Carrington Rice Wendell

Longitudinal examination of obesity and cognitive function: results from the Baltimore longitudinal study of aging.

Background: Obesity indices (i.e. BMI, waist-to-hip ratio) show differential relationships to other health outcomes, though their association to neurocognitive outcome is unclear. Methods: We examined whether central obesity would be more closely associated with cognitive function in 1,703 participants from the Baltimore Longitudinal Study of Aging. Results: Longitudinal mixed-effects regression models showed multiple obesity indices were associated with poorer performance in a variety of cognitive domains, including global screening measures, memory, and verbal fluency tasks. Obesity was associated with better performance on tests of attention and visuospatial ability. An obesity index by age interaction emerged in multiple domains, including memory and attention/executive function. Conclusion: Obesity indices showed similar associations to cognitive function, and further work is needed to clarify the physiological mechanisms that link obesity to poor neurocognitive outcome.

Carotid Intimal Medial Thickness Predicts Cognitive Decline Among Adults Without Clinical Vascular Disease

Background and Purpose— Though clinical cardiovascular and cerebrovascular diseases are established risk factors for cognitive decline and dementia, less is known about the relations between vascular health and cognition among individuals without these diseases. Carotid intimal medial thickness (IMT), a measure of subclinical vascular disease, is associated with concurrent decrements in cognitive function, but relatively little research has examined longitudinal relations between carotid IMT and prospective cognitive decline. Methods— We examined relations of carotid IMT to prospective trajectories of cognitive function among 538 (aged 20 to 93, 39% male, 66% white) participants in the Baltimore Longitudinal Study of Aging (BLSA) free of known cardiovascular, cerebrovascular, and neurological disease. Participants underwent initial carotid ultrasonography and repeat neuropsychological testing on up to 8 occasions over up to 11 years of follow-up. Mixed-effects regression analyses were adjusted for age, gender, race, education, mean arterial pressure, body mass index, total cholesterol, smoking, depressive symptoms, and cardiovascular medication use. Results— Individuals with greater carotid IMT displayed accelerated decline in performance over time on multiple tests of verbal and nonverbal memory, as well as a test of semantic association fluency and executive function. Conclusions— Carotid IMT predicts accelerated cognitive decline, particularly in the domain of memory, among community-dwelling individuals free of vascular and neurological disease.

Psychometric Limitations of the Mini-Mental State Examination Among Nondemented Older Adults: An Evaluation of Neurocognitive and Magnetic Resonance Imaging Correlates

Background/Study Context: Although many of the Mini-Mental State Examinations (MMSE) limitations are well accepted among geriatricians, neuropsychologists, and other interested clinicians and researchers, its continued use in psychometrically unsound ways suggests that additional investigation and dissemination of information are sorely needed. The authors aimed to describe the reliability and validity of the MMSE as a measure of cognitive function among healthy older adults. Methods: The authors examined MMSE performance in 124 stroke- and dementia-free, community-dwelling older adults (65% male; mean age = 66.5 years). All participants were administered an extensive neuropsychological battery composed of measures of attention, executive function, memory, and visuospatial function. A subset of 99 participants also underwent magnetic resonance imaging (MRI). MMSE test-retest reliability was examined among 65 participants who underwent repeat MMSE testing over an average interval of 83.2 days. Results: Spearman test-retest correlation for total MMSE scores was r S = .35 (p = .004), for Serial Sevens was r S = .40 (p = .001), and for Word Recall was r S = −.01 (p = .96). Total MMSE performance correlated significantly with a minority of neuropsychological tests and MRI-derived indices of white matter disease and brain atrophy. A subset of 17% of participants demonstrated inappropriate intrusion of MMSE Pentagon Copy during another test of visuospatial recall. Conclusions: Overall, MMSE scores exhibited ceiling effects, poor test-retest reliability, limited sensitivity to subtle brain abnormalities, and a high rate of intrusion elsewhere in the neuropsychological battery. Individual MMSE items demonstrated poor construct validity. These qualities illustrate the serious limitations of the MMSE in detecting individual differences in cognitive function among healthy older adults.

Cardiorespiratory Fitness and Accelerated Cognitive Decline With Aging

BACKGROUND Growing evidence suggests that self-reported physical activity accounts for variability in cognitive function among older adults, and aerobic intervention may improve cognitive function in this population. However, much less is known about the longitudinal association between direct measures of cardiorespiratory fitness and cognitive function across the life span. The present study examined the prospective association between symptom-limited maximal oxygen consumption (VO2max) and longitudinal performance on a comprehensive neuropsychological battery. METHODS Up to 1,400 participants aged 19-94 years underwent initial VO2max assessment and completed subsequent tests of memory, attention, perceptuomotor speed, language, and executive function, in addition to cognitive screening measures, on up to six occasions (mean, M = 2; standard deviation, SD = 1) for up to 18 years (M = 7, SD = 3). Mixed-effects regression models were adjusted for demographic, biomedical, and behavioral confounders. RESULTS Analyses revealed significant longitudinal associations between baseline VO2max and trajectory of performance on multiple measures of verbal and visual memory, as well as on a cognitive screening test (all ps < .05). Individuals with lower VO2max demonstrated accelerated trajectories of cognitive decline over time. CONCLUSIONS Baseline cardiorespiratory fitness is related to longitudinal neuropsychological performance, and memory appears to be a particularly vulnerable domain. Evidence that aerobic fitness is associated with accelerated cognitive decline emphasizes the possible importance of behavioral interventions to optimize cognitive aging over time.

Nonsteroidal anti-inflammatory drugs, aspirin, and cognitive function in the Baltimore Longitudinal Study of Aging

OBJECTIVES: To examine the relations between the use of nonaspirin, nonsteroidal anti‐inflammatory drugs (NSAIDs) and aspirin and age‐related change in multiple domains of cognitive function in community‐dwelling individuals without dementia.

Neurocognitive Function and Cardiovascular Disease

Cardiovascular (CV) diseases and their risk factors negatively impact the brain and neurocognitive function prior to stroke, dementia, or mild cognitive impairment (MCI). Indeed, a progression of neurocognitive and neurobiological impairments may be associated with increasingly severe manifestations of CV risk and disease. In samples ranging from children to elderly, a broad spectrum of CV risk factors, and both subclinical and clinical CV diseases, have been related to decrements in cognitive function and cognitive decline across multiple domains of performance including executive functions, attention, learning and memory, perceptuo-motor speed, and others. In contrast to the MCI literature, the possibility of distinct subgroups has not been explored. Further, it remains unknown whether neurocognitive performance (or its pattern) per se can predict conversion to MCI and later dementia. We suggest that neurocognitive function may contribute to such prediction in concert with relevant radiological, genetic, biomedical, sociodemographic, and other data. To best do so, future research would benefit from inclusion of a breadth of neurocognitive tests that tap multiple domains of function and have historical sensitivity to vascular and neurodegenerative pathology, in addition to biological or radiological assessment of such pathology. Aggressive efforts at prevention and early intervention with CV risk may play a critical role in the prevention of MCI or dementia.

Depressive symptoms are associated with subclinical cerebrovascular disease among healthy older women, not men.

BACKGROUND Associations among diagnosed unipolar depression, depressive symptoms, and cerebrovascular disease are well known. However, minimal research has investigated whether sex may modify such associations, despite known sex differences in depression and depressive symptoms. This study examined whether depressive symptoms were disproportionately related to subclinical cerebrovascular disease (SCD) in women versus men. METHODS One hundred one older adults (58% men; mean age = 67 years), free of major comorbidities, completed the Beck Depression Inventory and underwent magnetic resonance imaging (MRI). MRI scans were neuroradiologist rated for markers of SCD (periventricular and deep white matter hyperintensities, and number of silent infarcts) and brain atrophy (ventricular enlargement and sulcal widening). Two rank-sum outcome variables (SCD and brain atrophy) were then created. RESULTS On average, depressive symptoms were relatively low in magnitude (mean = 3.8, standard deviation = 3.6, range = 0-17). Multiple regression analyses, adjusted for age, sex, education, systolic blood pressure, fasting glucose, maximal oxygen consumption, body mass index, average weekly alcohol consumption, and Mini-Mental State Examination performance revealed sex to be a significant effect modifier of depressive symptoms in the prediction of SCD. Sex-stratified regression analyses indicated depressive symptoms, and SCD was strongly related among women but not men. Depressive symptoms were not related to brain atrophy, regardless of inclusion of sex as an effect modifier. CONCLUSIONS Depressive symptoms, even in a subclinical range, are significantly associated with an MRI-derived index of SCD among women, but not men, in the present sample of relatively healthy older adults.

Greater Coffee Intake in Men Is Associated With Steeper Age-Related Increases in Blood Pressure

BACKGROUND Administration of caffeine or caffeinated coffee in laboratory and ambulatory settings results in small to moderate acute increases in blood pressure (BP). However, habitual coffee intake has not been linked conclusively to long-term increases in basal BP, and findings are inconsistent by sex. This study examined longitudinal relations of habitual coffee use to resting BP and pulse pressure. METHODS In a sample of 2,442 participants from the Baltimore Longitudinal Study of Aging (BLSA), coffee consumption was used to predict resting systolic and diastolic BP and pulse pressure using longitudinal mixed-effects regression models adjusted for age, education, antihypertensive, and antihyperlipidemic use, smoking, and body mass index (BMI). Analyses were stratified by sex (865 women and 1,577 men), and age and BMI were examined as possible effect modifiers. RESULTS In men, we identified a significant three-way interaction among coffee intake (nonlinear), baseline age, and length of follow-up for systolic BP (SBP) and pulse pressure. A significant interaction of coffee intake and BMI (nonlinear) was also noted for SBP in men. There were no significant relations of coffee intake to BP or pulse pressure in women. CONCLUSION Greater coffee intake in men was associated with steeper age-related increases in SBP and pulse pressure, particularly beyond 70 years of age and in overweight to obese men.

Interactive relations of blood pressure and age to subclinical cerebrovascular disease.

Objective: To examine interactive relations of blood pressure (BP) and age to MRI indices of subclinical cerebrovascular disease in middle-aged to older adults. Methods: One hundred and thirteen stroke-free and dementia-free, community-dwelling adults (ages 54–81 years; 65% men; 91% white) engaged in (1) clinical assessment of resting SBP and DBP; (2) MRI rated for periventricular white matter hyperintensities (WMH) and deep WMH silent brain infarction (SBI) and brain atrophy (i.e. ventricular enlargement and sulcal widening ). Principal components analysis of the MRI ratings yielded a two-component solution – (1) periventricular and deep WMH SBI; and (2) ventricular enlargement, sulcal widening. Results: Relations of SBP, DBP and pulse pressure (PP) (and their interactions with age) to each MRI component were examined in multiple regression analyses adjusted for age, sex, fasting plasma glucose and cholesterol, and antihypertensives. For component 1, results indicated significant interactions of SBP and PP with age (P < 0.05); higher levels of SBP and PP were associated with greater white matter disease and brain infarction at younger ages (⩽68 years). Significant interactions of SBP and DBP with age were also noted for component 2 (P < 0.05); higher levels of BP were associated with greater brain atrophy at younger ages (⩽63 years). Conclusion: Higher BP and PP are associated with greater subclinical cerebrovascular disease most prominently in the ‘young old’. Appropriate management of hypertension and arterial stiffening may be critical to the preservation of brain structure with ageing.

Renal Function and Long-Term Decline in Cognitive Function: The Baltimore Longitudinal Study of Aging

Background: Renal disease has been associated with greater risk of dementia and greater cognitive impairment. However, the relationship of lower renal function with long-term decline in specific domains of cognitive function remains unclear among community-dwelling, non-demented individuals. Methods: Stroke- and dementia-free participants (n = 2,116) were enrolled in the Baltimore Longitudinal Study of Aging, a community-based, prospective, longitudinal study. Renal function was estimated by the inverse of serum creatinine adjusted for age, sex and race and (in sensitivity analyses) estimated glomerular filtration rate (eGFR) using the MDRD formula. Outcome measures were changes in scores on 6 cognitive tests encompassing a range of cognitive functions, measured at 2-year intervals. Mixed-effects regression models examined the longitudinal relations of renal function with cognitive functions after adjusting for demographics, comorbidity and other potential confounders. Results: Mean age at initial testing was 53.9 years (SD 17.1), and 94 participants (4.4%) had an eGFR <60 ml/min/1.73 m2 and 18.5% had at least one comorbidity. With increasing age, longitudinal increases in creatinine concentrations were associated with more rapid decline in performance on several cognitive measures, including the learning slope of the California Verbal Learning Test, a test of verbal learning (p < 0.01), and the Benton Visual Retention Test, a test of visual memory (p < 0.01). Associations were similar for changes in eGFRMDRD, which was also associated with the rate of decline in verbal memory. Conclusion: In a community-based adult population, declines in renal function independently associated with greater long-term declines in visual memory and verbal memory and learning.