Clinical trial NCT03628404: Defining the Genetic Etiology of Alzheimer's Disease in the Faroe Islands
Official title: Defining the Genetic Etiology of Alzheimer's Disease in the Faroe Islands
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Alzheimer Disease
Dementia
Keywords: Alzheimer disease
Dementia
Faroe Islands
Isolated population
Environmental exposure
Lead sponsor: Faroese Hospital System
Sponsor class: OTHER
First posted: 2018-08-14
Enrollment: 1000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: OTHER
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This is a population based study conducted in the Faroe Islands, a small island population with approximately 50.000 inhabitants. Individuals diagnosed with dementia are being recruited from the only Dementia Clinic on the islands. Family members are also recruited. Control subjects are randomly selected from the Faroese Population Registry, matched by sex and age to the cases. Te

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Sequenom iPLEX genotyping and exome sequencing to identify and characterize genetic contributions to etiology of Alzheimer disease and other dementias
timeFrame: At baseline
Secondary outcomes:
measure: Influence of polychlorinated biphenyl exposure on the risk of AD
timeFrame: At baseline
measure: Influence of perfluorinated alkylated substance exposure on the risk of AD
timeFrame: At baseline
measure: Influence of mercury exposure on the risk of AD
timeFrame: At baseline
measure: MMSE
timeFrame: At baseline
measure: ACE
timeFrame: At baseline
measure: NPI-Q
timeFrame: At baseline
measure: FAQ IADL
timeFrame: At baseline
Other outcomes:
Locations:
city: Tórshavn
country: Faroe Islands
facility: The Faroses Hospital System
Study officials:
References: