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Cerebrovascular risk factors and preclinical memory decline in healthy APOE ?4 homozygotes.

ABSTRACT: To characterize the effects of cerebrovascular (CV) risk factors on preclinical memory decline in cognitively normal individuals at 3 levels of genetic risk for Alzheimer disease (AD) based on APOE genotype.We performed longitudinal neuropsychological testing on an APOE ?4 enriched cohort, ages 21-97. The long-term memory (LTM) score of the Auditory Verbal Learning Test (AVLT) was the primary outcome measure. Any of 4 CV risk factors (CVany), including hypercholesterolemia (CHOL), prior cigarette use (CIG), diabetes mellitus (DM), and hypertension (HTN), was treated as a dichotomized variable. We estimated the longitudinal effect of age using statistical models that simultaneously modeled the cross-sectional and longitudinal effects of age on AVLT LTM by APOE genotype, CVany, and the interaction between the two.A total of 74 APOE ?4 homozygotes (HMZ), 239 ?4 heterozygotes (HTZ), and 494 ?4 noncarriers were included. APOE ?4 carrier status showed a significant quadratic effect with age-related LTM decline in all models as previously reported. CVany was associated with further longitudinal AVLT LTM decline in APOE ?4 carriers (p=0.02), but had no effect in noncarriers. When ?4 HTZ and HMZ were considered separately, there was a striking effect in HMZ (p<0.001) but not in HTZ. In exploratory analyses, significant deleterious effects were found for CIG (p=0.001), DM (p=0.03), and HTN (p=0.05) in APOE ?4 carriers only that remained significant only for CIG after correction for multiple comparisons.CV risk factors influence age-related memory decline in APOE ?4 HMZ.

SUBMITTER: Caselli RJ

PROVIDER: S-EPMC3068011 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature

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Cerebrovascular risk factors and preclinical memory decline in healthy APOE ε4 homozygotes.

Caselli R J RJ Dueck A C AC Locke D E C DE Sabbagh M N MN Ahern G L GL Rapcsak S Z SZ Baxter L C LC Yaari R R Woodruff B K BK Hoffman-Snyder C C Rademakers R R Findley S S Reiman E M EM

Neurology 20110216 12

<h4>Objective</h4>To characterize the effects of cerebrovascular (CV) risk factors on preclinical memory decline in cognitively normal individuals at 3 levels of genetic risk for Alzheimer disease (AD) based on APOE genotype.<h4>Methods</h4>We performed longitudinal neuropsychological testing on an APOE ε4 enriched cohort, ages 21-97. The long-term memory (LTM) score of the Auditory Verbal Learning Test (AVLT) was the primary outcome measure. Any of 4 CV risk factors (CVany), including hyperchol ...[more]

PMID: 21325652

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Project description:An unfortunate result of the rapid rise in geriatric populations worldwide is the increasing prevalence of age-related cognitive disorders such as Alzheimer's disease (AD). AD is a devastating neurodegenerative illness that is characterized by a profound impairment of cognitive function, marked physical disability, and an enormous economic burden on the afflicted individual, caregivers, and society in general. The rise in elderly populations is also resulting in an increase in individuals with related (potentially treatable) conditions such as "Mild Cognitive Impairment" (MCI) which is characterized by a less severe (but abnormal) level of cognitive impairment and a high-risk for developing dementia. Even in the absence of a diagnosable disorder of cognition (e.g., AD and MCI), the perception of increased forgetfulness and declining mental function is a clear source of apprehension in the elderly. This is a valid concern given that even a modest impairment of cognitive function is likely to be associated with significant disability in a rapidly evolving, technology-based society. Unfortunately, the currently available therapies designed to improve cognition (i.e., for AD and other forms of dementia) are limited by modest efficacy and adverse side effects, and their effects on cognitive function are not sustained over time. Accordingly, it is incumbent on the scientific community to develop safer and more effective therapies that improve and/or sustain cognitive function in the elderly allowing them to remain mentally active and productive for as long as possible. As diagnostic criteria for memory disorders evolve, the demand for pro-cognitive therapeutic agents is likely to surpass AD and dementia to include MCI and potentially even less severe forms of memory decline. The purpose of this review is to provide an overview of the contemporary therapeutic targets and preclinical pharmacologic approaches (with representative drug examples) designed to enhance memory function.

Dataset Information

Cerebrovascular risk factors and preclinical memory decline in healthy APOE ?4 homozygotes.

Publications

Cerebrovascular risk factors and preclinical memory decline in healthy APOE ε4 homozygotes.

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