Clinical trial NCT01835717: Study for Cognitive and Genetic Characterization of a 45-65 Years Old Population
Official title: Cross-sectional Study for Cognitive and Genetic Characterization of a 45-65 Years Old Population
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Healthy Individuals
Keywords: Preclinical phase of Alzheimer's disease
Asymptomatic phase of Alzheimer's disease
Cognitive normal
Exogenous factors
Endogenous factors
Episodic memory test
Executive function test
Memory binding test validation into Spanish
Memory binding test validation into Catalan
Lead sponsor: Barcelonabeta Brain Research Center, Pasqual Maragall Foundation
Sponsor class: OTHER
Collaborators: name: Obra Social La Caixa, Spain
First posted: 2013-04-19
Enrollment: 2743
Sex: ALL
Minimum age (years): 45
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Cognitive normal men and woman aged 45-75 years

Brief summary: Before Alzheimer's disease (AD) clinical symptoms appear, there is a long period when changes in the brain occur. In this long asymptomatic period or preclinical phase, studies with populations at risk of developing AD have shown cognitive differences compared to control groups without such risk. There is a need for short, sensitive, easily administered, reproducible, non-expensive and independent of socio-demographic influences tests enabling the detection of pre-symptomatic variations in memory, when the memory decline is still within a normal range.

Study main hypothesis: When evaluated with high-demanding tests of memory and executive function, the cognitive performance of cognitive healthy people aged between 45 and 65 and, extensively, to a group of up to 75 years, will vary significantly depending on clinical, socio-demographic and genetic features

Detailed description: The purpose of Study 45-65 is to assess if:

* Endogenous factors (clinical history, risk factors, genetic factors APOE4, etc...), exogenous (socio-demographic, ambient and lifestyle variables) and cognitive reserve (including bilingualism) influence cognitive performance.
* New and/or updated tests translated and validated in Spanish and Catalan when needed, will provide accurate and sensitive measurements of the variability of cognitive performance in this target population, representative of the preclinical phase of Alzheimer's disease.

An optional visit is offered to study participants that includes: cerebral magnetic resonance, vascular ultrasound and olfactory testing.

Eligibility criteria: Inclusion Criteria:

1. Men and women, aged between 45 and 75 years
2. Spanish and/or Catalan speakers
3. Agreement with the study procedures and tests:

   1. Clinical Interview and questionnaires associated to risk factors
   2. Cognitive tests
   3. Blood sample extraction for DNA analysis
4. Close relative involvement for functional evaluation of the volunteer
5. Signature of informed consent

Exclusion Criteria:

1. Cognitive impairment: MMSE \<26, o MIS \<6, or orientation subtest of the Barcelona Test II \<68, o category fluency (animals) \<12
2. Functional status impairment: CDR \> 0
3. Severe auditory and/or visual impairment
4. Neurodevelopmental and/or psychomotor disorder
5. Significant diseases that could currently interfere with cognition: renal failure on hemodialysis, liver cirrhosis, chronic lung disease with oxygen therapy, solid organ transplantation, fibromyalgia, active cancer in treatment or any other disease the investigator considers could affect the participant cognition
6. Major psychiatric disorders (DSM-IV-TR) or diseases that could affect cognitive abilities: major depression, bipolar disorder, schizophrenia and dementia.
7. Neurological disorders: Parkinson's disease, stroke, epilepsy and treatment with frequent seizures (\> 1/month) in the past year, multiple sclerosis or other serious neurological disease.
8. Brain injury interfering with cognition: history of head trauma with parenchymal lesion or extraaxial macroscopic large vessel ischemic stroke or hemorrhagic stroke, brain surgery, brain tumors and other causes that can generate acquired brain damage (cerebral chemotherapy or radiotherapy)
9. Family history of Alzheimer's disease with autosomal dominant (3 affected in two different generations) and early onset age (\<60 years).

Primary outcomes:
measure: Factors influencing the cognitive performance through demanding tests of episodic memory and executive function
timeFrame: single Visit (up to 3 hours)
measure: Culturally adapted validation in Spanish and Catalan of the MBT and determination of normative data for the population under study.
timeFrame: single visit (up to 3 hours)
Secondary outcomes:
measure: Assessment of the equivalence of the in person and over the phone administration to the close relative of the Clinical Dementia Rating (CDR).
timeFrame: single visit/telephone conversation (up to 10 min)
measure: Genetic features of the population
timeFrame: 8 months after study start
measure: Identification of genetic determinants of neuroimaging phenotypes associated to Alzheimer's disease.
timeFrame: 5 years and 8 months after study start
measure: Assessment of the relationship between olfactory and cognitive performance
timeFrame: 5 years and 8 months after study start
measure: Analysis of the relationship between subclinical atherosclerosis and brain changes, cognitive performance and APOE genotype
timeFrame: 6 years and 8 months after study start
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: BarcelonaBeta Brain Research Center
Study officials:
affiliation: Barcelonabeta Brain Research Center, Pasqual Maragall Foundation
name: José Luis Molinuevo, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ciampa I, Operto G, Falcon C, Minguillon C, Castro de Moura M, Pineyro D, Esteller M, Molinuevo JL, Guigo R, Navarro A, Gispert JD, Vilor-Tejedor N, For The Alfa Study. Genetic Predisposition to Alzheimer's Disease Is Associated with Enlargement of Perivascular Spaces in Centrum Semiovale Region. Genes (Basel). 2021 May 27;12(6):825. doi: 10.3390/genes12060825.
citation: Sala-Vila A, Arenaza-Urquijo EM, Sanchez-Benavides G, Suarez-Calvet M, Mila-Aloma M, Grau-Rivera O, Gonzalez-de-Echavarri JM, Crous-Bou M, Minguillon C, Fauria K, Operto G, Falcon C, Salvado G, Cacciaglia R, Ingala S, Barkhof F, Schroder H, Scarmeas N, Gispert JD, Molinuevo JL; ALFA study. DHA intake relates to better cerebrovascular and neurodegeneration neuroimaging phenotypes in middle-aged adults at increased genetic risk of Alzheimer disease. Am J Clin Nutr. 2021 Jun 1;113(6):1627-1635. doi: 10.1093/ajcn/nqab016.
citation: Grau-Rivera O, Navalpotro-Gomez I, Sanchez-Benavides G, Suarez-Calvet M, Mila-Aloma M, Arenaza-Urquijo EM, Salvado G, Sala-Vila A, Shekari M, Gonzalez-de-Echavarri JM, Minguillon C, Ninerola-Baizan A, Perissinotti A, Simon M, Kollmorgen G, Zetterberg H, Blennow K, Gispert JD, Molinuevo JL; ALFA Study. Association of weight change with cerebrospinal fluid biomarkers and amyloid positron emission tomography in preclinical Alzheimer's disease. Alzheimers Res Ther. 2021 Feb 17;13(1):46. doi: 10.1186/s13195-021-00781-z.
citation: Vilor-Tejedor N, Operto G, Evans TE, Falcon C, Crous-Bou M, Minguillon C, Cacciaglia R, Mila-Aloma M, Grau-Rivera O, Suarez-Calvet M, Garrido-Martin D, Moran S, Esteller M, Adams HH, Molinuevo JL, Guigo R, Gispert JD; ALFA Study. Effect of BDNF Val66Met on hippocampal subfields volumes and compensatory interaction with APOE-epsilon4 in middle-age cognitively unimpaired individuals from the ALFA study. Brain Struct Funct. 2020 Nov;225(8):2331-2345. doi: 10.1007/s00429-020-02125-3. Epub 2020 Aug 17.
citation: Ingala S, Mazzai L, Sudre CH, Salvado G, Brugulat-Serrat A, Wottschel V, Falcon C, Operto G, Tijms B, Gispert JD, Molinuevo JL, Barkhof F; ALFA Study. The relation between APOE genotype and cerebral microbleeds in cognitively unimpaired middle- and old-aged individuals. Neurobiol Aging. 2020 Nov;95:104-114. doi: 10.1016/j.neurobiolaging.2020.06.015. Epub 2020 Jun 29.