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

ABSTRACT: 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 ?4 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.

SUBMITTER: Talboom JS

PROVIDER: S-EPMC6615857 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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

Talboom Joshua S JS Håberg Asta A De Both Matthew D MD Naymik Marcus A MA Schrauwen Isabelle I Lewis Candace R CR Bertinelli Stacy F SF Hammersland Callie C Fritz Mason A MA Myers Amanda J AJ Hay Meredith M Barnes Carol A CA Glisky Elizabeth E Ryan Lee L Huentelman Matthew J MJ

eLife 20190618

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, se ...[more]

PMID: 31210642

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Project description:Alzheimer's disease (AD) is a devastating, progressive neurodegenerative disease resulting in memory loss and a severe reduction in the ability to perform activities of daily living. Ethnicity-related genetic factors promoting the development of dementias among African Americans (AA) and increased risk among women for developing AD indicates that AA women with a parental history of AD are at great risk for developing AD. This phase I study assessed the impact of a 12 week, 20-lesson adapted Argentine Tango intervention (n = 24) to a no-contact control group (n = 10) on measures of plasma inflammatory markers, cognition, and motor and psychosocial performance in middle-aged AA woman at increased risk for AD by virtue of parental history. Some woman (n = 16) were also caregivers; thus, the impact of the intervention on caregiving burden was examined in this subset. Preliminary analysis of efficacy was conducted with significance tests on biomarkers and key measures of cognition, including visuospatial and executive function, balance, and strength. After 12 weeks, Tango participants had significantly decreased inflammatory cytokine, including reductions in IL-7 (p = 0.003), IFN-γ (p = 0.011), TNFα (p = 0.011), and MCP-1 (p = 0.042) compared to controls. Large effects were noted for the Tango group on tests of executive functioning (d = 0.89), and inhibition (p = 0.031). Participants in Tango improved in dynamic and static balance (p = 0.018) and functional lower body strength (p = 0.023). Secondary assessment revealed trends favoring the intervention group were noted in spatial cognition and executive function. Moderate effects were noted in caregiving burden measures among the subset of caregivers. These data demonstrate substantial reductions in inflammatory biomarkers along with cognitive and motor improvements through a non-pharmacologic, affordable intervention among a small, well-characterized cohort of AA women with a parental history of AD.

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

Publications

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

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