Background: Cognitive decline is a major threat to the elderly, which can be expected to accelerate as life expectancy increases. Extensive evidence indicates cardiovascular risk factors (CVRFs) are also associated with an increased risk of cognitive decline. This evidence, however, comes from samples predominantly under age 75. Findings from our group and others suggest that relationships between high levels of CVRFs with poor cognitive outcomes may be diminished or reversed in older samples. Thus, such risk factors might be useful as indicators for successful cognitive aging - maintaining intact cognition into old age despite a high risk of cognitive decline. For example, in cross-sectional analyses, our group has found provocative associations of greater levels of the C-reactive protein (CRP) - a marker for inflammation associated with cognitive decline in the younger elderly - with better, not worse, memory in very old (75+ years) subjects, and also with lower risk for dementia in their family members. The e4 allele of the APOE gene is conclusively associated with increased risk for cognitive decline and AD, but this association diminishes with increasing age. This interaction of APOE-e4 and age may also be interpreted as a stronger association of age with cognitive decline for those without the APOE-e4 allele. Similar provocative interactions with age have been observed with several other CVRFs - total cholesterol, hemoglobin A1c, systolic blood pressure, and ejection fraction, a direct measure of heart function. Methods: We will study very old, cognitively intact, community-dwelling, male Veterans recruited from the James J. Peters Veterans Affairs Medical Center. Some of the subjects have already been consented, assessed for CVRFs and cognition at baseline, and followed cognitively at least once. We will continue to follow these subjects cognitively, and supplement them by recruiting additional very old Group 1 scores Veterans. We will focus on five baseline CVRFs as predictors of longitudinal cognitive change. Objectives:
Aim 1 assesses total cholesterol, CRP, hemoglobin A1c, ejection fraction, systolic blood pressure as predictors of the rate of longitudinal cognitive decline. We hypothesize that putatively high risk baseline levels of CVRFs will be associated with a lower rate of decline of memory function.
Aim 2 compares these associations for subjects over age 85 at entry (oldest-old) with those between age 75-84 (moderately-old). We hypothesize that baseline CVRF levels associated with greater cardiovascular risk in the young elderly will be associated with lower rates of decline of memory function in the oldest old than the moderately old.
Aim 3 compares these associations by the presence or absence of the apoliprotein E4 allele. We hypothesize that baseline CVRF levels associated with greater cardiovascular risk in the young elderly will be associated with lower rates of decline of memory function in subjects without an APOE-e4 allele than in those with it. Public Health Implications: Since there are few studies focusing on very old males, this study will have major public health implications for elderly veterans, and the general population. Identifying subgroups with particularly high risk associated with CVRFs has the potential for targeting preventions against or treatments of cognitive decline. The innovation of this study is seeking predictors of cognitive success in very old male veterans who are high risk for impairment, which may lead to identification of protective or preventive factors.
Cognitive decline is a major threat to Veterans, especially as life expectancy increases. Some cardiovascular risk factors (CVRFs) associated with increased risk of cognitive decline in samples under age 75 are diminished or even reversed in older samples. Most risk studies of the very elderly have predominantly female samples;this study of 75+ year old, cognitively intact male veterans is much more relevant to the VA mission. We will assess risk of cognitive decline associated with five CVRFs, and subjects over age 85 with those aged 75-84 years. Identifying CVRFs associated with particularly high risk of cognitive decline has the potential for targeting preventions against or treatments of cognitive decline. The innovation of this study is characterizing subgroups of the very elderly that are cognitively successful despite having CVRFs that suggest high risk for impairment. Identifying specific characteristics of such groups may lead to protective or preventive factors.
|Silverman, Jeremy M; Schmeidler, James (2018) The protected survivor model: Using resistant successful cognitive aging to identify protection in the very old. Med Hypotheses 110:9-14|
|Silverman, Jeremy M; Schmeidler, James (2018) Outcome age-based prediction of successful cognitive aging by total cholesterol. Alzheimers Dement 14:952-960|