Cognition and Functional Capacity: An Initial Comparison of Veteran and Non-Veteran Older Adults.

INTRODUCTION: The U.S. Military Veterans aged 65 and older comprise an estimated 43% of the 22 million living Veterans in the United States. Veterans have high rates of physical, psychiatric, and social challenges, but it is not known whether Veteran status confers additional risk for cognitive or functional impairments in later life. Thus, this investigation specifically compared older Veterans with their non-Veteran peers in cognitive functioning and performance-based functional capacity. MATERIALS AND METHODS: Participants (N = 110; 29 Veterans and 81 non-Veterans) were part of a larger longitudinal study on biopsychosocial functioning in independently living older adult residents of a Continuing Care Senior Housing Community. The University of California San Diego Institutional Review Board approved the study and all participants provided written informed consent. Participants provided demographic and mental health information and were administered a comprehensive neuropsychological battery. Functional capacity was assessed using the UCSD Performance-Based Skills Assessment-Brief (UPSA-B), which uses financial and communication role-plays to assess everyday functioning skills. Neuropsychological scores were appropriately normed prior to analysis. Multivariate Analyses of Variances with post hoc t-tests and an Analysis of Covariance were used to examine neuropsychological and functional capacity differences, respectively, between Veterans and non-Veterans. RESULTS: Veterans did not differ from non-Veterans in educational attainment (16.4 years versus 15.5 years, P = 0.110), but they were significantly older (mean age 86.9 years ± 5.7, versus 81.74 years ± 6.53; P < 0.001) and were more likely to be male (X2 [1, N = 110] = 62.39, P < 0.001). Thus, though neuropsychological norms already accounted for demographic differences in our participants, age and sex were controlled in the Analysis of Covariance predicting UPSA-B score from Veteran status. Results suggested that, compared to non-Veterans, Veterans had significantly worse performance in the list learning portion of a test of verbal memory (Hopkins Verbal Learning Test-Revised, Total Recall; t = 2.56, P = 0.012, d = 0.56). Veterans and non-Veterans did not significantly differ in performance on the delayed recall portion of the verbal learning test and did not differ on a cognitive screening test (Montreal Cognitive Assessment) or on measures of premorbid intellectual functioning (Wide Range Achievement Test-4 Reading), language (Boston Naming Test, Verbal Fluency), visual memory (Brief Visuospatial Memory Test-Revised), attention/working memory (WAIS-IV Digit Span), processing speed (WAIS-IV Digit Symbol Coding), executive function (Delis-Kaplan Executive Function System Trails and Color-Word Test), or functional capacity (UPSA-B). Because our examination of multiple outcomes might have inflated Type I error, we performed a post hoc adjustment of P values using Benjamini-Hochberg procedures and the group difference in verbal learning remained significant. CONCLUSIONS: Despite largely similar function in most domains, Veterans performed significantly more poorly in verbal list learning than their non-Veteran peers. Additional attention should be given to the understanding, assessment, and possible treatment of learning and memory differences in older Veterans, as this may be an area in which Veteran status confers additional risk or vulnerability to decline. This is the first study to compare objective neuropsychological and functional performance between older (age 65+) US Veterans and non-Veterans.

Neuropsychological Correlates of PTSD and Depressive Symptom Improvement in Compensatory Cognitive Training for Veterans With a History of Mild Traumatic Brain Injury.

INTRODUCTION: Mild traumatic brain injury (mTBI), depression, and PTSD are highly prevalent in post-9/11 veterans. With the comorbidity of depression and PTSD in post-9/11 veterans with mTBI histories and their role in exacerbating cognitive and emotional dysfunction, interventions addressing cognitive and psychiatric functioning are critical. Compensatory Cognitive Training (CCT) is associated with improvements in prospective memory, attention, and executive functioning and has also yielded small-to-medium treatment effects on PTSD and depressive symptom severity. We sought to examine neuropsychological correlates of PTSD and depressive symptom improvement in veterans with a history of mTBI who received CCT. MATERIALS AND METHODS: Thirty-seven post-9/11 veterans with mTBI histories and cognitive complaints received 10 weekly 120-minute CCT group sessions. Participants completed a baseline neuropsychological assessment, including tests of premorbid functioning, attention/working memory, processing speed, verbal learning/memory, and executive functioning, and completed psychiatric symptom measures (PTSD and depression) at baseline, post-treatment, and a 5-week follow-up. Paired samples t-tests were used to examine statistically significant changes in PTSD (total and symptom cluster scores) and depressive symptom scores over time. Pearson's correlations were calculated between neuropsychological scores and PTSD and depressive symptom change scores at post-treatment and follow-up. Neuropsychological measures identified as significantly correlated with psychiatric symptom change scores were entered as independent variables in multivariable regression analyses to examine their association with symptom change at post-treatment and follow-up. RESULTS: Over 50% of CCT participants had clinically meaningful improvement in depressive symptoms (≥17.5% score reduction), and over 20% had clinically meaningful improvement in PTSD symptoms (≥10-point improvement) at post-treatment and follow-up. Examination of PTSD symptom cluster scores revealed a statistically significant improvement in avoidance/numbing at follow-up. Bivariate correlations indicated that worse baseline performance on Category Fluency was moderately associated with PTSD symptom improvement at post-treatment. Worse performance on both Category Fluency and Category Switching Accuracy was associated with improvement in depressive symptoms at post-treatment and follow-up. Worse performance on Trail-Making Number-Letter Switching was also associated with improvement in depressive symptoms at follow-up. Subsequent regression analyses revealed that worse processing speed and worse aspects of executive functioning at baseline were associated with depressive symptom improvement at post-treatment and follow-up. CONCLUSIONS: Worse baseline performances on tests of processing speed and aspects of executive functioning were significantly associated with improvements in PTSD and depressive symptoms during the trial. Our results suggest that cognitive training may bolster skills that are helpful for PTSD and depressive symptom reduction and that those with worse baseline functioning may benefit more from treatment because they have more room to improve.

Memory, fluid reasoning, and functional capacity in adults experiencing homelessness.

BACKGROUND AND OBJECTIVE: In individuals experiencing homelessness, determinants of functional capacity (i.e. the ability to perform activities of daily living) are poorly understood. Identifying potentially modifiable correlates of functional capacity, such as cognitive abilities, may inform treatment targets to address independence and housing stability. This study aimed to identify the strongest neuropsychological predictors of variance in functional performance in 100 adults living in a homeless shelter. METHODS: Participants completed a brief cognitive screening test, from which four composite scores were derived, as well as tests of processing speed, fluid reasoning, premorbid intellectual function, and performance-based functional capacity. We conducted a hierarchical linear regression to predict variance in functional capacity. RESULTS: Beyond the impact of education and premorbid intellectual function, better memory and fluid reasoning predicted better functional performance. CONCLUSIONS: Although our cross-sectional design does not permit causal inference, it is possible that interventions targeting memory and fluid reasoning may improve functional ability in individuals experiencing homelessness.

Rates of Cognitive and Functional Impairments in Older Adults Residing in a Continuing Care Senior Housing Community.

OBJECTIVE: The current cross-sectional study examined cognition and performance-based functional abilities in a continuing care senior housing community (CCSHC) that is comparable to other CCSHCs in the US with respect to residents' demographic characteristics. METHOD: Participants were 110 older adult residents of the independent living unit. We assessed sociodemographics, mental health, neurocognitive functioning, and functional capacity. RESULTS: Compared to normative samples, participants performed at or above expectations in terms of premorbid functioning, attention span and working memory, processing speed, timed set-shifting, inhibitory control, and confrontation naming. They performed below expectation in verbal fluency and verbal and visual learning and memory, with impairment rates [31.4% (>1 SD below the mean) and 18.49% (>1.5 SD below the mean)] well above the general population (16% and 7%, respectively). Within the cognitive test battery, two tests of delayed memory were most predictive of a global deficit score. Most cognitive test scores correlated with performance-based functional capacity. CONCLUSIONS: Overall, results suggest that a subset of older adults in the independent living sector of CCSHCs are cognitively and functionally impaired and are at risk for future dementia. Results also argue for the inclusion of memory tests in abbreviated screening batteries in this population. We suggest that CCSHCs implement regular cognitive screening procedures to identify and triage those older adults who could benefit from interventions and, potentially, a transition to a higher level of care.

REM Sleep Behavior Disorder in Parkinson's Disease: Change in Cognitive, Psychiatric, and Functional Outcomes from Baseline to 16-47-Month Follow-Up.

OBJECTIVE: Rapid Eye Movement Sleep Behavior Disorder (RBD) is common in Parkinson's Disease (PD) and is associated with cognitive impairment; however, the majority of the evidence on the impact of RBD on multidomain cognitive batteries in PD is cross-sectional. This study evaluated the longitudinal impact of probable RBD (pRBD) on cognitive, psychiatric, and functional outcomes in people with PD. METHOD: Case-control study. A total of 65 people with PD completed the study protocol at baseline and 16-to-47-month follow-up. Participants were classified as pRBD+ (n = 25) or pRBD- (n = 40) based on an established cutoff of 6 on the RBD Sleep Questionnaire (RBDSQ). Participants also completed a) comprehensive cognitive testing, b) self-report measures of depression, anxiety, and apathy, and c) performance-based and other-report forms of instrumental activities of daily living. RESULTS: Baseline mean age was 67.8 (SD = 8.1; range = 45-86) and baseline mean years of education was 16.4 (SD = 2.1; range = 12-20). The two groups did not differ on measured demographic characteristics. Baseline mean T-scores for cognitive tests were in the average range (46-55). Hierarchical linear models tested group differences in cognitive and functional decline from baseline to follow-up, controlling for appropriate demographic and psychiatric variables. Compared to the pRBD- group, pRBD+ participants showed greater decline in attention/working memory (r = -0.31; p = 0.01) and UPSA financial skills (r = -0.31; p = 0.01). No other group differences approached significance. CONCLUSIONS: RBD may differentially affect attention/working memory and financial abilities in PD. Results underscore the importance of regular RBD screening in older adults with PD in order to triage symptomatic patients to appropriate cognitive and medical interventions.

Rates of Cognitive and Functional Impairments Among Sheltered Adults Experiencing Homelessness.

OBJECTIVE: This study examined rates of objective cognitive and functional impairments and associations between cognitive performance and performance-based functional capacity in a well-characterized sample of adults experiencing homelessness. METHODS: One hundred participants completed a brief neuropsychological and functional capacity assessment and self-report questionnaires. Cognitive impairment rates were determined by comparing mean scores with published normative data, as well as by examining frequency of scores >1 SD below the mean. Pearson correlations were used to examine associations between cognitive and functional capacities. RESULTS: Overall, 65% of the study participants had scores in the cognitively impaired range on a brief cognitive screening test, 30% had impaired processing speed, and 11% met cognitive criteria for intellectual disability. Furthermore, 48% of the sample met functional impairment criteria, and poorer cognitive performance was strongly associated with poorer performance-based functional capacity (p<0.001). CONCLUSIONS: Cognitive and functional impairments are common among sheltered adults experiencing homelessness, underscoring the need for routine objective cognitive screening and rehabilitation services.

Home-Based Cognitively Assistive Robots: Maximizing Cognitive Functioning and Maintaining Independence in Older Adults Without Dementia.

Promoting health and prolonging independence in the home is a priority for older adults, caregivers, clinicians, and society at large. Rapidly developing robotics technology provides a platform for interventions, with the fields of physically and socially assistive robots expanding in recent years. However, less attention has been paid to using robots to enhance the cognitive health of older adults. The goal of this review is to synthesize the current literature on home-based cognitively assistive robots (CAR) in older adults without dementia and to provide suggestions to improve the quality of the scientific evidence in this subfield. First, we set the stage for CAR by: a) introducing the field of robotics to improve health, b) summarizing evidence emphasizing the importance of home-based interventions for older adults, c) reviewing literature on robot acceptability in older adults, d) highlighting important ethical issues in healthcare robotics, and e) reviewing current findings on socially assistive robots, with a focus on translating findings to the CAR context. With this foundation in place, we then review the literature on CAR, identifying gaps and limitations of current evidence, and proposing future directions for research. We conclude that CAR is promising and feasible and that there is a need for more methodologically rigorous evaluations of CAR to promote prolonged home-based independence in older adults.

Accuracy of case managers in estimating intelligence quotients and functional status of people experiencing homelessness.

Adults who are homeless experience high rates of health conditions and psychological distress, including low IQ and functional status. Resources are available to help these individuals, but provision of support is often contingent upon the identification of a known disability. In this context, we examined case managers' (CMs') subjective estimates of IQ and functional status in 77 adult residents of an urban homeless shelter. Participants completed objective measures of IQ and functional capacity. CMs overestimated IQs of lower IQ (IQ < 90) participants, correctly estimated IQs of average IQ (IQ = 90-110) participants, and underestimated IQs of higher IQ (IQ > 110) participants. CMs correctly identified 2 out of 8 participants meeting criteria for intellectual disability and 4 out of 16 participants with impaired functional status. These findings suggest that subjective evaluations of IQ and functional status are prone to a central tendency bias, leading CMs to overlook clients who are in need of assistance. Consequently, the objective measurement of IQ and functional status in homeless shelters is highly recommended. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

A tale of two stories: Validity of an alternative story memory test in a sample of older adults.

Objective: Many patients require repeat neuropsychological evaluations to determine change over time. Repeat evaluations lead to practice effects, which can impact the validity of the assessment. The current study assessed, in older adults, the validity of an alternative set of verbal memory stories created by Newcomer and colleagues.Method: A total 154 of non-demented adults, ages 60-92, completed the WMS-III logical memory (LM) stories and two Newcomer stories (Carson-Jones) as part of a larger battery of neurocognitive tests. The Carson-Jones stories were scored for: (1) verbatim (traditional) and (2) thematic (developed for this study) accuracy. Story memory variables were compared to each other and additional neurocognitive measures using bivariate correlations. A subset of participants (n = 133) completed magnetic resonance imaging (MRI) and various structural regions (e.g. thickness and volume of medial temporal lobe structures) were used to assess external validity of Carson-Jones stories with hierarchical multiple regression analyses.Results: There was a strong positive correlation between WMS-III LM and Carson-Jones stories for both verbatim and thematic scoring. Both scoring types showed convergent validity with other verbal memory measures (e.g. WMS-III LM and HVLT-R Delay/Learning) and divergent validity with Stroop Word Reading and JOLO. Regarding neuroimaging correlates, Carson-Jones verbatim scoring was significantly associated with left subiculum and left whole hippocampal volume whereas thematic scoring was significantly associated only with left subiculum.Conclusions: Newcomer stories appear to be a valid alternative to WMS-III LM stories in terms of assessing verbal memory in healthy older adults.

Threshold regression to accommodate a censored covariate.

In several common study designs, regression modeling is complicated by the presence of censored covariates. Examples of such covariates include maternal age of onset of dementia that may be right censored in an Alzheimer's amyloid imaging study of healthy subjects, metabolite measurements that are subject to limit of detection censoring in a case-control study of cardiovascular disease, and progressive biomarkers whose baseline values are of interest, but are measured post-baseline in longitudinal neuropsychological studies of Alzheimer's disease. We propose threshold regression approaches for linear regression models with a covariate that is subject to random censoring. Threshold regression methods allow for immediate testing of the significance of the effect of a censored covariate. In addition, they provide for unbiased estimation of the regression coefficient of the censored covariate. We derive the asymptotic properties of the resulting estimators under mild regularity conditions. Simulations demonstrate that the proposed estimators have good finite-sample performance, and often offer improved efficiency over existing methods. We also derive a principled method for selection of the threshold. We illustrate the approach in application to an Alzheimer's disease study that investigated brain amyloid levels in older individuals, as measured through positron emission tomography scans, as a function of maternal age of dementia onset, with adjustment for other covariates. We have developed an R package, censCov, for implementation of our method, available at CRAN.

Linear Regression with a Randomly Censored Covariate: Application to an Alzheimer's Study.

The association between maternal age of onset of dementia and amyloid deposition (measured by in vivo positron emission tomography (PET) imaging) in cognitively normal older offspring is of interest. In a regression model for amyloid, special methods are required due to the random right censoring of the covariate of maternal age of onset of dementia. Prior literature has proposed methods to address the problem of censoring due to assay limit of detection, but not random censoring. We propose imputation methods and a survival regression method that do not require parametric assumptions about the distribution of the censored covariate. Existing imputation methods address missing covariates, but not right censored covariates. In simulation studies, we compare these methods to the simple, but inefficient complete case analysis, and to thresholding approaches. We apply the methods to the Alzheimer's study.

Multiple Imputation of a Randomly Censored Covariate Improves Logistic Regression Analysis.

Randomly censored covariates arise frequently in epidemiologic studies. The most commonly used methods, including complete case and single imputation or substitution, suffer from inefficiency and bias. They make strong parametric assumptions or they consider limit of detection censoring only. We employ multiple imputation, in conjunction with semi-parametric modeling of the censored covariate, to overcome these shortcomings and to facilitate robust estimation. We develop a multiple imputation approach for randomly censored covariates within the framework of a logistic regression model. We use the non-parametric estimate of the covariate distribution or the semiparametric Cox model estimate in the presence of additional covariates in the model. We evaluate this procedure in simulations, and compare its operating characteristics to those from the complete case analysis and a survival regression approach. We apply the procedures to an Alzheimer's study of the association between amyloid positivity and maternal age of onset of dementia. Multiple imputation achieves lower standard errors and higher power than the complete case approach under heavy and moderate censoring and is comparable under light censoring. The survival regression approach achieves the highest power among all procedures, but does not produce interpretable estimates of association. Multiple imputation offers a favorable alternative to complete case analysis and ad hoc substitution methods in the presence of randomly censored covariates within the framework of logistic regression.

Maternal dementia age at onset in relation to amyloid burden in non-demented elderly offspring.

Family history (FH) of dementia is a major risk factor for Alzheimer's disease, particularly when the FH is maternal and when the age of dementia onset (AO) is younger. This study tested whether brain amyloid-beta deposition, measured in vivo with (11)C-Pittsburgh compound B (PiB), was associated with parental dementia and/or younger parental AO. Detailed FH and positron emission tomography (PiB) data were acquired in 147 nondemented aging individuals (mean age 75 ± 8). No participant had both positive maternal and paternal FH. A series of analyses revealed that those with maternal, but not paternal, FH had greater levels of PiB retention in a global cortical region than those without FH. PiB retention in maternal FH was not significantly greater than paternal FH. Younger maternal dementia AO was related to greater PiB retention in offspring, whereas younger paternal dementia AO was not. Overall, results suggest that not only is amyloid-beta burden greater in individuals with maternal FH, but also that the burden is greater in association with younger maternal AO.

Cognitive activity relates to cognitive performance but not to Alzheimer disease biomarkers.

OBJECTIVE: We aimed to determine whether there was a relationship between lifestyle factors and Alzheimer disease biomarkers. METHODS: In a cross-sectional study, we evaluated self-reported histories of recent and past cognitive activity, self-reported history of recent physical activity, and objective recent walking activity in 186 clinically normal individuals with mean age of 74 ± 6 years. Using backward elimination general linear models, we tested the hypotheses that greater cognitive or physical activity would be associated with lower Pittsburgh compound B-PET retention, greater (18)F-fluorodeoxyglucose-PET metabolism, and larger hippocampal volume, as well as better cognitive performance on neuropsychological testing. RESULTS: Linear regression demonstrated that history of greater cognitive activity was correlated with greater estimated IQ and education, as well as better neuropsychological testing performance. Self-reported recent physical activity was related to objective exercise monitoring. However, contrary to hypotheses, we did not find evidence of an association of Pittsburgh compound B retention, (18)F-fluorodeoxyglucose uptake, or hippocampal volume with past or current levels of cognitive activity, or with current physical activity. CONCLUSIONS: We conclude that a history of lifelong cognitive activity may support better cognitive performance by a mechanism that is independent of brain ß-amyloid burden, brain glucose metabolism, or hippocampal volume.

Florbetapir (F18-AV-45) PET to assess amyloid burden in Alzheimer's disease dementia, mild cognitive impairment, and normal aging.

OBJECTIVE: To evaluate the performance characteristics of florbetapir F18 positron emission tomography (PET) in patients with Alzheimer's disease (AD), mild cognitive impairment (MCI), and healthy control subjects (HCs). METHODS: Florbetapir PET was acquired in 184 subjects (45 AD patients, 60 MCI patients, and 79 HCs) within a multicenter phase 2 study. Amyloid burden was assessed visually and quantitatively, and was classified as positive or negative. RESULTS: Florbetapir PET was rated visually amyloid positive in 76% of AD patients, 38% of MCI patients, and 14% of HCs. Eighty-four percent of AD patients, 45% of MCI patients, and 23% of HCs were classified as amyloid positive using a quantitative threshold. Amyloid positivity and mean cortical amyloid burden were associated with age and apolipoprotein E ε4 carrier status. CONCLUSIONS: : The data are consistent with expected rates of amyloid positivity among individuals with clinical diagnoses of AD and MCI, and indicate the potential value of florbetapir F18 PET as an adjunct to clinical diagnosis.

Subjective cognitive complaints and amyloid burden in cognitively normal older individuals.

Accumulating evidence suggests that subjective cognitive complaints (SCC) may indicate subtle cognitive decline characteristic of individuals with preclinical Alzheimer's disease (AD). In this study, we sought to build upon previous studies by associating SCC and amyloid-ß deposition using positron emission tomography with Pittsburgh Compound B (PiB-PET) in cognitively normal older individuals. One-hundred thirty one subjects (mean age 73.5±6) were administered three subjective cognitive questionnaires and a brief neuropsychological battery. A relationship between a subjective memory complaints composite score and cortical PiB binding was found to be significant, even after controlling for depressive symptoms. By contrast, there were no significant relationships between objective cognitive measures of memory and executive functions and cortical PiB binding. Our study suggests that SCC may be an early indicator of AD pathology detectable prior to significant objective impairment.

Face-name associative memory performance is related to amyloid burden in normal elderly.

Cerebral amyloid beta (Aß) deposition occurs in a substantial fraction of cognitively normal (CN) older individuals. However, it has been difficult to reliably detect evidence of amyloid-related cognitive alterations in CN using standard neuropsychological measures. We sought to determine whether a highly demanding face-name associative memory exam (FNAME) could detect evidence of Aß-related memory impairment in CN. We studied 45 CN subjects (mean age=71.7 ± 8.8) with Clinical Dementia Rating (CDR) scores=0 and MMSE ≥ 28, using Positron Emission Tomography with Pittsburgh Compound B (PiB PET). Memory factor scores were derived from a principal components analysis for FNAME name retrieval (FN-N), FNAME occupation retrieval (FN-O) and the 6-Trial Selective Reminding Test (SRT). Using multiple linear and logistic regression analyses, we related the memory factor scores to PiB distribution volume ratios (DVR, cerebellar reference) as either a continuous or a dichotomous variable in frontal cortex and a posterior cortical region representing the precuneus, posterior cingulate and lateral parietal cortices (PPCLP), co-varying for age and AMNART IQ (a proxy of cognitive reserve (CR)). A significant inverse relationship for FN-N was found with Aß deposition in frontal (R(2)=0.29, ß=-2.2, p=0.02) and PPCLP cortices (R(2)=0.26, ß=-2.4, p=0.05). In contrast, neither FN-O nor the SRT were significantly related to Aß deposition. Performance on a demanding test of face-name associative memory was related to Aß burden in brain regions associated with memory systems. Associative memory for faces and names, a common complaint among older adults, may be a sensitive marker of early Aß-related impairment.