J Nutr Sci Vitaminol, 70, 344–351, 2024

Prevention of Age-Related-Increases in the Risks of Incident
Functional Disability and Dementia by Home-Delivered Functional
Dairy Product Consumption in Japanese Older Adults
Yasuaki WADA1, Asuka MATSUZAKI TADA2, Meiko YOKOYAMA3,
Miyuki TANAKA1 and Katsunori KONDO3
1

Innovative Research Institute, Morinaga Milk Industry Co., Ltd.,
5–1–83 Higashihara, Zama, Kanagawa 252–8583, Japan
2
MILEI GmbH, Kemptener Strasse 91, 88299, Leutkirch, Germany
3
Department of Social Preventive Medical Sciences, Center for Preventive Medical Sciences,
Chiba University, Chuo-ku, Chiba 260–8670, Japan(Received January 17, 2024)

Summary Dairy products formulated with bioactives are widely distributed in Japan, but
it remains to be clear whether a regular consumption of these products would help reduce
the risks of incidental functional disability and dementia in older adults. This study aimed
to investigate Japanese subjects aged 65 y (n629) that routinely consumed three functional dairy products, a calcium-enriched milk supplemented with Bifidobacterium longum
BB536, a yogurt supplemented with lactoferrin, B. longum BB536 and heat-killed Lacticaseibacillus paracasei MCC1849, and a drinkable yogurt supplemented with lactoferrin, B.
longum BB536 and heat-killed L. paracasei MCC1849, through a home delivery service.
Intake frequency and intake duration of these functional dairy products were comparedwith the risk scores of incident functional disability and dementia, developed by the Japan
Gerontological Evaluation Study. In the participants aged 75 y, the incident functional
disability risk was significantly maintained or decreased in the participants with the long
intake duration level compared with the short intake duration level (OR, 95% CI: 0.48,
0.25–0.93). In the participants aged 75 y, the dementia risk was significantly maintainedor decreased in the participants with the high intake frequency level compared with the low
intake frequency level (OR, 95% CI: 0.46, 0.22–0.95). A high intake frequency or longterm duration of these functional dairy products may be effective in preventing an aging-related increase in the risks of incident functional disability and dementia in older adults, but
this warrants further investigation using different products containing different bioactives.
Key Words bioactives, calcium, dementia, home-delivered functional dairy products, incident functional disability, milk protein, preserving physical function, motivation of goingout, social participation

A demographic shift to older societies proceeds worldwide (1). Incident functional disability has been prevailing among older adults, and dementia is one of themain causes of incident functional disability (2). Hence,
the risks of incident functional disability as well as
dementia need to be addressed to secure the healthierlongevity. Modifiable factors for reducing these risks
include exercise, smoking and alcohol drinking, social
participation, and diet (3). Many epidemiological studies have demonstrated that dairy consumption has beneficial impacts on the physical and cognitive functionsof community-dwelling older adults. Specifically, according to the Hisayama study, one of the oldest cohort
studies of community-dwelling older adults on a large
scale in Japan, higher dairy intake was associated witha lower risk of functional disability and its progression,and the association was considered to be mediated via
an increase in protein intake (4). The Hisayama study
E-mail: ya-wada@morinagamilk.co.jp

also showed that higher dairy intake reduced the risk ofdementia, especially of the Alzheimer’s disease; calcium
and magnesium that are abundant in milk and dairy
products would partly be responsible for this (5, 6). On
the other hand, some of the dairy products are formulated with the addition of bioactives such as prebiotics,
probiotics, and bioactive proteins, and these kinds ofproducts are occasionally labeled with health claims
under the legal regulation (7). However, it has not been
fully proven to what extents these “functional” dairy
products would be effective in reducing the incident
functional disability risk and the dementia risk in older
adults. Especially, long-term intervention studies canhardly be feasible that follow up the onset of incident
functional disability and dementia.
Home delivery service is one of the popular means of
distribution for milk and dairy products, and the consumers normally take these products in a constantmanner for a long period of time. Hence, it was considered that the follow-up of older people who subscribe344

Functional Dairy Products and Geriatric Healthfunctional dairy products through home delivery service may help understand the efficacy of these products
in reducing the risks of incident functional disability
and dementia. We previously conducted a cross-sectional observation study on older adults consuming atleast one of the three home-delivered functional dairy
products, i.e., a calcium-enriched milk supplemented
with Bifidobacterium longum BB536, a yogurt supplemented with lactoferrin, B. longum BB536 and heatkilled Lacticaseibacillus paracasei MCC1849, and a drinkable yogurt supplemented with lactoferrin, B. longum
BB536 and heat-killed L. paracasei MCC1849 (3). B.
longum BB536 is a well-established probiotic effective in
improving gastrointestinal condition (8). It is also oneof the probiotic strains that produce indole-3-lactic
acid, a tryptophan-derived metabolite potentially contributing to brain health through the gut-brain axis (9);this metabolite has been reported to serve as a ligandsof the aryl hydrocarbon receptor and substantially promoted a nerve growth factor-induced neurite outgrowth in the PC12 line of rat adrenal pheochromocytoma cells (10). Lactoferrin is a milk glycoprotein, andis known to exert immunomodulatory effects and alleviate systemic and respiratory symptoms in healthy
adults (11). The heat-killed L. paracasei MCC1849 isa post-biotic, and is known to exert various immunemodulations such as enhancing responsiveness ofacquired immunity to influenza vaccination in people
aged 85 y, and suppressing common cold symptoms
in heathy adults (12–14). In the previous cross-sectional analysis of ours, it was found that the dementia
risk was reduced in subjects aged 75 y consuming
dairy products including these functional dairy products twice/d or more, compared with those having dairy
products less than once/d and not using any of thesefunctional dairy products (3). Potential of these functional dairy products in reducing the dementia risk wasthus suggested, but further studies including longitudinal analyses were warranted to substantiate this.
We hypothesized that a regular consumption of functional dairy products would be effective in reducing therisks of incident functional disability and dementia inolder population. We aimed to conduct a longitudinal
analysis on older adults that routinely consumed
the above-mentioned three functional dairy products
through a home delivery service, and compare the relationship between the intake frequency/duration and therisks of incident functional disability and dementia.
MATERIALS AND METHODS
Participants and study design. The baseline survey
was conducted in 2019 as described previously (3).
Briefly, a total of 7,000 self-administered questionnaires
were sent to older adults aged 65 y, who lived in Aichi
prefecture, Japan, and subscribed at least one of the following functional dairy products; 1) a calcium-enrichedmilk supplemented with B. longum BB536 (Morinaga
Milk Industry, Tokyo, Japan), 2) a yogurt supplemented
with lactoferrin, B. longum BB536 and heat-killed L.
paracasei MCC1849 (Morinaga Milk Industry), and 3) a

345

Table 1. Nutrition facts of functional dairy products(per serving).
MILK(180 mL)

YOGURT(100 g)

D-YOGURT(100 g)Nutrients
Energy113 kcal
93 kcal
62 kcalProtein
8.8 g
3.5 g
3.1 g
Fat
3.8 g
3.6 g
1.0 g
Carbohydrate
10.9 g11.6 g10.1 gSodium
132 mg0.11 g0.11 gCalcium
413 mg
114 mg
103 mgIron
1.0 mg
Not indicated Not indicatedBioactives
BB536
2.0 billion cfu Not indicated Not indicated
Lactoferrin—
100 mg
100 mg
MCC1849—
Not indicated Not indicated
MILK, the calcium-enriched milk supplemented with
Bifidobacterium longum BB536; YOGURT, the yogurt
supplemented with lactoferrin, B. longum BB536 andheat-killed Lacticaseibacillus paracasei MCC1849; and DYOGURT, the drinkable yogurt supplemented with lactoferrin, B. longum BB536 and heat-killed L. paracasei
MCC1849.

drinkable yogurt supplemented with lactoferrin, B.
longum BB536 and heat-killed L. paracasei MCC1849(Morinaga Milk Industry). The choice of these products
and their delivery frequencies were made by each participant freely. These three products were termed hereafter the MILK, the YOGURT, and the D-YOGURT, respectively, and the nutrition facts are presented in Table 1. A
total of 1,536 subjects responded, and 1,230 respondents were eligible for age and residential areas, andprovided written informed consents. The follow-up survey was conducted in 2022, namely 3 y after the baseline survey. The self-administered questionnaires weresent to 897 subjects, who were included in the baseline
survey and kept subscribing the above functional dairy
products as of the date. While 727 subjects responded,
2 subjects were excluded as they were found to be erroneously included despite the baseline age 65 y, 41
excluded as they answered mismatched sex in the twosurveys, 45 excluded as they answered dependence ofactivity of daily living (ADL) or missed answering ADL
dependence/independence in the baseline survey, and10 excluded as they had insufficient information for calculating body mass index (BMI). The remaining 629
respondents were included in the analysis (Fig. 1). This
longitudinal study was conducted in accordance withthe principles of the Declaration of Helsinki and withthe approval of ethics committees of Japan Conferenceof Clinical Research (protocol No. LB-0001, approvedon August 30, 2019).
Dependent variables. The Japan Gerontological Evaluation Study (JAGES) developed a risk assessment scalepredicting incident functional disability (15), and a risk
score for long-term care eligibility certification withdementia onset (16). Both of these were able to be cal-

346

WADA Y et al.

Fig. 1. Flowchart of selecting participants for longitudinal analysis. In the baseline survey, a total of 7,000
self-administered questionnaires were sent to older
adults aged 65 y, who lived in Aichi prefecture, Japan,
and subscribed at least one of the following functional
dairy products; the MILK, the YOGURT, and the D-YOGURT. A total of 1,536 subjects responded, and 1,230
respondents were eligible for age and residential areas,and provided written informed consents. After 3 y, thefollow-up survey was conducted by sending the selfadministered questionnaires to 897 subjects, who were
included in the baseline survey and kept subscribing
the above functional dairy products as of the date.
Among the 727 subjects responded, 629 respondents
were included in the analysis. MILK, the calciumenriched milk supplemented with Bifidobacterium longum
BB536; YOGURT, the yogurt supplemented with lactoferrin, B. longum BB536 and heat-killed Lacticaseibacillus paracasei MCC1849; and D-YOGURT, the drinkableyogurt supplemented with lactoferrin, B. longum BB536
and heat-killed L. paracasei MCC1849.

culated from the self-administered questionnaire in thepresent study, and they were designated here as the“incident functional disability risk score” and the“dementia risk score,” respectively. It is noted that theincident functional disability risk score is calculated
from sex, age, and the 10 survey items regarding exercise capacity, nutritional status, and going out frequency; the contribution of age to this score is considerably large, as the 3-y score change ranges from 1 to 4
points depending on the baseline age. Hence, in thepresent study, the “age-corrected” incident functional
disability risk score was employed for the follow-up survey, by assigning the baseline age for calculation as
done previously (17).
Each risk score change, from the baseline survey tothe follow-up survey, was obtained, which was dichotomized into two risk levels of “increased (delta score0)” and “maintained or decreased (delta score 0).”
They were used as binary dependent variables, andtermed the incident functional disability risk, and thedementia risk, respectively.
Independent variables. Intake “frequency” and “duration” of home delivery functional dairy products at thebaseline were used as independent variables.
The intake frequency of each functional dairy product was surveyed in the self-administered questionnairewith the following six choices: “almost every day (i.e.,
almost 7 servings/wk),” “4–5 servings/wk,” “2–3 servings/wk,” “1 serving/wk,” “scarcely not,” and “never.”
Missing data of intake frequency were treated as“never.” After these 6 frequency choices were weighed
as the frequency of 6.5, 4.5, 2.5, 1, 0.5, and 0 serving(s)/wk, respectively, serving frequencies of the threefunctional dairy products were summed up for eachparticipant on one hand; the summed intake frequency
was then used as an ordinal independent variable withthe three levels: “high frequency (8 servings/wk),”“medium frequency (6–7 servings/wk),” and “low frequency (5 servings/wk).” On the other hand, theintake frequency of each product for each participant
was also employed as another ordinal variable with thelevels: “high frequency (7 servings/wk),” “low &medium frequency (0.5–6.5 servings/wk),” and “zerofrequency (0 serving/wk).”
The intake duration of each functional dairy productwas surveyed in the self-administered questionnairewith the following four choices: “3 y or more,” “2 y or
more but less than 3 y,” “1 y or more but less than 2 y,”and “less than 1 y.” Missing data of intake duration
were treated as “less than 1 y.” The choice of the longest duration among the three products was assigned
for each participant on one hand; the assigned intake
duration was then used as an ordinal independent variable with the three levels: “long duration (3 y),” “middle duration (2–3 y),” and “short duration (2 y),” asthe number of participants of “1 y or more but lessthan 2 y,” and “less than 1 y” were limited (n56 and49, respectively). On the other hand, the intake duration of each product for each participant was also
employed as another ordinal variable with the three levels: “long duration (3 y),” “middle duration (2–3 y),”and “short duration (2 y).”Covariates. Following variables in the baseline survey were used as covariates. Initially, variables thatwould be potential confounding factors associated withthe risks of incident functional disability and/or dementia were included as in our previous report (3): sex (categorical: male or female), age (continuous), householdcomposition (categorical: living alone or living withothers), education attainment (ordinal: 9 y, 10–12 y,or 13 y), economical status (ordinal: poor, fair, orgood), current employment (categorical: unemployed or
employed), comorbidities of hypertension, stroke or diabetes mellitus (categorical: yes or no), current smoking(categorical: yes or no), current alcohol consumption(categorical: yes or no), mealtime environment (categorical: eating alone or eating with others), monthly
social participation (categorical: once or more, or lessthan once), daily walking time (categorical: 1 h or
more, or less than 1 h), and daily intake frequency ofFunctional Dairy Products and Geriatric Health
Table 2. Characteristics of the total participants inbaseline survey.
Total participants(n629)Age (y)
75 y
75 y
Sex
Male
FemaleHousehold composition Livimg alone
Living with others
Education attainment 9 y
10–12 y13 yEconomical status
Poor
Fair
Good
Comorbidity (Yes)
StrokeHypertension
Cardiovasculardiseases
Diabetes mellitus
Alcohol consumption Yes
No
Smoking
Yes
No
Social participation
1/mo
1/mo
Walking time
1 h/d1 h/dEating status
Eating alone
Eating with others
Milk and dairy product 1/d
consumption2
2/d
3/dOther consumption
Meat (1/d)
Fish (1/d)
Egg (1/d)
Soy (1/d)

Table 3. Distribution of functional dairy product consumption according to intake frequency.1
Low

n (%)
74.36.21
345 (54.8%)284 (45.2%)
205 (32.6%)424 (67.4%)
549 (87.3%)
80 (12.7%)
91 (14.9%)304 (48.3%)
231 (36.7%)
45 (7.2%)
386 (61.4%)
198 (31.5%)
13 (2.1%)
259 (41.2%)
51 (8.1%)
70 (11.1%)
215 (34.2%)
414 (65.8%)
33 (5.2%)
596 (94.8%)
169 (26.9%)
460 (73.1%)
75 (11.9%)554 (88.1%)
153 (24.3%)
476 (75.7%)352 (56.0%)
173 (27.5%)
104 (16.5%)
573 (91.1%)
577 (91.7%)
585 (93.0%)550 (87.4%)

1

MeansSDs.
2
Including three functional dairy products surveyed in
the present study.

meat, fish, egg, or soybean (categorical: once/d or more,or less than once/d). Daily intake frequency of milk anddairy product (including functional dairy productintakes) was also employed as an ordinal covariate withthe three levels: “less than once,” “1–2 times,” or “3times or more.” Finally, the baseline level of each risk
score was set as a continuous covariate for the corresponding dependent variable.
Statistical analyses. All data were analyzed using
JMP software (version 14.0.0; SAS Institute, Cary, NC).
Multiple imputation was made for missing data, except
for the variables described above, by performing multivariate singular value decomposition imputation in thesoftware. The risk scores in the baseline survey and thefollow-up survey were compared by using the Wilcoxon
signed-rank test. The intake frequencies or durations offunctional dairy products, in the baseline and follow-up

347

Total (n629)
Baseline
Follow-up
75 y (n345)
Baseline
Follow-up
75 y (n284)
Baseline
Follow-up

MediumHighn (%)
252 (40.1%) 240 (38.2%) 137 (21.8%)
252 (40.1%) 220 (35.0%) 157 (25.0%)n (%)
157 (45.5%) 142 (41.2%) 46 (13.3%)
165 (47.8%) 126 (36.5%) 54 (15.7%)
n (%)
95 (33.5%) 98 (34.5%) 91 (32.0%)
87 (30.6%) 94 (33.1%) 103 (36.3%)

1
Consumption of three functional dairy products surveyed in the present study were presented according tointake frequency levels. No significant difference wasseen in the distributions between the baseline and follow-up surveys in all the participants as well as both of
the two age groups using the Bowker test (p0.22–
0.57).
Low, low intake frequency (5 servings/wk); Medium,medium intake frequency (6–7 servings/wk); and High,high intake frequency (8 servings/wk).

Table 4. Distribution of functional dairy product consumption according to intake duration.1
Short
Total (n629)
Baseline
105 (16.7%)
Follow-up***95 (15.1%)
75 y (n345)
Baseline
66 (19.1%)
Follow-up***52 (15.1%)
75 y (n284)
Baseline
39 (13.7%)
Follow-up#
43 (15.1%)

Middlen (%)
96 (15.3%)
41 (6.5%)n (%)
65 (18.8%)
24 (7.0%)n (%)
31 (10.9%)
17 (6.0%)Long

428 (68.0%)493 (78.4%)
214 (62.0%)269 (78.0%)
214 (75.3%)
224 (78.9%)

1Consumption of three functional dairy products surveyed in the present study were presented according tointake duration levels. Distributions were compared between the baseline and follow-up surveys using the
Bowker test in all the participants as well as both of thetwo age groups. # p0.05 and *** p0.0001.
Short, short intake duration (2 y); Middle, middle
intake duration (2–3 y); and Long, long intake duration(3 y).

surveys, were compared by using the Bowker test. Multiple logistic regression analyses were performed for the
association between the incident functional disability
risk or the dementia risk as a dependent variable, andboth intake frequency and intake duration of the functional dairy products as two independent variables,
which was adjusted for the above-mentioned covariates.
Significance was demonstrated at p0.05.
RESULTS
Characteristics of participants at baseline
Baseline characteristics of the participants are sum-

WADA Y et al.

348

Table 5. Risk scores of incident functional disability
and dementia.1
Baseline
Incident functional disability risk score
Total (n629)
13.58.7
75 y (n345)
7.04.7
75 y (n284)
21.45.4
Dementia risk score
Total (n629)
3.12.1
75 y (n345)
1.61.3
75 y (n284)
5.01.2

Table 6. Association between intake frequency/duration of functional dairy products and risks of incident
functional disability and dementia.1

Follow-up
Incident functional
disability risk score
14.59.32,***
7.64.82,*
22.76.02,***
3.82.2***
2.51.8***
5.41.6***

1

Data are expressed as meansSDs. Scores of the baseline and follow-up surveys were compared by the Wilcoxon signed-rank test. * p0.01 and *** p0.0001.
2
The age-corrected incident functional disability risk
score was employed as reported previously (17).

marized in Table 2. Briefly, the meanSD age was
74.36.2 y, and participants aged 75 y comprised
45.2% (n284) of the total participants. The numberof males and females were 205 and 424, respectively(32.6% and 67.4%, respectively). More than 50% of thetotal participants consumed milk and dairy products(including the three functional dairy products) once/dor less. Approximately 90% of the total participants
consumed meat, fish, egg, or soy once/d or more.
Intake frequency and intake duration of functional dairy
products
The intake frequencies of the three functional dairy
products were compared between the baseline survey
and the follow-up survey in all the participants, the participants aged 75 y, and the participants aged 75 y(Table 3). No significant differences in intake frequency
were seen between the two surveys in all the participants as well as both of the two age groups (p0.22–
0.57). The intake durations of these functional dairy
products were also compared (Table 4), and the intake
duration was found to change significantly from thebaseline survey to the follow-up survey in all of thethree groups (p0.0001–0.05).
Consumption of the three functional dairy products,
expressed as the percentage of each product to all thethree products in each intake frequency level, is shownin Fig. S1 (Supplemental Online Material). The number
and ratio of participants consuming each functional
dairy product in each intake duration level is shown in
Table S1 (Supplemental Online Material).
Incident functional disability risk score and dementia riskscore
The incident functional disability risk score and thedementia risk score were calculated from the selfadministered questionnaire, and the meansSD arepresent for all the participants, the participants aged
75 y, and the participants aged 75 y (Table 5). Bothincident functional disability risk score and dementia
risk score increased significantly from the baseline survey to the follow-up survey in all the participants aswell as both of the age groups (p0.0001–0.01).

Dementia
risk score

Intake frequency
OR (95% CI)
Total
Ref.
Ref.
Low (n252)
Medium (n240) 0.96 (0.66–1.42) 0.83 (0.56–1.23)
1.25 (0.78–2.02) 0.72 (0.44–1.18)
High (n137)
75 y
Ref.
Ref.
Low (n157)
Medium (n142) 1.38 (0.82–2.31) 0.81 (0.45–1.46)
1.48 (0.69–3.18) 1.13 (0.47–2.71)
High (n46)
75 y
Ref.
Ref.
Low (n95)
Medium (n98) 0.52 (0.27–0.98) 0.69 (0.35–1.36)
0.82 (0.41–1.65) 0.46 (0.22–0.95)
High (n91)
Intake duration
Total
Short (n105)
Middle (n96)
Long (n428)
75 y
Short (n66)
Middle (n65)
Long (n214)
75 y
Short (n39)
Middle (n31)
Long (n214)

OR (95% CI)
Ref.
Ref.
1.02 (0.56–1.85) 0.90 (0.48–1.67)
0.72 (0.45–1.17) 0.88 (0.54–1.45)
Ref.
Ref.
0.76 (0.35–1.66) 1.19 (0.47–2.96)
0.48 (0.25–0.93) 0.95 (0.44–2.04)
Ref.
Ref.
1.68 (0.59–4.78) 0.76 (0.25–2.33)
1.29 (0.59–2.84) 0.88 (0.39–2.01)

1

The risks of incident functional disability and dementia
were compared with consumption of three functional
dairy products surveyed in the present study. Multiple
logistic regression analyses were performed for intake frequency and duration (independent variables) and eachscore change from the baseline survey to follow-up survey (dependent variable; dichotomized into two levels of“increased (delta score 0)” and “maintained or decreased (delta score 0)”), adjusting for sex, age, household composition, education attainment, economical status, hypertension, stroke, and diabetes mellitus, smoking,alcohol consumption, mealtime environment, social participation, walking time, intake frequency of meat, fish,
egg, soybean, and milk/dairy products, and baseline levelof each risk score. p0.05 (shown in bold).
Low, low intake frequency (5 servings/wk); Medium,medium intake frequency (6–7 servings/wk); High, highintake frequency (8 servings/wk); Short, short intake
duration (2 y); Middle, middle intake duration (2–3 y);and Long, long intake duration (3 y).

Incident functional disability risk and dementia risk in negative association with intake frequency and intake duration offunctional dairy products
The risks of incident functional disability and dementia were compared with intake frequency of the threefunctional dairy products in all the participants, theparticipants aged 75 y, and the participants aged
75 y (Table 6). The incident functional disability risk

Functional Dairy Products and Geriatric Healthwas significantly maintained or decreased in the participants aged 75 y with the medium intake frequency
level compared with the low intake frequency level (OR,
95% CI: 0.52, 0.27–0.98). The dementia risk was significantly maintained or decreased in the participants
aged 75 y with the high intake frequency level compared with the low intake frequency level (OR, 95% CI:
0.46, 0.22–0.95). These risks were also compared withintake frequency each of these products (Table S2,
Supplemental Online Material). It was found that thedementia risk was significantly maintained or decreased
in all the participants with the high MILK intake frequency level compared with the zero MILK intake frequency level (OR, 95% CI: 0.29, 0.11–0.81), in the participants aged 75 y with the medium and high MILK
intake frequency levels compared with the zero MILK
intake frequency level (OR, 95% CI: 0.08, 0.01–0.76,
and 0.01, 0.01–0.78, respectively), and in the participants aged 75 y with the high MILK intake frequency
level compared with the zero MILK intake frequency
level (OR, 95% CI: 0.19, 0.05–0.76).
The risks of incident functional disability and dementia were also compared with intake duration of thethree functional dairy products (Table 6). The incident
functional disability risk was significantly maintainedor decreased in the participants aged 75 y with thelong intake duration level compared with the shortintake duration level (OR, 95% CI: 0.48, 0.25–0.93).
These risks were also compared with intake durationeach of these products (Table S2). It was found that theincident functional disability risk was significantly
maintained or decreased in the participants aged 75 ywith the middle and long MILK intake duration levelcompared with the short MILK intake duration level(OR, 95% CI: 0.14, 0.02–0.83, and 0.02, 0.02–0.68,
respectively). It was also observed that the dementia risk
was increased in the participants aged 75 y with thelong MILK intake duration level compared with theshort MILK intake duration level (OR, 95% CI: 11.0,
1.1–105.9).
DISCUSSION
This longitudinal study surveyed older adults aged
65 y who kept subscribing the three functional dairy
products for 3 y. Prevention of age-related increases inthese risks were observed in an intake frequency-dependent or an intake duration-dependent manner; anage-related increase in the incident functional disability
risk was prevented in subjects aged 75 y with the long
intake duration level compared with the short intake
duration level; and an age-related increase in thedementia risk was significantly prevented in subjects
aged 75 y with the high intake frequency level compared with the low intake frequency level.
The study participants consisted of more female(67.4%), and about the half the participants were
75 y at the baseline (45.2%) (Table 2). Despite thefact that this study selected subjects subscribing at least
one of the above three functional dairy product througha home delivery service, more than half of the partici-

349

pants answered that they consumed only one serving/dor less of milk and dairy products, indicating that thesefunctional dairy products comprised the large part of
total milk and dairy product consumptions in these participants. During the 3-y survey period, the participants
did not change the type and amount of the functional
dairy product consumption significantly, and kept consuming them for a significant period of time (Tables 3
and 4).
The incident functional disability risk was significantly maintained or decreased in the participants aged
75 y with the long intake duration level comparedwith the short intake duration level of these three functional dairy products, after being adjusted for theabove-mentioned confounding factors (Table 6), which
was compatible with the observation that a maintenance or increase in this risk was also observed in theparticipants aged 75 y with the long MILK intake
duration levels compared with the short MILK intake
duration level (Table S2). More than half of the participants with the long intake duration level consumed the
MILK in the baseline survey, and nearly half of the participants kept consuming the MILK in the follow-up survey (Table S1). When scrutinizing the answers to thequestionnaire items for the age-corrected incident functional disability score, physical function would be preserved in the long intake duration level compared withthe short intake duration level, as suggested by theratios of participants who had increases in the incident
functional disability risk score due to answering “No” to“Do you normally climb stairs without using handrail
or wall for support?” and “No” to “Do you normallywalk continuously for 15 min?” (data not shown). Collectively, the long-term intake of the MILK would contribute to sustaining physical function, leading to prevention of an age-related increase in the incident functional disability risk in subjects aged 75 y. Furthermore, the MILK was rich in milk protein and calcium(Table 1), and these enriched nutrients may be responsible for prevention of an age-related increase in theincident functional disability risk, as has been shownfor milk and dairy products (4). Besides, this association
was significant only in the participants aged 75 y, andcan be interpreted as being that long-term continuous
consumption of the MILK at the early stage of aging
may repel aging-related declines in energy intake andbody weight (18), thereby maintaining or decreasing
the incident functional disability risk.
The dementia risk was significantly maintained or
decreased in participants aged 75 y with the highintake frequency level compared with those with the
low intake frequency level, after being adjusted for confounding factors including comorbidities, socioeconomic status, and dietary habits (3), which was supportive of the observation that a maintenance or
increase in this risk was also observed not only in theparticipants aged 75 y with the high MILK intake frequency level compared with the zero MILK intake frequency level, but also in all the participants with thehigh MILK intake frequency level compared with the350

WADA Y et al.

zero MILK intake frequency level (Table S2). The MILK
was the most consumed product for participants withall the intake frequency levels (Fig. S1c and f), and thedifference of the intake frequency levels could translate
primarily to the difference in the MILK consumption.
When scrutinizing answers to the questionnaire items
for the dementia risk score, the motivation of going out
and social participation would be sustained in the highintake frequency level compared with the low intake
frequency level, as suggested by the ratios of participants who had increases in the dementia risk score due
to answering “No” to “Can you go out by bus or train by
yourself?” and answering “Never” to “How often do you
participate in the sports groups or clubs?” (data notshown). Collectively, the high intake frequency of the
MILK would lead to the motivation of going out andsocial participation in subjects aged 75 y. Of note, sufficient calcium intake is known to be vascular-protective and associated with the reduction in the risk ofdementia (5), and calcium rich in the MILK could be
responsible for prevention of an age-related increase in
the dementia risk. Besides, the MILK was formulatedwith 2 billions cfu/serving of B. longum BB536, which
is one of the probiotics that produces an indole-3-lactic
acid, a metabolite potentially contributing to brain
health (9). However, the association between this probiotic strain and brain health has not been elucidated todate in humans, and effects of probiotics on humanbrain health has normally been confirmed when they
are taken in higher doses (5–20 billion cfu/d) (19–21).
Still, the association between the intake frequency ofthese functional dairy products and the dementia risk
might reflect the fact that higher doses are importantfor probiotic strains to exert a brain health-promoting
effect. Finally, a decrease in the dementia risk was moreevident in the participants aged 75 y in the present
study. This may be related to the fact that the age group
75–79 comprised the largest proportion of total dementia onset in Asian population aged 60 y, which is followed by the age group 80–84 y (22). Namely, subjects
aged 75 y are highly susceptible to dementia, and theeffect of dietary factors on dementia might be easier tobe manifested in this age group.
One of the largest limitations was missing of theappropriate control group, i.e., subjects with no use offunctional dairy products. Instead, this study compared
the subjects with different intake frequency/durationlevels of the three functional dairy products. Preventionof age-related increases in these risks were observed in
an intake frequency-dependent or an intake duration-dependent manner, thus considerably supporting
the usefulness of these functional dairy products in suppressing these risks. Still, additional studies are necessary to substantiate the certainty of this notion by
including the control group. Another large limitation
was that this study examined only three kinds of functional dairy products, and a more variety of commercial
functional dairy products with different bioactives shallbe investigated to gain more insights into the role offunctional dairy products in the health of older adults.

In conclusion, age-related increased risks of incident
functional disability and dementia can be prevented inolder adults by regularly consuming three functional
dairy products surveyed in the present study, as we
hypothesized. Prevention of an age-related increase in
the incident functional disability risk is more likely to be
manifested in subjects aged 75 y, and prevention ofan age-related increase in the dementia risk is more
likely to become evident in subjects aged 75 y. Nutrients such as milk protein and calcium, and a probiotic
might be responsible for these effects, but further investigations are necessary using different functional dairy
products with different bioactives to consolidate theeffectiveness of functional dairy products in geriatrichealth.
Authorship
A.M.T., M.T., and K.K. conceived the study; A.M.T.,
M.Y., and K.K. designed the study; Y.W. and A.M.T. conducted experiments and analyzed the data; Y.W. interpreted the data and wrote the manuscript; and Y.W. had
primary responsibility for the final content. All authors
have read and agreed to the manuscript.
Disclosure of state of COI
Y.W., A.M.T., and M.T. are the employees of Morinaga
Milk Industry Co., Ltd. M.Y. and K.K. declare no conflicts of interest.
Acknowledgments
We appreciate great contributions of the participantsin this survey.
Funding
This study was funded by Morinaga Milk Industry
Co., Ltd.
Supporting Information
Supplemental online material is available on J-STAGE.
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