Angela L Jefferson1, Alexa S Beiser2, Sudha Seshadri3, Philip A Wolf3, Rhoda Au3. 1. Vanderbilt Memory & Alzheimer's Center, Department of Neurology, Vanderbilt University Medical Center, 2525 West End Avenue, Suite 1200, Nashville, TN 37203, USA. 2. Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA National Heart, Lung and Blood Institute's Framingham Heart Study, Framingham, MA, USA Department of Neurology, Boston University School of Medicine, Boston, MA, USA. 3. National Heart, Lung and Blood Institute's Framingham Heart Study, Framingham, MA, USA Department of Neurology, Boston University School of Medicine, Boston, MA, USA.
Abstract
BACKGROUND: The risk apolipoprotein E-4 (APOE4) poses for mild cognitive impairment (MCI) may vary based on the neuropsychological definition of MCI. SETTING: A community-based cohort study. METHODS: Using two psychometric neuropsychological impairment definitions, we examined APOE4 and prevalent MCI among older adults or pre-MCI among middle-aged adults. Neuropsychological, clinical and genetic data were collected on 2,239 Framingham Offspring Cohort participants free from clinical stroke or dementia (62±9 years; 54% women). Prevalent amnestic MCI was defined from neuropsychological performances≥1.5 SD below the mean based on (i) age and education or (ii) age and Wide Range Achievement Test-3 Reading (WRAT-3 Reading) performance adjustment. RESULTS: In the entire sample, multivariable-adjusted logistic regressions found that APOE4 was associated with amnestic MCI when using the age and WRAT Reading definition (odds ratio [OR]=1.7, P=0.002) but not the age and education definition (OR=1.0, P=0.90). Results were modified by age, such that APOE4 was associated with amnestic MCI in participants≥65 years using both the age and WRAT Reading definition (OR=2.4, P<0.001) and the age and education definition (OR=1.7, P=0.04). CONCLUSION: APOE4 risk for prevalent amnestic MCI varies depending on the definition of objective neuropsychological impairment for MCI. Our findings support existing literature emphasising the need to refine MCI neuropsychological profiling methods.
BACKGROUND: The risk apolipoprotein E-4 (APOE4) poses for mild cognitive impairment (MCI) may vary based on the neuropsychological definition of MCI. SETTING: A community-based cohort study. METHODS: Using two psychometric neuropsychological impairment definitions, we examined APOE4 and prevalent MCI among older adults or pre-MCI among middle-aged adults. Neuropsychological, clinical and genetic data were collected on 2,239 Framingham Offspring Cohort participants free from clinical stroke or dementia (62±9 years; 54% women). Prevalent amnestic MCI was defined from neuropsychological performances≥1.5 SD below the mean based on (i) age and education or (ii) age and Wide Range Achievement Test-3 Reading (WRAT-3 Reading) performance adjustment. RESULTS: In the entire sample, multivariable-adjusted logistic regressions found that APOE4 was associated with amnestic MCI when using the age and WRAT Reading definition (odds ratio [OR]=1.7, P=0.002) but not the age and education definition (OR=1.0, P=0.90). Results were modified by age, such that APOE4 was associated with amnestic MCI in participants≥65 years using both the age and WRAT Reading definition (OR=2.4, P<0.001) and the age and education definition (OR=1.7, P=0.04). CONCLUSION:APOE4 risk for prevalent amnestic MCI varies depending on the definition of objective neuropsychological impairment for MCI. Our findings support existing literature emphasising the need to refine MCI neuropsychological profiling methods.
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