Alzheimer disease genetic risk factor APOE e4 and cognitive abilities in 111,739 UK Biobank participants

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Background: the apolipoprotein (APOE) e4 locus is a genetic risk factor for dementia. Carriers of the e4 allele may be more vulnerable to conditions that are independent risk factors for cognitive decline, such as cardiometabolic diseases.

Objective: we tested whether any association with APOE e4 status on cognitive ability was larger in older ages or in those with cardiometabolic diseases.

Subjects: UK Biobank includes over 500,000 middle- and older aged adults who have undergone detailed medical and cognitive phenotypic assessment. Around 150,000 currently have genetic data. We examined 111,739 participants with complete genetic and cognitive data.

Methods: baseline cognitive data relating to information processing speed, memory and reasoning were used. We tested for interactions with age and with the presence versus absence of type 2 diabetes (T2D), coronary artery disease (CAD) and hypertension.

Results: in several instances, APOE e4 dosage interacted with older age and disease presence to affect cognitive scores. When adjusted for potentially confounding variables, there was no APOE e4 effect on the outcome variables.

Conclusions: future research in large independent cohorts should continue to investigate this important question, which has potential implications for aetiology related to dementia and cognitive impairment.

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