti o ns t o  t he effect of 
i nfla m mati o n o n healt h.
Meta b olis m
C hec k f or n or mal meta b olis m b y l o o ki n g at fasti n g gl uc ose  
a n d i ns uli n le vels
A s s e s s m e nt I n str u m e nt s
Create a ta ble or gi ve a brief descri pti o n of t he i nstr u me nts  t hat will be use d f or assess me nt
Scree ni n g ( 3 0 mi n utes):  S u bject will c o m plete t he M o ntreal C o g niti ve Assess me nt ( M o C A) t o c hec k gr oss 
c o g niti ve a bilit y.
 
B aec ke P h ysic al Acti vit y q uesti o n n aire ( 1 0 mi n utes): I n o ur pre vi o us st u d y, we use d t his q uesti o n naire as 
a meas ure of se de ntar y acti vit y. We  wa nt t o kee p t his as a meas ure me nt t o c o m pare p h ysical acti vit y a m o n g 
s u bjects. 
 
Wei g ht, B o d y C o m p ositi o n ( 5 mi n utes):  T o assess t he B MI a n d b o d y c o m p ositi o n of all s u bjects, we will 
perf or m bi oelectrical i m pe da nce a nal ysis ( BI A). BI A will be c o n d ucte d wit h a b o d y fat a nal yzer ( B o d ystat 
1 5 0 0, Vac u me d, Ve nt ura Calif or nia) b y a p pl yi n g a c o nsta nt l o w le vel alter nati n g electrical c urre nt t o t he 
i n di vi d ual via electr o des o n a scale t hat s u bjects ste p o n.
 
Ne ur o ps yc h ol o gic al b atter y ( 1 h o ur) : A sta n dar dize d batter y of c o m p uterize d ne ur o ps yc h ol o gical tests 
will be a d mi nistere d t o meas ure o verall c o g niti ve f u ncti o ni n g a n d  c ha n ge i n c o g niti o n. We will use t hree 
me m or y tests as pri mar y o utc o me meas ures. O ne is a serial list lear ni n g a n d me m or y tas k a n d t he ot her t w o 
are c o m p uterize d me m or y a n d c o g niti o n tas ks.  T he e ntire batter y of tests ta kes a p pr o xi matel y 1 h o ur t o 
c o m plete. Bel o w is a descri pti o n of eac h batter y. 
 

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M o d Be nt
T he M o d Be nt is a n o bject rec o g niti o n  tas k wit h i m me diate matc hi n g trials a n d dela ye d rec o g niti o n trials. 
T he sti m uli use d i n t he M o d Be nt are i ntersecti n g si n us oi dal c ur ves desi g ne d para metricall y t o be si milar t o 
eac h ot her i n or der t o e v o ke t he patter n se parati o n c o g niti ve o perati o n. D uri n g t he i m me diate matc hi n g 
trials, partici pa nts vie w a si n gle c o m ple x sti m ul us f or 1 0 sec o n ds; f oll o wi n g a 1 sec o n d dela y t he y are as ke d 
t o select w hic h o ne of t w o o bjects is i de ntical t o t he st u die d sti m ul us. F oll o wi n g 4 1 matc hi n g trials, 
partici pa nts are s h o w n seriall y i n di vi d ual c o m ple x o bjects a n d as ke d t o i n dicate w het her t he o bject is 
i de ntical t o a n y of t he tar get sti m uli st u die d d uri n g t he i m me diate matc hi n g trials. T here are 8 2 rec o g niti o n 
trials, w hic h i ncl u de 4 1 tar gets a n d 4 1 f oils. T he pri mar y de pe n de nt varia ble f or t he M o d Be nt is t he mea n 
reacti o n ti me ( ms) f or c orrect rejecti o ns of f oil sti m uli o n t he dela ye d rec o g niti o n trials. Gi ve n t he pre vi o us 
o bser vati o n t hat perf or ma nce o n t he Be nt o n Vis ual Rec o g niti o n Test ( B V R T) is selecti vel y c orrelate d wit h 
f u ncti o ni n g of t he D G a n d t hat t he p utati ve r ole of D G i n patter n se parati o n, t he M o d Be nt was desi g ne d 
s pecificall y t o ma xi mize t he c o g niti ve o perati o n of patter n se parati o n a n d ta p D G f u ncti o ni n g.
 
NI H T o ol b o x
Acc or di n g t o t he NI H T o ol b o x we bsite: “ NI H T o ol b o x is a m ulti di me nsi o nal set of brief meas ures assessi n g 
c o g niti ve, e m oti o nal, m ot or a n d se ns or y f u ncti o n fr o m a ges 3 t o 8 5, meeti n g t he nee d f or a sta n dar d set of 
meas ures t hat ca n be use d as a “c o m m o n c urre nc y” acr oss di verse st u d y desi g ns a n d setti n gs. NI H T o ol b o x 
m o nit ors ne ur ol o gical a n d be ha vi oral f u ncti o n o ver ti me, a n d meas ures t he d o mai n c o nstr ucts acr oss 
de vel o p me ntal sta ges. T his facilitates t he st u d y of f u ncti o nal c ha n ges acr oss t he lifes pa n, i ncl u di n g 
e val uati n g i nter ve nti o n a n d treat me nt effecti ve ness.”
 
Ne ur o- Q o L
Acc or di n g t o t he Ne ur o- Q o L we bsite:  “ Ne ur o- Q o L is a set of self-re p ort meas ures t hat assesses t he healt h-
relate d q ualit y of life ( H R Q O L) of a d ults a n d c hil dre n wit h ne ur ol o gical dis or ders. Ne ur o- Q o L is c o m prise d 
of ite m ba n ks a n d scales t hat e val uate s y m pt o ms, c o ncer ns, a n d iss ues t hat are rele va nt acr oss dis or ders - 
al o n g wit h meas ures t hat assess areas m ost rele va nt f or s pecific patie nt p o p ulati o ns.”
T hese are all sta n dar dize d tests c o m m o nl y use d i n cli nical practice. Gr oss c o g niti ve f u ncti o n  a n d 
i ntelli ge nce meas ures will be a d mi nistere d at baseli ne o nl y. All ot her meas ures will be gi ve n at b ot h testi n g 
visits; alter nate f or ms will be use d w here a p plica ble. 
Q uesti o n n aire ( 3 0 mi n utes):  F o o d Fre q ue nc y Q uesti o n naire.
 
Please attac h c o pies, u nless sta n dar d i nstr u me nts are  use d
R e s e ar c h R el at e d D el a y t o Tr e at m e nt
Will researc h pr oce d ures res ult i n a dela y t o treat me nt?
N o
Treat me nt t o be  pr o vi de d at t he e n d of t he st u d y
N ot A p plica ble- N ot a Cli nical Treat me nt St u d y.

Pr ot oc ol S u m m ar y F or m
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P a g e 2 3 of 2 6
Ri s k s/ Di s c o mf ort s/I n c o n v e ni e n c e s 
Ris ks t hat c o ul d be e nc o u ntere d d uri n g t he st u d y peri o d
T here are  n o k n o w n ris ks t o t he o pti o nal M RI pr oce d ures. S o me i n di vi d uals e x perie nce cla ustr o p h o bia d ue 
t o c o nfi ne me nt of t he hea d i n a s mall s pace. T hese s u bjects will si m pl y disc o nti n ue t he st u d y. Si milarl y 
s o me mi g ht e x perie nce bac k pai n fr o m l yi n g o n t heir bac ks f or e xte n de d peri o ds of ti me. 
D uri n g ne ur o ps yc h ol o gical testi n g, s o me s u bjects mi g ht e x perie nce s o me disc o mf ort i n perf or mi n g s o me of 
t he pr o p ose d c o g niti ve tas ks i n t hat t he y mi g ht be e x perie nce d as t o o c halle n gi n g or fr ustrati n g.
T here are n o k n o w n ris ks t o c oc oa fla va n ol i nta ke at t he i nta ke le vels i n vesti gate d i n t his st u d y. A rece nt 
st u d y[ 1 5] re p orte d t he f oll o wi n g i n a trial usi n g dia betic patie nts: 
“ N o si de effects s uc h as hea dac hes, dizzi ness, s ki n e xa nt he ms, altere d b o wel ha bits, bl oati n g, na usea, 
v o miti n g, diarr hea, or car diac a d verse e ve nts, s uc h as w orse ni n g of Ca na dia n Car di o vasc ular S ociet y or 
Ne w Y or k Heart Ass ociati o n f u ncti o nal class, m y ocar dial i nfarcti o n, nee d f or perc uta ne o us c or o nar y 
i nter ve nti o n a n d b y pass s ur ger y were o bser ve d d uri n g t he e ntire d urati o n of t he trial.”[ 1 5]
Eac h s u bject will be as ke d f or c o nse nt t o pr o vi de a bl o o d sa m ple t o c o nfir m me n o pa usal  stat us. Bl o o d will 
als o be dra w n f or sta n dar d me dical scree ni n g tests. Bl o o d will be dra w n b y a lice nse d n urse, d oct or or 
p hle b ot o mist. Ris ks i n v ol ve t he p ossi bilit y of e x perie nci n g sli g ht pai n d ue t o t he bl o o d test. T here will 
li kel y be pai n o n i nserti o n of t he nee dle i nt o t he vei n, a n d t here mi g ht be sli g ht br uisi n g at t he s p ot w here 
t he bl o o d was o btai ne d.
 
Descri be pr oce d ures f or mi ni mizi n g ris ks
T o  mi ni mize ris ks d uri n g o pti o nal M RI pr oce d ures, s u bjects will be scree ne d caref ull y f or c o ntrai n dicati o ns 
t o M RI (e. g., metal i m pla nts) a n d e xcl u de d fr o m t he st u d y. Si milarl y, s o me mi g ht e x perie nce bac k pai n 
fr o m l yi n g o n t heir bac ks f or e xte n de d peri o ds of ti me. T hese i n di vi d uals will si m pl y disc o nti n ue t he st u d y. 
F oll o wi n g eac h sca n ni n g sessi o n, eac h partici pa nt’s str uct ural sca n is re vie we d b y a ne ur ora di ol o gist. 
A n y iss ue of me dical c o ncer n is br o u g ht t o t he partici pa nt’s atte nti o n i m me diatel y, a n d hel p is offere d i n 
o btai ni n g t he a p pr o priate referrals t o e val uate a n d p ote ntiall y treat a n y me dical c o n diti o n. Si milarl y, if a 
partici pa nt e x perie nces a n y ps yc h ol o gical distress s urr o u n di n g sca n res ults, a p pr o priate c o u nseli n g or 
referrals will be offere d. Dr. Sl oa n will c o or di nate t he referral pr ocess.
T o mi ni mize disc o mf ort i n s o me of t he pr o p ose d c o g niti ve tas ks t here is caref ul desi g n a n d prese ntati o n of 
t hese t hat mi ni mize t his ris k. S u bjects ha ve t he o pti o n of disc o nti n ui n g partici pati o n if t heir disc o mf ort 
bec o mes i nt olera ble. I n t hese rare sit uati o ns, Dr. Sl oa n pers o nall y meets wit h t he partici pa nt t o assess 
p ote ntial f u ncti o nal i m plicati o ns of t he test res ults. Base d o n t his assess me nt, a decisi o n is ma de a b o ut 
w het her t o s u g gest f urt her cli nical e val uati o n a n d a p pr o priate referrals are offere d.
We will ta ke e ver y preca uti o n t o mi ni mize disc o mf ort w he n o btai ni n g bl o o d. If t here is a n y diffic ult y i n 
o btai ni n g t he bl o o d or if t here is s o me me dical reas o n w h y t he s u bject ca n n ot all o w us t o perf or m t he bl o o d 
test, t he s u bject will si m pl y disc o nti n ue t he st u d y. 

Pr ot oc ol S u m m ar y F or m
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P a g e 2 4 of 2 6
M et h o d s t o Pr ot e ct C o nfi d e nti alit y
Descri be met h o ds t o pr otect  c o nfi de ntialit y
I n t he i nf or me d c o nse nt f or m, s u bjects are t ol d t hat t he i nf or mati o n t he y pr o vi de a n d all fi n di n gs will be 
ke pt strictl y c o nfi de ntial, wit h access li mite d t o t he researc h staff a n d t he p ossi ble e xce pti o n of state or 
fe deral re g ulat or y pers o n nel. N o o ne b ut desi g nate d pr oject staff will ha ve access t o t he master list li n ki n g 
s u bjects’ na mes t o c o de n u m bers, a n d all i nf or mati o n o btai ne d will be c o de d. Data will be a nal yze d wit h o ut 
refere nce t o pers o nal i de ntif yi n g i nf or mati o n, a n d t his i nf or mati o n will be caref ull y pr otecte d wit hi n t he 
data base. All pa per files will be ke pt i n l oc ke d file ca bi nets. 
O pti o n al M RI s u b-st u d y
M RI res ults (i ncl u di n g sca n i ma ges a n d acc o m pa n yi n g data) will be st ore d i n t he Pr o gra m f or I ma gi n g a n d 
C o g niti ve Scie nces data base at t he C ol u m bia U ni versit y Me dical Ce nter a n d accessi ble o nl y t o t he me m bers 
of t he researc h tea m. M RI re p orts (i ncl u di n g t he res ults of t he cli nical rea di n g) will be de-i de ntifie d a n d 
st ore d i n a l oc ke d file ca bi net i n t he office of Dr. Ric har d Sl oa n, Direct or of t he Be ha vi oral Me dici ne 
Pr o gra m at t he C ol u m bia U ni versit y Me dical Ce nter. 
Will t he st u dy be c o n d ucte d u n der a certific ate of c o nfi de nti ality ?
N o
Dir e ct B e n efit s t o S u bj e ct s  
Direct Be nefits t o S u bjects
S u bjects  will n ot directl y be nefit fr o m partici pati n g i n t he st u d y. 
C o m p e n s ati o n a n d/ or R ei m b ur s e m e nt 
Will c o m pe nsati o n or rei m b urse me nt f or e x pe nses be offere d  t o s u bjects?
Yes
Please descri be a n d i n dicate t otal a m o u nt a n d sc he d ule of pa y me nt(s). 
I ncl u de j ustificati o n f or c o m pe nsati o n a m o u nts a n d i n dicate if t here are b o n us pa y me nts.
C o m pe ns ati o n a n d Tr a vel Rei m b urse me nt 
S u bjects will be pai d $ 4 0 f or eac h of t he  fi ve ne ur o ps yc h ol o gical testi n g sessi o ns f or a t otal of $ 2 0 0. If 
s u bjects are 9 0 % a d here nt t o ca ps ule c o ns u m pti o n a n d c o m plete all e val uati o ns at t he e n d of t he st u d y, 
s u bjects will recei ve $ 5 0 b o n us f or a p ossi ble t otal of $ 2 5 0. 
 
If s u bjects a gree t o partici pate i n t he M RI s u b-st u d y, t he y will be pai d $ 7 0 f or eac h of t he t w o M RI sca ns. If 
s u bjects are 9 0 % a d here nt t o ca ps ule c o ns u m pti o n a n d c o m plete all e val uati o ns at t he e n d of t he st u d y, 
s u bjects will recei ve $ 6 0 b o n us f or a p ossi ble t otal of $ 2 0 0.
 

Pr ot oc ol S u m m ar y F or m
7 0 3 4
Sl oa n, Ric har d
P a g e 2 5 of 2 6
S u bjects will als o recei ve tra vel rei m b urse me nt of $ 1 0 f or eac h  e val uati o n visit. 
 
P a y me nt C ar d Pr o gr a m
We are partici pati n g i n t he pil ot p hase  of t he Pa y me nt Car d Pr o gra m directe d b y t he Gl o bal Treas ur y 
O perati o ns at C ol u m bia U ni versit y. S u bjects will be c o m pe nsate d t hr o u g h a de bit car d pr o vi de d f or t he m b y 
o ur researc h tea m. T he de bit car ds are iss ue d b y Ba n k of A merica ( B O A).
 
I n or der t o re gister s u bjects t o t heir de bit car ds, s u bject's na me, a d dress, a n d p h o ne n u m ber will be pr o vi de d 
t o B O A.  S u bjects will recei ve o ne rel oa da ble car d a n d t he car d will be “rel oa de d” wit hi n 2 wee ks after eac h 
c o m plete d st u d y visit. T his car d ca n be use d as a cre dit car d O R as a n A T M car d. S u bjects w o ul d als o be 
a ble wit h dra w m o ne y fr o m a ba n k eit her t hr o u g h a ba n k teller or a n A T M mac hi ne.  
R ef er e n c e s
Refere nces
1. Gazzale y, A., et  al., T o p- d o w n s u p pressi o n deficit u n derlies w or ki n g me m or y i m pair me nt i n n or mal 
a gi n g. Nat Ne ur osci, 2 0 0 5. 8( 1 0): p. 1 2 9 8- 3 0 0.
2. S mall, S. A., et al., Selecti ve decli ne i n me m or y f u ncti o n a m o n g healt h y el derl y. Ne ur ol o g y, 1 9 9 9. 5 2( 7): 
p. 1 3 9 2- 6.
3. M orris o n, J. H. a n d M. G. Ba xter, T he a gei n g c ortical s y na pse: hall mar ks a n d i m plicati o ns f or c o g niti ve 
decli ne. Nat Re v Ne ur osci, 2 0 1 2. 1 3( 4): p. 2 4 0- 5 0.
4. S mall, S. A., et al., A pat h o p h ysi ol o gical fra me w or k of hi p p oca m pal d ysf u ncti o n i n a gei n g a n d disease. 
Nat Re v Ne ur osci, 2 0 1 1. 1 2( 1 0): p. 5 8 5- 6 0 1.
5. S mall, S. A., et al., I ma gi n g hi p p oca m pal f u ncti o n acr oss t he h u ma n life s pa n: is me m or y decli ne n or mal 
or n ot? A n n Ne ur ol, 2 0 0 2. 5 1( 3): p. 2 9 0- 5.
6. Yassa, M. A., et al., A ge-relate d me m or y deficits li n ke d t o circ uit-s pecific disr u pti o ns i n t he hi p p oca m p us. 
Pr oc Natl Aca d Sci U S A, 2 0 1 1. 1 0 8( 2 1): p. 8 8 7 3- 8.
7. S mall, S. A., et al., Fr o m T he C o ver: I ma gi n g c orrelates of brai n f u ncti o n i n m o n ke ys a n d rats is olates a 
hi p p oca m pal s u bre gi o n differe ntiall y v ul nera ble t o a gi n g. Pr oc Natl Aca d Sci U S A, 2 0 0 4. 1 0 1( 1 8): p. 
7 1 8 1- 6.
8. Hara, Y., et al., S y na ptic distri b uti o ns of Gl u A 2 a n d P K Mzeta i n t he m o n ke y de ntate g yr us a n d t heir 
relati o ns hi ps wit h a gi n g a n d me m or y. J Ne ur osci, 2 0 1 2. 3 2( 2 1): p. 7 3 3 6- 4 4.
9. M ore n o, H., et al., I ma gi n g t he a beta-relate d ne ur ot o xicit y of Alz hei mer disease. Arc h Ne ur ol, 2 0 0 7. 
6 4( 1 0): p. 1 4 6 7- 7 7.
1 0. Pa vl o p o ul os, E., et al., M olec ular mec ha nis m f or a ge-relate d me m or y l oss: t he hist o ne- bi n di n g pr otei n 
R b A p 4 8. Sci Tra nsl Me d, 2 0 1 3. 5( 2 0 0): p. 2 0 0ra 1 1 5.
1 1. va n Praa g, H., et al., Pla nt- deri ve d fla va n ol (-)e picatec hi n e n ha nces a n gi o ge nesis a n d rete nti o n of s patial 
me m or y i n mice. J Ne ur osci, 2 0 0 7. 2 7( 2 2): p. 5 8 6 9- 7 8.
1 2. Li n W., Celi k A., Pacz y ns ki R. P. Re gi o nal cere bral bl o o d v ol u me: a c o m paris o n of t he d y na mic 
i ma gi n g a n d t he stea d y state met h o ds. J Ma g n Res o n I ma gi n g, 1 9 9 9. 9( 1): p. 4 4 – 5 2.
1 3. W u E, Bric k ma n A, L uc hsi n ger J, et al. T he brai n i n t he a ge of ol d: t he hi p p oca m pal f or mati o n is 
differe ntiall y affecte d b y diseases of late-life. A n n Ne ur ol, 2 0 0 8. 6 4( 4): p. 6 9 8 – 7 0 6

Pr ot oc ol S u m m ar y F or m
7 0 3 4
Sl oa n, Ric har d
P a g e 2 6 of 2 6
1 4. H or n, P., et al. Dietar y fla va n ol i nter ve nti o n l o wers t he le vels of e n d ot helial micr o particles i n c or o nar y 
arter y disease  patie nts. T he Britis h j o ur nal of n utriti o n, 2 0 1 3. 1 1 1( 7): p. 1 2 4 5- 1 2 5 2
1 5. Balzer J, Rassaf T,  Heiss C, Klei n b o n gar d P, La uer T, Mer x M, et al. S ustai ne d be nefits i n vasc ular 
f u ncti o n t hr o u g h fla va n ol-c o ntai ni n g c oc oa i n me dicate d dia betic patie nts a d o u ble- mas ke d, ra n d o mize d, 
c o ntr olle d trial. J A m C oll Car di ol, 2 0 0 8. 5 1( 2 2): p. 2 1 4 1- 9.
1 6. Ka n da, T., et al., Hi g h Si g nal I nte nsit y i n De ntate N ucle us o n U ne n ha nce d T 1- wei g hte d M R I ma ges: 
Ass ociati o n  wit h Li near vers us Macr oc yclic Ga d oli ni u m C helate A d mi nistrati o n. Ra di ol o g y, 2 0 1 5. 2 7 5( 3): 
p. 8 0 3- 9.
1 7. Ra d br uc h, A., et al., Ga d oli ni u m Rete nti o n i n t he De ntate N ucle us a n d Gl o b us Palli d us Is De pe n de nt o n 
t he Class of C o ntrast A ge nt. Ra di ol o g y, 2 0 1 5. 2 7 5( 3): p. 7 8 3- 7 9 1.
 
U pl o a d s
U pl oa d t he e ntire gra nt a p plicati o n(s)
U pl oa d c o p y(ies) of u n b ol de d  C o nse nt F or m(s)
U pl oa d c o p y(ies) of b ol de d C o nse nt F or m(s)
U pl oa d c o p y(ies) of t he HI P A A f or m
HI P A A F or m A. p df
HI P A A N Y S PI F or m. p df
U pl oa d a n y a d diti o nal d oc u me nts t hat ma y be relate d t o t his st u d y

HI P A A F or m A 
HI P A A Cli nic al Rese arc h A ut h oriz ati o n f or S p o ns ore d Rese arc h 
P r ot oc ol N u m ber: 7 0 3 4 
N a me of St u d y: Diet ar y C oc o a Fl a v a n ols a n d A ge- Rel ate d Me m or y Decli ne 
P ri nci p al I n vesti g at or: Dr. Ric h ar d P. Sl o a n 
 
 
F or t he p ur p ose of t he c o n d uct of t he a b o ve n a me st u d y, I a gree t o per mit C ol u m bi a U ni versit y 
Me dic al Ce nter, m y d oct ors a n d m y ot her he alt h c are pr o vi ders (t o get her “ pr o vi ders ”), a n d Dr. 
Ric h ar d P. Sl o a n a n d his/ her st aff (t o get her “ Rese arc hers ”), t o use a n d discl ose he alt h i nf or m ati o n 
a b o ut me as descri be d bel o w. 
 
1.  T he he alt h i nf or m ati o n t h at m a y be use d a n d discl ose d i ncl u des: 
          .  all i nf or mati o n c ollecte d d uri n g t he researc h descri be d i n t he I nf or me d C o nse nt 
             F or m f or t he a b o ve- na me d st u d y (“t he researc h”); a n d 
          .  healt h i nf or mati o n i n m y me dical rec or ds t hat is rele va nt t o t he Researc h. 
          .  T his ma y i ncl u de me dical hist or y i nf or mati o n t hat ma y be c o nsi dere d se nsiti ve,  
              i ncl u di n g:  
 
2.  T he pr o vi ders m a y discl ose he alt h i nf or m ati o n i n m y me dic al rec or ds t o:  
   .  t he Researc hers; 
   .  t he s p o ns or of t he Researc h, Mars I nc.,  a n d its a ge nts a n d c o ntract ors (t o get her “ S p o ns ors”) a n d; 
   .  re prese ntati ves of g o ver n me nt a ge ncies, re vie w b oar ds, a n d ot her pers o ns w h o watc h o ver t he n   
      safet y, effecti ve ness, a n d c o n d uct of t he researc h. 
 
3.  T he rese arc hers m a y use a n d s h are m y he alt h i nf or m ati o n: 
    .  a m o n g t he msel ves a n d wit h ot her partici pati n g researc hers t o c o n d uct t he Researc h; 
    .  re prese ntati ves of g o ver n me nt a ge ncies, re vie w b oar ds, a n d ot her pers o ns w h o watc h o ver t he   
       safet y, effecti ve ness, a n d c o n d uct of researc h; a n d  
    .  as per mitte d b y t he I nf or me d C o nse nt F or m. 
 
4.  T he S p o ns or m a y use a n d s h are m y he alt h i nf or m ati o n as per mitte d b y t he I nf or me d C o nse nt 
F or m. 
 
5.  O nce m y he alt h i nf or m ati o n h as bee n discl ose d t o a t hir d p art y (e. g., a p h ar m ace utic al    
c o m p a n y p artici p ati n g i n t his St u d y), fe der al pri v ac y l a ws m a y n o l o n ger pr otect it fr o m 
f urt her discl os ure.  
 
6.  Ple ase n ote t h at: 
          .  Y o u d o n ot ha ve t o si g n t his A ut h orizati o n, b ut if y o u d o n ot, y o u ma y n ot partici pate i n t he   
             Researc h. 
          .  Y o u ma y c ha n ge y o ur mi n d a n d re v o ke (ta ke bac k) t his a ut h orizati o n at a n y ti me a n d f or a n y   
   
reas o n.  T o re v o ke t his A ut h orizati o n, y o u m ust write t o:  

 
Dr. Ric har d P. Sl oa n 
Be ha vi oral Me dici ne Pr o gra m,  
De pt. of Ps yc hiatr y C ol u m bia U ni versit y Me dical Ce nter  
6 2 2 West 1 6 8 t h Street, S uite 1 5 4 0 
 
 
    .  H o we ver, if y o u re v o ke t his A ut h orizati o n y o u will n ot be all o we d t o c o nti n ue part i n t he 
Researc h. Als o, e ve n if y o u re v o ke t his A ut h orizati o n, t he Researc hers a n d t he S p o ns or ma y 
c o nti n ue t o use a n d discl ose t he i nf or mati o n t he y ha ve alrea d y c ollecte d as per mitte d b y t he 
I nf or me d C o nse nt F or m 
          .  W hile t he Researc h is i n pr o gress, y o u ma y n ot be all o we d t o see y o ur healt h i nf or mati o n t hat is   
              create d or c ollecte d b y C ol u m bia U ni versit y i n t he c o urse of t he Researc h.  After t he Researc h is   
              fi nis he d, h o we ver, y o u ma y be all o we d t o see t his i nf or mati o n. 
 
7.  T his A ut h oriz ati o n d oes n ot h a ve a n e x pir ati o n (e n di n g) d ate. 
 
8.  Y o u will be gi ve n a c o p y of t his A ut h oriz ati o n after y o u h a ve si g ne d it. 
 
 
Pri nte d Na me of S u bj ect: _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Si g nat ure of S u bject or Le gal Re prese ntati ve: _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  Date: _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Relati o ns hi p of Le gal Re prese ntati ve t o S u bject (if a p plica ble): _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
 

F or m  #P P 2:  HI P A A Aut h oriz ati o n  for R es e arc h  4 .1 4 . 14  
N e w Y or k St at e Ps yc hi atric I nstit ut e ( N Y S PI)  
A ut h oriz ati o n t o Us e or Discl os e H e alt h I nf or m ati o n  d uri n g a R es e arc h St u d y  
Pr ot oc ol N u m b er:  
Pri nci p al I n v esti g at or:  
N a m e of St u d y:  
B ef or e r e s e arc h ers c a n us e or s h ar e a n y i d e ntifi a bl e h e alt h i nf or m ati o n  (“H e alt h I nf or m ati o n ”) a b o ut y o u  as p art of t h e 
a b o v e st u d y ( t he “ R es e arc h”), t h e N e w Y or k St at e Ps yc hi atric I nstit ut e ( N Y S PI) is r e q uir e d t o o bt ai n y o ur a ut h oriz ati o n. Y o u a gr e e  
t o all o w t h e f oll o wi n g i n di vi d u als a n d e ntiti es t o us e a n d discl os e H e alt h Inf or m ati o n  a b o ut y o u  a s d escri b e d b el o w: 
•
N e w Y or k St at e  Psyc hi atric I nstit ut e ( N Y S PI), yo ur d oct ors a n d ot h er h e alt h c ar e pr o vi d ers,  if a n y, a n d
•
T h e Pri nci p a l I n v esti g at or a n d his/ h er st aff (t o g et h er “ R es e arc h ers”).   R es e arc h ers m a y i ncl u d e st aff of N Y S PI, t h e N e w Y or k
St at e Offic e of M e nt al H e alt h ( O M H), R es e arc h F o u n d ati o n f or M e nt al H y gi e n e, I nc. ( R F M H), a n d  C ol u m bi a U ni v ersit y ( C U) ,
pr o vi d e d s uc h st aff is a p art of  t h e st u d y, a n d
•
Pr o vi d ers of s er vic es f or t h e R es e arc h at C U,  N Y S PI a n d/ or R F M H,  s uc h as M RI or P E T,  or  C e ntr al  Ref er e nc e  La b or at ori es 
( NK I), if in dic at e d i n t h e  co ns e nt  for m .
1. 
T h e H e alt h  Inf or m ati o n t h at m a y b e us e d a n d / or discl os e d f or t his R es e arc h i ncl u d es:
A ll i nf or m ati o n c oll ect e d d uri n g t h e R es e arc h as t ol d t o y o u i n t h e I nf or m e d C o ns e nt F or m .   
H e alt h  Inf or m ati o n i n y o ur  cli nic al r es e arc h r ec or d w hic h i ncl u d es t h e r es ults of p h ysic al ex a ms, m e dic al a n d 
psyc hi atric hist o r y, l a b or at or y or di a g n ostic t ests, or H e alt h Inf or m ati o n r el ati n g t o a p artic ul ar c o n diti o n t h at is r el at e d  t o 
t h e R es e arc h. 
A d diti o n al i nf or m ati o n m a y i ncl u d e:  
2.
T h e H e alt h  Inf or m ati o n list e d a b o v e m a y b e  discl os e d t o:
R es e arc h ers  a n d t h eir st aff at t h e f oll o wi n g or g a niz ati o ns i n v ol v e d wit h this R es e arc h : 
T h e S p o n s or of t h e R es e arc h, 
a n d its a g e nts a n d c o ntr act ors (t o g et h er,  “ S p o ns or”); a n d  
R e pr es e nt ati v es of r e g ul at or y a n d g o v er n m e nt  a g e nci es, i nstit uti o n al r evi e w b o ar ds, r e pr es e nt ati v es of t h e R es e arc h ers 
a n d t h eir i nstit uti o ns t o t h e l ev el n e e d e d t o c arr y o ut t h eir r es p o nsi biliti es r el at e d t o t h e c o n d uct of t h e r es e arc h.   
Pri v at e l a b or at ori es a n d ot h er p ers o ns a n d or g a niz ati o ns t h at a n al yz e y o ur h e alt h i nf or m ati o n i n c o n n ecti o n wit h 
t his st u d y 
Ot h er (f a mil y m e m b ers or si g nific a nt ot h ers, st u d y b u d di es,  o utsi d e a g e nci es  etc.)  S p ecif y:  
3.
By gi vi n g p er missi o n t o r el e as e y o ur  He alt h Inf or m ati o n as d escri b e d  a b o v e, y o u  u n d ers t a n d t h at y o ur  He alt h
Inf or m ati o n m a y b e disc l os e d t o i n di vi d u als or e ntiti es w hic h  ar e n ot r e q uir e d t o c o m pl y wit h t h e f e d er al a n d st at e pri v ac y l a ws
w hic h g o v er n t h e us e a n d discl os ur e of p ers o n al H e alt h I nf or m ati o n  b y  N Y S PI.    T his m e a ns t h at o n c e y o ur  H e alt h
7 0 3 4
Dr. Ri c h ar d P. Sl o a n, P h. D.
Di et ar y C o c o a Fl a v a n ol s a n d A g e- R el at e d M e m or y D e cli n e
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C ol u m bi a U ni v er sit y M e di c al C e nt er
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Columbia University Medical Center
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Dietary Cocoa Flavanols and Age-Related Memory Decline
Dr. Richard P. Sloan, Ph.D.
7034

F or m  #P P 2:  HI P A A Aut h oriz ati o n  for R es e arc h  4 .1 . 14  
I nf or m ati o n h as b e e n discl os e d t o a t hir d p art y w hic h d o es n ot h a v e t o  f oll o w t h es e l a ws ( e. g., a dr u g c o m p a n y or t h e S p o ns or 
of t h e R es e arc h), it m a y n o l o n g er b e pr ot ect e d  u n d er t h e HI P A A or  N Y S M e nt al H y gi e n e L a w r e q uir e m e nts b ut is s u bj ect t o t h e 
t er ms of t h e c o ns e nt f or m a n d m a y b e s u bj ect t o ot h er st at e or f e d er al pri v ac y l a ws or r e g ul ati o ns.  
4.
Pl e as e n ot e t h at:
•
Y o u d o n ot h a v e t o si g n t his A ut h oriz ati o n  f or m, b ut if y o u d o n ot, y o u m a y n ot b e a bl e t o p artici p at e i n t h e st u d y or
r ec ei v e st u d y r el at e d c ar e.  Y o u m a y c h a n g e y o ur mi n d at a n y ti m e a n d f or a n y r e as o n. If y o u d o s o, y o u  m a y  n o
l o n g er b e allo w e d t o p artici p at e i n t h e st u d y.  If y o u wit h dr a w  t his A ut h oriz ati o n t h e  r es e arc h st aff a n d t h e S p o ns or, if t his
is s p o ns or e d r es e arc h, m a y still us e or discl os e H e alt h  Inf or m ati o n  c o nt ai ni n g i d e ntifyi n g i nf or m ati o n t h ey alr e a d y h a v e
c oll ect e d a b o ut y o u  as n e e d e d  t o m ai nt ai n t h e r eli a bilit y of t h e r es e arc h.  A n y  r e q u est t o wit h dr a w t his  A ut h oriz ati o n
m ust  b e m a d e i n writi n g  t o ( e nt er n a m e a n d c o nt act i nfor m ati o n  b el o w):
•
W hil e t h e R es e arc h is g oi n g o n , y o u m a y n ot b e all o w e d t o r evi e w t h e H e alt h Inf or m ati o n i n y o ur cli nic al r es e arc h
r ec or d t h at h as b e e n cr e at e d or c oll ect e d b y N Y S PI .   W h e n t his r es e arc h h as b e e n c o m pl et e d y o u m a y b e all o w e d t o  s e e
t his i nf or m ati o n.  If it is n e e d e d  f or y o ur c ar e, y o ur H e alt h Inf or m ati o n will b e gi v e n  t o y o u or y o ur D oct or .
5.
T his  A ut h oriz ati o n d o es n ot h a v e a n e n d d at e.
6.
Y o u w ill b e gi v e n a c o p y of t his f or m aft er y o u h a v e si g n e d it.
I a gre e t o t h e us e a n d disc l osur e of H e alt h I nf or m ati o n a b o ut m e as d escri b e d a b o v e:  
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Si g n at ur e of P ar tici p a nt/ L e g al R e pr es e nt ati v e     
D at e  
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Pri nt e d N a m e of P ar tici p a nt 
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R el ati o ns hi p of L e g al R e pr es e nt ati v e t o P artici p a nt (if a p plic a bl e)  
W e als o as k y o u or y o ur l e g al r e pr es e nt ati v e t o i niti al t h e st at e m e nts b el o w:  
I h a ve r ec ei v e d a c o p y of t h e N Y S P I/ O M H N otic e  of Pri v ac y Pr actic es. 
Dr. Ri c h ar d Sl o a n, P h. D. 6 2 2 W e st 1 6 8t h Str e et, P H S uit e 1 5 4 0, N e w Y or k, N Y 1 0 0 3 2
T el: 6 4 6- 7 7 4- 8 9 4 0 E m ail: r p s 7 @ c u m c. c ol u m bi a. e d u
Dr. Richard Sloan, Ph.D. 622 West 168th Street, PH Suite 1540, New York, NY 10032
Tel: 646-774-8940 Email: rps7@cumc.columbia.edu