Defining the Genetic Etiology of Alzheimer's Disease in the Faroe Islands

Recruiting

• Conditions: Dementia; Alzheimer Disease

• Registration Number: NCT03628404
• Lead Sponsor: Faroese Hospital System

Brief Summary

The investigators established the Faroese Alzheimer's Cohort with the aim to unravel genetic and environmental factors that influence the risk and/or susceptibility of Alzheimers disease (AD). It is believed the Faroese population represents a unique opportunity due to its characteristics as a geographic, environmental and genetic isolate with a homogeneous genetic background and founder effects. It has an 'engaged' population with superbly detailed genealogy going 400 years back, unfettered patient access to health care, traditionally high participation rates in research and low probability of losing subjects to follow-up, and presents a unique opportunity to more readily identify genetic and environmental factors involved in AD.

The specific aims of this project are:

1. Enrolment of patients with AD, incl.1st degree family members of selected familial patients and age and gender matched control subjects.

2. Detailed genealogical investigation of patients with Alzheimer's disease

3. Identify genes influencing risk and/or susceptibility of AD in the Faroese population

Detailed Description

The aim of the study is to unravel genetic and environmental factors that influence the risk and/or susceptibility of AD. Thus, subjects with AD and family members when there is a strong history of AD are being recruited. Data collection includes a blood sample, clinical phenotype data from hospital records, standardized assessment scales (e.g. Geriatric Depression Scale (GDS), Neuropsychiatric Inventory Questionnaire (NPI-Q), Functional Activities Questionnaire (FAQ-IADL), tests of mental function (Mini Mental State Examination (MMSE) and Addenbrooke's Cognitive Examination (ACE)) and family and lifestyle/environmental questionnaire. Furthermore are control subjects being recruited where data includes a blood sample, MMSE and a lifestyle/environmental questionnaire.

Initial genetic analyses will focus on known genetic risk factors for AD by looking at the most highly associated single nucleotide polymorphisms in loci harboring e.g. apolipoprotein E (APOE)/Translocase Of Outer Mitochondrial Membrane 40 (TOMM40), MAPT, Phosphatidylinositol Binding Clathrin Assembly Protein (PICALM). Subsequent analyses will focus on genome-wide array genotyping of \~ 1.8 million markers, e.g. to accommodate the population structure. Finally, patients with a family history of AD who cannot be explained by the before mentioned analysis will be subject to exome sequencing. Exposure analyses will focus on persistant organic pollutants, e.g. polychlorinated biphenyls (PCBs), perfluorinated alkylated substances (PFAS) and also mercury.

The investigators believe the Faroese population presents a unique opportunity to more readily identify genetic and environmental factors involved in AD due to its characteristics as a geographic, environmental and genetic isolate with a homogeneous genetic background.

Study Timeline

• Study Start: 2015-09-01
• Study First Submitted: 2018-08-06
• Study First Submitted QC: 2018-08-09
• Study First Posted: 2018-08-14
• Status Verified: 2022-03
• Last Update Submitted: 2022-03-15
• Last Update Posted: 2022-03-17
• Primary Completion: 2025-01-01
• Study Completion: 2025-01-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1000

Inclusion Criteria

• diagnosis of dementia (cases)
• Age and gender matched to cases (controls)
• Close relatives to an individual with dementia (family members)

Exclusion Criteria

• No exclusion criteria (cases and family members)
• Sign of dementia assessed by MMSE (controls)

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Sequenom iPLEX genotyping and exome sequencing to identify and characterize genetic contributions to etiology of Alzheimer disease and other dementias	At baseline	Genetic cause of disease

Secondary Outcome Measures

Name	Time	Method
Influence of polychlorinated biphenyl exposure on the risk of AD	At baseline	Polychlorinated biphenyls levels measured in serum
MMSE	At baseline	Mini Mental State Examination
FAQ IADL	At baseline	Functional Activities Questionnaire / Functional Assessment Questionnaire
Influence of perfluorinated alkylated substance exposure on the risk of AD	At baseline	Perfluorinated alkylated substances (PFAS) levels measured in serum
ACE	At baseline	Addenbrooke's cognitive examination
Influence of mercury exposure on the risk of AD	At baseline	Mercury levels measured in blood
NPI-Q	At baseline	The Neuropsychiatric Inventory

Trial Locations

Locations (1)

The Faroses Hospital System; 🇫🇴 Tórshavn, Faroe Islands