Family history of Alzheimer's disease alters cognition and is modified by medical and genetic factors

In humans, a first-degree family history of dementia (FH) is a well-documented risk factor for Alzheimer's disease (AD); however, the influence of FH on cognition across the lifespan is poorly understood. To address this issue, we developed an internet-based paired-associates learning (PAL) tas...

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Bibliographic Details
Published in:	eLife Vol. 8
Main Authors:	Talboom, Joshua S, Håberg, Asta, De Both, Matthew D, Naymik, Marcus A, Schrauwen, Isabelle, Lewis, Candace R, Bertinelli, Stacy F, Hammersland, Callie, Fritz, Mason A, Myers, Amanda J, Hay, Meredith, Barnes, Carol A, Glisky, Elizabeth, Ryan, Lee, Huentelman, Matthew J
Format:	Journal Article
Language:	English
Published:	England eLife Science Publications, Ltd 18-06-2019 eLife Sciences Publications Ltd eLife Sciences Publications, Ltd
Subjects:	Adolescent Adult Advertising executives Age Aged Aged, 80 and over Alleles Alzheimer Disease - genetics Alzheimer Disease - physiopathology Alzheimer's Disease Apolipoprotein E Apolipoprotein E (APOE) Apolipoprotein E4 - genetics Apolipoproteins Cognition Cognition & reasoning Dementia Dementia disorders Diabetes mellitus Education Educational attainment Educational Status Epigenetic inheritance Family family history Family medical history Female Genetic aspects Genetic factors Genotype & phenotype Health aspects Human Biology and Medicine Humans internet-based Learning Life span Male Memory Middle Aged Neuroscience paired-associates learning Risk factors Variables Young Adult United States United States > US human biology Apolipoprotein E (APOE) paired-associates learning Alzheimer's Disease family history neuroscience internet-based dementia medicine human
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Summary:	In humans, a first-degree family history of dementia (FH) is a well-documented risk factor for Alzheimer's disease (AD); however, the influence of FH on cognition across the lifespan is poorly understood. To address this issue, we developed an internet-based paired-associates learning (PAL) task and tested 59,571 participants between the ages of 18-85. FH was associated with lower PAL performance in both sexes under 65 years old. Modifiers of this effect of FH on PAL performance included age, sex, education, and diabetes. The Apolipoprotein E ε4 allele was also associated with lower PAL scores in FH positive individuals. Here we show, FH is associated with reduced PAL performance four decades before the typical onset of AD; additionally, several heritable and non-heritable modifiers of this effect were identified.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2050-084X 2050-084X
DOI:	10.7554/eLife.46179