María J. Marquine

Neurocognitive Change in the Era of HIV Combination Antiretroviral Therapy: The Longitudinal CHARTER Study

BACKGROUND Human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) can show variable clinical trajectories. Previous longitudinal studies of HAND typically have been brief, did not use adequate normative standards, or were conducted in the context of a clinical trial, thereby limiting our understanding of incident neurocognitive (NC) decline and recovery. METHODS We investigated the incidence and predictors of NC change over 16-72 (mean, 35) months in 436 HIV-infected participants in the CNS HIV Anti-Retroviral Therapy Effects Research cohort. Comprehensive laboratory, neuromedical, and NC assessments were obtained every 6 months. Published, regression-based norms for NC change were used to generate overall change status (decline vs stable vs improved) at each study visit. Survival analysis was used to examine the predictors of time to NC change. RESULTS Ninety-nine participants (22.7%) declined, 265 (60.8%) remained stable, and 72 (16.5%) improved. In multivariable analyses, predictors of NC improvements or declines included time-dependent treatment status and indicators of disease severity (current hematocrit, albumin, total protein, aspartate aminotransferase), and baseline demographics and estimated premorbid intelligence quotient, non-HIV-related comorbidities, current depressive symptoms, and lifetime psychiatric diagnoses (overall model P < .0001). CONCLUSIONS NC change is common in HIV infection and appears to be driven by a complex set of risk factors involving HIV disease, its treatment, and comorbid conditions.

Semantic and self-referential processing of positive and negative trait adjectives in older adults

The beneficial effects of self-referential processing on memory have been demonstrated in numerous experiments with younger adults but have rarely been studied in older individuals. In the present study we tested young people, younger-older adults, and older-older adults in a self-reference paradigm, and compared self-referential processing to general semantic processing. Findings indicated that older adults over the age of 75 and those with below average episodic memory function showed a decreased benefit from both semantic and self-referential processing relative to a structural baseline condition. However, these effects appeared to be confined to the shared semantic processes for the two conditions, leaving the added advantage for self-referential processing unaffected These results suggest that reference to the self engages qualitatively different processes compared to general semantic processing. These processes seem relatively impervious to age and to declining memory and executive function, suggesting that they might provide a particularly useful way for older adults to improve their memories.

The veterans aging cohort study index is associated with concurrent risk for neurocognitive impairment.

Objective:The Veterans Aging Cohort Study (VACS) Index is predictive of mortality and combines age, traditional HIV biomarkers (HIV-1 plasma RNA and current CD4 count), and non-HIV biomarkers (indicators of renal and liver function, anemia, and hepatitis C coinfection). We examined the association between the VACS Index and HIV-associated neurocognitive impairment (NCI). Design and Methods:Participants included 601 HIV-infected adults enrolled in cohort studies at the University of California, San Diego, HIV Neurobehavioral Research Program (ages: 18–76 years; 88% male; 63% white; median current CD4 = 364 cells/mm3; 63% on antiretroviral therapy; AIDS = 64%). Biomarkers used in calculating the VACS Index were measured in prospectively collected blood samples using conventional laboratory methods. NCI was defined using global and seven domain deficit scores. Results:Higher VACS Index scores were associated with concurrent risk for global NCI [P < 0.001; odds ratio = 1.21, confidence interval (CI): 1.12 to 1.32], even when adjusting for psychiatric comorbidities. This relation was statistically significant for most cognitive domains in adjusted models. Furthermore, the VACS Index predicted concurrent NCI beyond nadir CD4 and estimated duration of infection. Older age, lower hemoglobin, and lower CD4 counts were the VACS components most strongly linked to NCI. Conclusions:The findings extend previous research on the potential usefulness of the VACS Index in predicting HIV-associated outcomes to include NCI. Although the effect size was relatively small, our findings suggest that demographic information, HIV-disease factors, and common comorbidities might each play important roles in the clinical manifestation of cognitive impairment among HIV-infected individuals. Additional research is needed to determine if a more sensitive and specific index can be developed.

Differential Patterns of Cognitive Decline in Anterior and Posterior White Matter Hyperintensity Progression

Background and Purpose— White matter hyperintensities (WMHs) found on brain MRI in elderly individuals are largely thought to be due to microvascular disease, and its progression has been associated with cognitive decline. The present study sought to determine patterns of cognitive decline associated with anterior and posterior WMH progression. Methods— Subjects included 110 normal controls, aged ≥60 years, who were participants in the Duke Neurocognitive Outcomes of Depression in the Elderly study. All subjects had comprehensive cognitive evaluations and MRI scans at baseline and after 2 years. Cognitive composites were created in 5 domains: complex processing speed, working memory, general memory, visual-constructional skills, and language. Change in cognition was calculated using standard regression-based models accounting for variables known to impact serial testing. A semiautomated segmentation method was used to measure WMH extent in anterior and posterior brain regions. Hierarchical multiple linear regression models were used to evaluate which of the 5 measured cognitive domains was most strongly associated with regional (anterior and posterior) and total WMH progression after adjusting for demographics (age, sex, and education). Results— Decline in complex processing speed was independently associated with both anterior (r2=0.06, P=0.02) and total WMH progression (r2=0.05, P=0.04). In contrast, decline in visual-constructional skills was uniquely associated with posterior progression (r2=0.05, P<0.05). Conclusions— Distinct cognitive profiles are associated with anterior and posterior WMH progression among normal elders. These differing profiles need to be considered when evaluating the cognitive correlates of WMHs.

Life Experience and Demographic Influences on Cognitive Function in Older Adults

OBJECTIVE We examined the influence of a broad spectrum of life experiences on longitudinal cognitive trajectories in a demographically diverse sample of older adults. METHOD Participants were 333 educationally, ethnically, and cognitively diverse older adults enrolled in a longitudinal aging study. Mixed-effects regression was used to measure baseline status in episodic memory, executive functioning, and semantic memory and change in a global cognition factor defined by change in these 3 domain-specific measures. We examined effects of life experience variables (literacy, childhood socioeconomic status, morphometric measures of physical development, life course physical and recreational activity) on longitudinal cognitive trajectories, covarying for age, apolipoprotein E (APOE) genotype and demographics (education, ethnicity, language). RESULTS Non-Latino Whites had higher baseline cognition, but life experience variables attenuated ethnic differences in cognitive scores. Age, literacy, childhood socioeconomic status, and physical activity significantly influenced baseline cognition. Age, APOE ε4, and decline in intellectually and socially stimulating recreational activity from mid to late life were independently associated with increased late life cognitive decline. Higher literacy and late life recreational activity were associated with less decline. Literacy had similar effects for English and Spanish readers/speakers. Bilingual English and Spanish speakers did not differ from English Speakers in cognitive performance. CONCLUSIONS Life experience variables, especially literacy level, were strongly related to baseline cognition and substantially attenuated effects of race/ethnicity and education. Cognitive change was best explained by age, APOE ε4, literacy, and current recreational activities. Literacy had robust associations with baseline cognition and cognitive change in both English and Spanish speakers.

Repeatable Battery for the Assessment of Neuropsychological Status Effort Index Performance in a Medically Ill Geriatric Sample

Using a sample of 44 clinically referred, non-litigating, older adults, we evaluated the Repeatable Battery for the Assessment of Neuropsychological Status Effort Index [RBANS EI; Silverberg, N. D., Wertheimer, J. C., & Fichtenberg, N. L. (2007). An effort index for the Repeatable Battery for the Assessment of Neurospcyhological Status (RBANS). The Clinical Neuropsychologist, 21, 841-854]. With the current RBANS EI cut-score guidelines, 31% of our sample was classified as putting forth suspect effort. With this, cognitive ability was significantly correlated with suspect effort scores. Thus, it appears that the current guidelines may not be useful in a cognitively impaired medically ill geriatric sample. Hence, further research on RBANS EI validation is warranted.

Early Life Development in a Multiethnic Sample and the Relation to Late Life Cognition

OBJECTIVES Poor quality of early life conditions has been associated with poorer late life cognition and increased risk of dementia. Early life physical development can be captured using adult measures of height and head circumference. Availability of resources may be reflected by socioeconomic indicators, such as parental education and family size. We sought to determine the association between early life development and experience and late life semantic memory, episodic memory, and executive functioning abilities, as well as rate of cognitive decline. METHOD This study was conducted using the UC Davis Aging Diversity cohort, an ethnically diverse sample of Caucasian, African American, and Hispanic individuals from northern California. We used latent variable modeling to measure growth and childhood socioeconomic environment (SES) and examine their associations with longitudinal cognitive outcomes using mixed effects modeling. RESULTS Growth was positively related to higher childhood SES. Higher childhood SES was associated with better semantic memory. Both low growth and low SES were associated with increased rate of cognitive decline. DISCUSSION These findings demonstrate that early life experiences influence the trajectory of cognitive aging. Early life development and experience appears to provide a distal basis upon which additional risk and protective factors interact in the development of dementia.

Association between Cognitive Activity and Cognitive Function in Older Hispanics

There is limited research on the association between participation in cognitively stimulating activity and cognitive function in older Hispanics. The main purpose of the present study was to explore whether frequency of cognitive activity and its association with cognitive function in Hispanics is comparable to that of non-Hispanics. In a multiethnic cohort of 1571 non-demented older adults, we assessed past and current cognitive activity, availability of cognitive resources in the home in childhood and middle age, and five domains of cognitive function. The measures of cognitive activity and cognitive resources had adequate reliability and validity in our subset of Hispanic participants (n = 81). Hispanics reported lower levels of education, lower frequency of cognitive activity and less cognitive resources than non-Hispanic White (n = 1102) and non-Hispanic Black (n = 388) participants. Despite these differences the strength of the association between cognitive activity and cognitive function was comparable across ethnic groups. Because Hispanics have lower frequency of cognitive activity, the benefit of cognitive activity to late life cognitive function may be potentially larger in this segment of the population. Thus, interventions aimed at increasing frequency of participation in cognitively stimulating activity may offer a potential target to reduce cognitive impairment in Hispanics.

Differences in Life Satisfaction among Older Community-Dwelling Hispanics and non-Hispanic Whites

Objectives: Hispanics are the fastest growing ethnic/racial group of the older adult population in the United States, yet little is known about positive mental health in this group. We examined differences in life satisfaction between demographically matched groups of older Hispanics and non-Hispanic Whites, and sought to identify specific factors associated with these differences Methods: Participants included 126 community-dwelling English-speaking Hispanics aged 50 and older, and 126 age-, gender-, and education-matched non-Hispanic Whites. Participants completed standardized measures of life satisfaction and postulated correlates, including physical, cognitive, emotional and social functioning, as well as positive psychological traits and religiosity/spirituality. Results: Hispanics reported greater life satisfaction than non-Hispanic Whites (p < 0.001). Ethnic groups were comparable on most postulated correlates of life satisfaction, except that Hispanics had lower levels of cognitive performance, and higher levels of daily spiritual experiences, private religious practices and compassion (ps < 0.001). Among these factors, spiritual experiences, religious practices, and compassion were significantly associated with life satisfaction in the overall sample. Multivariable analyses testing the influence of these three factors on the association between ethnicity and life satisfaction showed that higher spirituality among Hispanics accounted for ethnic differences in life satisfaction. Conclusion: English-speaking Hispanics aged 50 and older appeared to be more satisfied with their lives than their non-Hispanic White counterparts, and these differences were primarily driven by higher spirituality among Hispanics. Future studies should examine positive mental health among various Hispanic subgroups, including Spanish speakers, as an important step toward development of culturally sensitive prevention and intervention programs aimed at promoting positive mental health.

Life satisfaction and its correlates among older cancer survivors: critical role of psychosocial factors

Dear Editor,IntroductionImprovements in early detection and treatment of cancerhave resulted in a growing number of aging cancer survi-vors. Currently, 60% of the 10 million cancer survivors inthe USA are older than 65 years [1]. Yet, research hasbeen scarce on mental health outcomes, especially satis-faction with life (SWL), in older cancer survivors (OCSs)[2]. A number of existing studies in this arena are limitedby a focus on a single cancer type such as breast cancer,small sample sizes, inclusion of people with very recentlydiagnosed cancer, and a lack of age-matched healthycomparison subjects (HCs) [1–3]. There are also prevalentassumptions that limit progress in our understanding ofpsychological well-being in this population, for example,that positive emotions are absent, dangerous, delusional,or trivial among people with life-threatening illnesses[4]. Studiessuggestthat OCSsfare muchworse physicallythan HCs as a result of adverse interactions among cancer,its treatment, aging, and comorbidity [1–3]. Findings onmental function suggest that OCSs have worse psycholog-ical functioning than HCs [1], experience age-associateddecline in health-related quality of life [5], and have loweroptimism about life expectancy than HCs [3]. Other find-ings are mixed, with some studies reporting similar de-pression scores and cognitive function between OCSsand HCs [3], whereas others report increased depressionwith age but no association between age and SWL inOCSs [2]. Conversely, OCSs have reported resilient socialwell-being, spirituality, and personal growth with aging[6]. Notably, only a few reports have employedstandardized instruments for assessing positive psychoso-cialresourcessuchas SWL,resilience,optimism,personalmastery, and spirituality [2].Thus,understandingSWLanditspsychosocialcorrelatesamong OCSs remains an important but understudied areawith high public health significance. Such research wouldbe of value in developing interventions to increase SWL.The present study compared SWL, as well as health-related physical, cognitive, and psychosocial functioninginOCSs,withthatindemographicallymatchedHCsfroma community-based sample. As several studies havereported worse physical and psychological function inOCSs than among HCs [1], we hypothesized that OCSswould perform worse in all spheres of functioningcompared with HCs. We also examined the correlates ofSWL in the two groups.Materials and methodsParticipantsCancer survivors and HCs were recruited from a largemulticohortlongitudinal,community-basedsampleofolderadults whohad beenselected using random digit dialing, inthe Successful AGing Evaluation (SAGE) study. TheSAGEdataincludestandardizedmeasuresofphysical,cog-nitive,andpsychosocialfunctioningfromatelephoneinter-view and a mail-in survey completed by 1006 participantsbetween the ages of 50 and 99 years [7]. Two hundredandnineteenSAGEparticipantsreportedhavingadiagnosisof cancer (excluding skin cancer). They were comparedwith 219 age-, gender-, and education-matched HCs fromthe same sample, who did not report a history of cancer.