Study for Cognitive and Genetic Characterization of a 45-65 Years Old Population

NCT01835717 | Completed

• 1 other identifier: Study 45-65/FPM 2012
• Study Type: observational
• Target: 2,743
• Locations: 1 country
• Sites: 1

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

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

Outcome Measures

Primary Outcomes (2)

• Factors influencing the cognitive performance through demanding tests of episodic memory and executive function

  The following tests will be administered: Verbal episodic memory: MBT (Memory Binding Test) WAIS-IV subsets: 1 Perceptual reasoning (Visual Puzzles) 2 Logical reasoning (Matrix Reasoning) 3 Executive attention and working memory (Digit span) 4 Speed of processing (Coding) 5 Abstract verbal reasoning (Similarities) Factors to be considered: Hypertension, diabetes mellitus, and metabolic syndrome APOE4 Cognitive reserve (including bilingualism) Pollution, exposure to toxics, diet

  single Visit (up to 3 hours)

• Culturally adapted validation in Spanish and Catalan of the MBT and determination of normative data for the population under study.

  single visit (up to 3 hours)

Secondary Outcomes (5)

• Assessment of the equivalence of the in person and over the phone administration to the close relative of the Clinical Dementia Rating (CDR).

  single visit/telephone conversation (up to 10 min)

• Genetic features of the population

  8 months after study start

• Identification of genetic determinants of neuroimaging phenotypes associated to Alzheimer's disease.

  5 years and 8 months after study start

• Assessment of the relationship between olfactory and cognitive performance

  5 years and 8 months after study start

• Analysis of the relationship between subclinical atherosclerosis and brain changes, cognitive performance and APOE genotype

  6 years and 8 months after study start

Study Arms (1)

Cognitively normal individuals

Eligibility Criteria

• Age: 45 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Cognitive normal men and woman aged 45-75 years

You may qualify if:

• Men and women, aged between 45 and 75 years
• Spanish and/or Catalan speakers
• Agreement with the study procedures and tests:
• Clinical Interview and questionnaires associated to risk factors
• Cognitive tests
• Blood sample extraction for DNA analysis
• Close relative involvement for functional evaluation of the volunteer
• Signature of informed consent

You may not qualify if:

• Cognitive impairment: MMSE \<26, o MIS \<6, or orientation subtest of the Barcelona Test II \<68, o category fluency (animals) \<12
• Functional status impairment: CDR \> 0
• Severe auditory and/or visual impairment
• Neurodevelopmental and/or psychomotor disorder
• 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
• Major psychiatric disorders (DSM-IV-TR) or diseases that could affect cognitive abilities: major depression, bipolar disorder, schizophrenia and dementia.
• 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.
• 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)
• Family history of Alzheimer's disease with autosomal dominant (3 affected in two different generations) and early onset age (\<60 years).

Sponsors & Collaborators

• Barcelonabeta Brain Research Center, Pasqual Maragall Foundation: lead
• Obra Social La Caixa, Spain: collaborator

Study Sites (1)

BarcelonaBeta Brain Research Center

Barcelona, 08005, Spain

Location

Related Publications (6)

• Cumplido-Mayoral I, Garcia-Prat M, Operto G, Falcon C, Shekari M, Cacciaglia R, Mila-Aloma M, Lorenzini L, Ingala S, Meije Wink A, Mutsaerts HJMM, Minguillon C, Fauria K, Molinuevo JL, Haller S, Chetelat G, Waldman A, Schwarz AJ, Barkhof F, Suridjan I, Kollmorgen G, Bayfield A, Zetterberg H, Blennow K, Suarez-Calvet M, Vilaplana V, Gispert JD; ALFA study; EPAD study; ADNI study; OASIS study. Biological brain age prediction using machine learning on structural neuroimaging data: Multi-cohort validation against biomarkers of Alzheimer's disease and neurodegeneration stratified by sex. Elife. 2023 Apr 17;12:e81067. doi: 10.7554/eLife.81067.

  PMID: 37067031 DERIVED

• 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.

  PMID: 34072165 DERIVED

• 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.

  PMID: 33733657 DERIVED

• 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.

  PMID: 33597012 DERIVED

• 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.

  PMID: 32804326 DERIVED

• 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.

  PMID: 32791423 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

serum; white cells

Study Officials

• José Luis Molinuevo, MD, PhD

  Barcelonabeta Brain Research Center, Pasqual Maragall Foundation

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 15, 2013
• First Posted: April 19, 2013
• Study Start: April 1, 2013
• Primary Completion: August 30, 2019
• Study Completion: December 31, 2020
• Last Updated: June 10, 2021

Record last verified: 2021-06

Locations

ES (1)