Arlener D. Turner

Cytomegalovirus Infection and Risk of Alzheimer Disease in Older Black and White Individuals

BACKGROUND Human cytomegalovirus (CMV) is prevalent in older adults and has been implicated in many chronic diseases of aging. This study investigated the relation between CMV and the risk of Alzheimer disease (AD). METHODS Data come from 3 cohort studies that included 849 participants (mean age [±SD], 78.6 ± 7.2 years; mean education duration [±SD], 15.4 ± 3.3 years; 25% black). RESULTS A solid-phase enzyme-linked immunosorbent assay was used for detecting type-specific immunoglobulin G antibody responses to CMV and herpes simplex virus type 1 (HSV-1) measured in archived serum samples. Of 849 participants, 73.4% had serologic evidence of exposure to CMV (89.0% black and 68.2% white; P < .001). During an average of 5.0 years of follow-up, 93 persons developed AD. CMV seropositivity was associated with an increased risk of AD (relative risk, 2.15; 95% confidence interval, 1.42-3.27) and a faster rate of decline in global cognition (estimate [±standard error], -0.02 ± 0.01; P = .03) in models that controlled for age, sex, education duration, race, vascular risk factors, vascular diseases, and apolipoprotein ε4 level. Results were similar in black and white individuals for both incident AD and change in cognitive function and were independent of HSV-1 status. CONCLUSIONS These results suggest that CMV infection is associated with an increased risk of AD and a faster rate of cognitive decline in older diverse populations.

Physical activity, motor function, and white matter hyperintensity burden in healthy older adults

Objective: To test the hypothesis that physical activity modifies the association between white matter hyperintensity (WMH) burden and motor function in healthy older persons without dementia. Methods: Total daily activity (exercise and nonexercise physical activity) was measured for up to 11 days with actigraphy (Actical; Philips Respironics, Bend, OR) in 167 older adults without dementia participating in the Rush Memory and Aging Project. Eleven motor performances were summarized into a previously described global motor score. WMH volume was expressed as percent of intracranial volume. Linear regression models, adjusted for age, education, and sex, were performed with total WMH volume as the predictor and global motor score as the outcome. Terms for total daily physical activity and its interaction with WMH volume were then added to the model. Results: Higher WMH burden was associated with lower motor function (p = 0.006), and total daily activity was positively associated with motor function (p = 0.002). Total daily activity modified the association between WMH and motor function (p = 0.007). WMH burden was not associated with motor function in persons with high activity (90th percentile). By contrast, higher WMH burden remained associated with lower motor function in persons with average (50th percentile; estimate = −0.304, slope = −0.133) and low (10th percentile; estimate = −1.793, slope = −0.241) activity. Conclusions: Higher levels of physical activity may reduce the effect of WMH burden on motor function in healthy older adults.

Depressive Symptoms and Cognitive Decline in Older African Americans: Two Scales and Their Factors

OBJECTIVE Depressive symptoms are common in older adults, and researchers have explored the possibility of a link between depressive symptoms and cognitive decline, with mixed results. Most studies use total score of the Center for Epidemiological Studies Depression Scale (CES-D) with predominately non-Hispanic white participants. We sought to examine the relationship between the four factors of the CES-D and cognitive decline in older African Americans. Generalizability was determined using the Geriatric Depression Scale (GDS) and its factors. METHODS Participants without dementia from the Minority Aging Research Study (N = 298, mean age: 74 ± 5.68) underwent annual clinical evaluations (mean years: 5 ± 1.9), including depression assessment and cognitive testing, from which global and specific measures were derived. Cognitive decline was examined with linear mixed models adjusted for demographic variables and indicators of vascular risk. RESULTS Total CES-D score was not related to baseline cognition or change over time, whereas total GDS score was related to decline in semantic and working memory. In examining CES-D factors, lack of positive affect (e.g., anhedonia) was related to decline in global cognition, episodic memory, and perceptual speed. Similarly for the GDS, anhedonia was associated with decline in semantic memory, and increased negative affect was associated with decline in global cognition and episodic, semantic, and working memory. CONCLUSION Results suggest that depressive symptoms, particularly anhedonia and negative affect, are related to cognitive decline in older African Americans.

Depressive symptomatology and respiratory sinus arrhythmia in a non-clinical sample of middle-aged African Americans

Decreased heart rate variability and depression are both independent risk factors for cardiac mortality in clinical and non-clinical samples. The purpose of the current study is to examine the hypothesis that severity of depressive symptomatology is inversely associated with respiratory sinus arrhythmia (RSA) in a non-clinical sample of African Americans. The sample included 77 African Americans with a mean age of 48.4 (SD = 11.7). Participants completed the Beck Depression Inventory-II (BDI-II) and a 5-min resting baseline measurement of RSA was collected. The BDI-II total score was positively associated with RSA (β = .334, p = .008). Given the unexpected direction of the association, we separated the BDI-II into cognitive and somatic affective subscales to identify which construct was driving the relationship. The somatic affective, was related to RSA (β = .328, p = .010), but not the cognitive subscale. Given this unexpected positive result, future research should further examine the nature of the relationship between depressive symptomatology and RSA in African Americans, as the relationship may vary based on levels of depressive symptomatology.

Perceived Stress and Cognitive Decline in Different Cognitive Domains in a Cohort of Older African Americans

BACKGROUND Research indicates that stress is linked to cognitive dysfunction. However, few community-based studies have explored the relationship between perceived stress and cognitive decline, and fewer still have utilized cognitive domains rather than a global measure of cognition. OBJECTIVE We examined the relation between perceived stress and the rate of decline in different cognitive domains. METHODS Participants were older African Americans without dementia from the Minority Aging Research Study (MARS; N = 467, mean age: 73 years, SD: 6.1 years). A battery of 19 cognitive tests was administered at baseline and at annual intervals for up to 9 years (mean follow-up: 4 years), from which composite measures of global cognitive function and five specific cognitive domains were derived. The four-item Cohens Perceived Stress Scale (PSS) was also administered at baseline. RESULTS In linear mixed-effects models adjusted for age, sex, education, and vascular risk factors, higher perceived stress was related to faster declines in global cognition (β = -0.019; SE: 0.008; t(1951) = -2.46), episodic memory (β = -0.022; SE: 0.011; t(1954) = -1.99), and visuospatial ability (β = -0.021; SE: 0.009; t(1939) = -2.38) all p < 0.05. Findings were similar in subsequent models adjusted for demographics, vascular diseases, and depressive symptoms. CONCLUSIONS Results indicate that older African Americans with higher levels of perceived stress have more rapid declines in global cognition than those with lower levels, most notably for episodic memory and visuospatial ability.

Evaluating the treatment of obstructive sleep apnea comorbid with insomnia disorder using an incomplete factorial design

Chronic insomnia disorder is a prevalent condition and a significant proportion of these individuals also have obstructive sleep apnea (OSA). These two sleep disorders have distinct pathophysiology and are managed with different treatment approaches. High comorbidity rates have been a catalyst for emerging studies examining multidisciplinary treatment for OSA comorbid with insomnia disorder. In this article, we describe a randomized clinical trial of cognitive behavioral treatment for insomnia (CBT-I) and positive airway pressure (PAP) for OSA. Participants are randomized to receive one of three treatment combinations. Individuals randomized to treatment Arm A receive sequential treatment beginning with CBT-I followed by PAP, in treatment Arm B CBT-I and PAP are administered concurrently. These treatment arms are compared to a control condition, treatment Arm C, where individuals receive PAP alone. Adopting an incomplete factorial study design will allow us to evaluate the efficacy of multidisciplinary treatment (Arms A & B) versus standard treatment alone (Arm C). In addition, the random allocation of individuals to the two different combined treatment sequences (Arm A and Arm B) will allow us to understand the benefits of the sequential administration of CBT-I and PAP relative to concurrent treatment of PAP and CBT-I. These findings will provide evidence of the clinical benefits of treating insomnia disorder in the context of OSA.

Association between interleukin-6 and neurocognitive performance as a function of self-reported lifetime marijuana use in a community based sample of African American adults.

The purpose of the current study was to determine if self-reported lifetime marijuana use moderates the relationship between interleukin-6 (IL-6) and neurocognitive performance. Participants included 161 African American adults (50.3% women), with a mean age of 45.24 (SD=11.34). Serum was drawn upon entry into the study and participants completed a demographic questionnaire, which included drug use history, and a battery of neuropsychological tests. Using multiple regression analyses and adjusting for demographic covariates, the interaction term comprised of IL-6 and self-reported lifetime marijuana use was significantly associated with poorer performance on the Written (β=-.116; SE=.059; p=.049) and Oral trials (β=-.143; SE=.062; p=.022) of the Symbol Digit Modalities Test, as well as the Trail Making Test trial A (β=.157; SE=.071; p=.028). Current findings support previous literature, which presents the inverse relationship between IL-6 and neurocognitive dysfunction. The potential protective properties of marijuana use in African Americans, who are at increased risk for inflammatory diseases, are discussed.

Reply to Itzhaki

To the Editor—We thank Drs Itzhaki and Klapper for their interest in and comments regarding our study [1], which examined the relationship between cytomegalovirus (CMV) infection and risk of Alzheimers disease (AD). We found that CMV seropositivity was associated with a 2-fold increase in risk of AD and a faster rate of cognitive decline. The results were robust to a number of covariates, including herpes simplex virus type 1 (HSV-1). In addition, our findings support earlier cohort studies that have examined the association between CMV and cognitive function [2, 3]. Together, these studies suggest a potential role for CMV as a factor that may influence cognition and risk of AD in older ages. As Itzhaki and Klapper state, one must use assays of equivalent sensitivity when comparing serological evidence of past exposure to HSV-1 with that of CMV. We agree. Although the assays used for immunoglobin G antibodies to CMV and HSV-1 were different in antigenic composition, both have been widely used in epidemiologic studies in different populations. We reported that rates of positivity for HSV-1 in our sample were much lower than for CMV, and that this discrepancy might be a reason for the lack of associations with HSV-1. Few large epidemiologic studies with older adults have specifically addressed HSV-1 [4]. Nonetheless, the lack of an association between HSV-1 antibodies and AD in our study does not preclude a role for HSV-1 in some cases of AD, using more sensitive immunological or virologic methods. The authors state that our findings contrast with others who have found a relationship between HSV-1 and cognitive decline. However, the studies cited are cross-sectional rather than longitudinal, which is needed to document cognitive decline, and most were small case-control studies of HSV-1 in the brain. Thus, the association of HSV-1 and incident AD remains unknown at this time. Overall, the evidence points to a role for herpesvirus infections in some cases of AD. Indeed, identifying an association between CMV and AD supports the hypothesis that herpesviruses may play an important role in disease risk, and does not negate a potential role for other pathogens in AD. A better understanding of the role of individual infectious agents or their combination will require large-scale studies involving different populations and, ultimately, intervention studies using specific prevention and treatment modalities.

The Psychoneuroimmunological Influences of Recreational Marijuana

Background: Marijuana is the most widely used illicit substance in the USA and self-reported use has remained steady over the past decade. Numerous publications examine the influence of marijuana use on various facets of human physiology including neurocognitive function, immune function, and illness symptom control, each discussing marijuana’s influence in a narrow or compartmentalized fashion. However, there is a scant literature discussing the empirical and clinical implications of the intersection of these constructs. The primary objective of this review is to review and synthesize this disparate literature and propose future research directions. Thus, this review examines the literature that relates the influence of marijuana to: (1) neurocognitive function; (2) immune function; (3) treatment uses; and (4) propose future directions.