Changes in Anticholinergic Burden in Parkinson's Disease After Deep Brain Stimulation.

OBJECTIVE: This study aimed to evaluate the effect of deep brain stimulation (DBS) on anticholinergic burden in Parkinson's disease (PD) and the association of anticholinergic burden with cognition. MATERIALS AND METHODS: A retrospective chart review in patients with PD who underwent bilateral subthalamic nucleus (STN) or globus pallidus internus (GPi) DBS from 2010 to 2020 reviewed medications with anticholinergic burden at baseline, six months, and one year (N = 216) after surgery. The cumulative anticholinergic burden at each visit was calculated using the Anticholinergic Risk Scale (ARS). RESULTS: ARS scores were significantly lower for patients six months and one year after surgery than at baseline (z = 6.58, p < 0.0001; z = 6.99, p < 0.0001). Change in ARS scores at both six months and one year were driven by down-titration of PD medications (z = 9.35, p < 0.0001; z = 8.61, p < 0.0001), rather than changes in pain, psychiatric, or urinary medications with anticholinergic effects. There was no significant difference in change in ARS scores at one year between targets (t = 0.41, p = 0.68). In addition, there was no significant association between anticholinergic burden and cognitive performance. CONCLUSION: GPi and STN DBS are associated with decreased anticholinergic burden due to PD medications in the first year after surgery.

Correlating continuously captured home-based digital biomarkers of daily function with postmortem neurodegenerative neuropathology.

BACKGROUND: Outcome measures available for use in Alzheimer's disease (AD) clinical trials are limited in ability to detect gradual changes. Measures of everyday function and cognition assessed unobtrusively at home using embedded sensing and computing generated "digital biomarkers" (DBs) have been shown to be ecologically valid and to improve efficiency of clinical trials. However, DBs have not been assessed for their relationship to AD neuropathology. OBJECTIVES: The goal of the current study is to perform an exploratory examination of possible associations between DBs and AD neuropathology in an initially cognitively intact community-based cohort. METHODS: Participants included in this study were ≥65 years of age, living independently, of average health for age, and followed until death. Algorithms, run on the continuously-collected passive sensor data, generated daily metrics for each DB: cognitive function, mobility, socialization, and sleep. Fixed postmortem brains were evaluated for neurofibrillary tangles (NFTs) and neuritic plaque (NP) pathology and staged by Braak and CERAD systems in the context of the "ABC" assessment of AD-associated changes. RESULTS: The analysis included a total of 41 participants (M±SD age at death = 92.2±5.1 years). The four DBs showed consistent patterns relative to both Braak stage and NP score severity. Greater NP severity was correlated with the DB composite and reduced walking speed. Braak stage was associated with reduced computer use time and increased total time in bed. DISCUSSION: This study provides the first data showing correlations between DBs and neuropathological markers in an aging cohort. The findings suggest continuous, home-based DBs may hold potential to serve as behavioral proxies that index neurodegenerative processes.

Neurocognitive markers of passive suicidal ideation in late-life depression.

OBJECTIVES: (1) To delineate whether cognitive flexibility and inhibitory ability are neurocognitive markers of passive suicidal ideation (PSI), an early stage of suicide risk in depression and (2) to determine whether PSI is associated with volumetric differences in regions of the prefrontal cortex (PFC) in middle-aged and older adults with depression. DESIGN: Cross-sectional study. SETTING: University medical school. PARTICIPANTS: Forty community-dwelling middle-aged and older adults with depression from a larger study of depression and anxiety (NIMH R01 MH091342-05 PI: O'Hara). MEASUREMENTS: Psychiatric measures were assessed for the presence of a DSM-5 depressive disorder and PSI. A neurocognitive battery assessed cognitive flexibility, inhibitory ability, as well as other neurocognitive domains. RESULTS: The PSI group (n = 18) performed significantly worse on cognitive flexibility and inhibitory ability, but not on other neurocognitive tasks, compared to the group without PSI (n = 22). The group with PSI had larger left mid-frontal gyri (MFG) than the no-PSI group. There was no association between cognitive flexibility/inhibitory ability and left MFG volume. CONCLUSIONS: Findings implicate a neurocognitive signature of PSI: poorer cognitive flexibility and poor inhibitory ability not better accounted for by other domains of cognitive dysfunction and not associated with volumetric differences in the left MFG. This suggests that there are two specific but independent risk factors of PSI in middle- and older-aged adults.

Mood and activity changes during the COVID-19 pandemic in rural and urban Veterans and their cohabitants.

OBJECTIVES: We aimed to examine the impact of COVID-19 pandemic-related stay-at-home orders on weekly reports of mood and activity before and during COVID-19 in a sample of older Veterans and their cohabitants. METHODS: Urban and rural Veterans and their cohabitants living in the Pacific Northwest ≥62 years old were enrolled as part of the Collaborative Aging Research Using Technology initiative (n = 100, age = 71.2 ± 6.5, 41% women). Participants reported frequency of social activities (e.g., travel away), physical illness, and mood (blue mood and loneliness) via weekly online health forms. RESULTS: A total of 2,441 weekly online health forms (OHFs) were collected from 100 participants. During the COVID-19 pandemic, blue mood (OR = 4.4, p < .0001) and loneliness (OR = 7.2, p < .0001) were significantly higher than before the pandemic, and travel away from home was significantly lower (OR = 0.5, p < .0001). Prevalence of blue mood and loneliness were not associated with rurality. CONCLUSIONS: The current study established that blue mood and loneliness were significantly more prevalent in older Veterans following COVID-19 stay-at-home orders regardless of rurality. CLINICAL IMPLICATIONS: The COVID-19 pandemic associated health precautions, while necessary to curb acute health risks, have created a unique situation that places vulnerable populations at increased risk of low mood.

Insights about personality traits and cognitive performance and decline in adults 51-59 Years old from the Wisconsin longitudinal study.

OBJECTIVES: To delineate midlife personality dimensions of early cognitive change in an age-homogenous sample of U.S. older adults. DESIGN: Longitudinal study of 6133 adults from the Wisconsin Longitudinal Study (WLS). MEASURES: Middle-aged participants (mean age = 53.2; SD = 0.6) from the WLS completed the 'Big-5' personality assessment in 1992. Mixed effects models examined whether midlife personality traits were associated with change in cognitive performance from participant's mid-60s (2004-2005) to early 70s (2011). The cognitive battery assessed abstract reasoning (AR), category fluency (CF), working memory (WM), and delayed verbal memory (DVM). Models adjusted for sex, education, and subjective health. RESULTS: High Openness was a significant predictor of change in AR, CF, and DVM. These cognitive outcomes declined less among those with high Openness, but the effect sizes for Openness by time were small (R2 s < 0.01). AR and CF were characterized by higher overall performance with high Openness, but with relatively parallel change for the highest and lowest Openness quartiles. There was no advantage of Openness to DVM by the second assessment. High Conscientiousness was a predictor of more change for DVM, though the effect size was small (R 2  < 0.01). CONCLUSIONS: None of the midlife personality traits were uniformly associated with change in cognitive performance in early older adulthood. High midlife Openness had the most noteworthy impact on cognition. Interventions designed to target Openness have potential to elevate and maintain a higher threshold of performance in some cognitive domains, but may only have a small impact on cognitive change.

Preparing the Next Generation of Academic Researchers During the Pandemic: Lessons from a National Mental Health Research Postdoctoral Fellowship.

OBJECTIVE: The COVID-19 pandemic has severely disrupted all aspects of academic medicine, including post-doctoral research fellowship training. The current survey examined ways in which research fellows across 28 U.S. nationally diverse sites have been impacted. METHODS: Survey participants included 62 M.D. and Ph.D. post-doctoral fellows and 27 local fellowship center directors within the Veterans Affairs (VA) Advanced Fellowship in Mental Illness Research and Treatment (MIRT), a national fellowship program tasked to develop academic clinician researchers within the field of mental health. Survey questions focused on productivity and challenges experienced by fellows during the pandemic. RESULTS: Half of fellows reported working entirely off-site during the COVID-19 pandemic. All fellows reported some level of disruption in productivity during the pandemic; 73% reported a disruption in data collection, 69% reported decreased scholarly output, 41% reported disruption in grant writing, and 73% reported disruption in ability to provide clinical care. Yet, the majority of fellows (66%) reported not having to change their research goals, pivoting to telehealth-based data collection, and employing extant data for research projects and peer-reviewed publications. CONCLUSIONS: The results of the fellow and director surveys highlight the associated disruption of the COVID-19 pandemic on fellowship-related activities and parallel ingenuity of programs to continue conducting research and clinical services in a modified fashion. While many research goals continued unabated, the findings suggest alterations in data collection methodology and a focus on using extant data, which may have a residual influence on future early career research grant applications.

Cognition during active methamphetamine use versus remission.

OBJECTIVE: To evaluate whether cognitive performance in adults with active methamphetamine use (MA-ACT) differs from cognitive performance in adults in remission from MA use disorder (MA-REM) and adults without a history of substance use disorder (CTLs). METHOD: MA-ACT (n = 36), MA-REM (n = 48), and CTLs (n = 62) completed the Neuropsychological Assessment Battery (NAB). RESULTS: The MA-ACT group did not perform significantly worse than CTLs on any NAB Index. The MA-REM group performed significantly (p < 0.050) worse than CTLs on the NAB Memory Index. The MA-ACT group performed significantly better than CTLs and the MA-REM group on the Executive Functions Index. CONCLUSIONS: Some cognitive deficits are apparent during remission from MA use, but not during active use; this may result in clinical challenges for adults attempting to maintain recovery and continue with treatment.

Depression, health comorbidities, cognitive symptoms and their functional impact: Not just a geriatric problem.

OBJECTIVE: To compare the prevalence of cognitive symptoms and their functional impact by age group accounting for depression and number of other health conditions. METHODS: We analyzed data from the 2011 Behavioral Risk Factor Surveillance System, a population-based, cross-sectional telephone survey of US adults. Twenty-one US states asked participants (n = 131, 273) about cognitive symptoms (worsening confusion or memory loss in the past year) and their functional impact (interference with activities and need for assistance). We analyzed the association between age, depression history and cognitive symptoms and their functional impact using logistic regression and adjusted for demographic characteristics and other health condition count. RESULTS: There was a significant interaction between age and depression (p < 0.0001). In adults reporting depression, the adjusted odds of cognitive symptoms in younger age groups (<75 years) were comparable or greater to those in the oldest age group (≥75 years) with a peak in the middle age (45-54 years) group (OR 1.9 (95% Confidence Interval: 1.4-2.5). In adults without depression, adults <75 years had a significantly lower adjusted odds of cognitive symptoms compared to the oldest age group with the exception of the middle-aged group where the difference was not statistically significant. Over half of adults under age 65 with depression reported that cognitive symptoms interfered with life activities compared to 35.7% of adults ≥65 years. CONCLUSIONS: Cognitive symptoms are not universally higher in older adults; middle-aged adults are also particularly vulnerable. Given the adverse functional impact associated with cognitive symptoms in younger adults, clinicians should assess cognitive symptoms and their functional impact in adults of all ages and consider treatments that impact both cognition and functional domains.

Posttraumatic Stress Disorder-Associated Cognitive Deficits on the Repeatable Battery for the Assessment of Neuropsychological Status in a Veteran Population.

BACKGROUND: Posttraumatic stress disorder (PTSD) is a frequent problem of veterans receiving care and is often associated with cognitive deficits. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) is a well-validated cognitive screening measure often used in the US Department of Veterans Affairs (VA), particularly in neurorehabilitation settings. However, the influence of PTSD on RBANS performance is unclear, particularly within a heterogeneous VA outpatient population in which PTSD and traumatic brain injury (TBI) may not be the primary focus of care. METHODS: Participants included 153 veterans with complex deployment-related health problems, including a diagnosis of PTSD (n = 98) and a history of TBI (n = 92). All veterans completed a targeted cognitive battery that included the Wechsler Test of Adult Reading, the Wechsler Adults Intelligence Scale, measure assessing processing speed, attention, and cognitive flexibility, and RBANS. RESULTS: A diagnosis of PTSD was associated with worse performance on the Story Recall subtest of the RBANS, but not on any other cognitive measures. A diagnosis of mild TBI, or co-occurring PTSD and TBI did not predict cognitive performance on any measures. CONCLUSIONS: The RBANS best captured cognitive deficits associated with PTSD compared with a history of mild TBI or co-occurring mild TBI and PTSD. These findings may provide insight into the interpretation and attribution of cognitive deficits in the veteran population.

Patient Satisfaction With Geriatric Psychiatry Services via Video Teleconference.

OBJECTIVE: The objective for the current study is to examine patient satisfaction with geropsychiatry services provided via video telehealth. METHODS: Participants included community-dwelling older Veterans receiving geriatric psychiatry services via telehealth across regions of the Pacific Northwest and Southwestern United States. Participants completed a paper-based survey examining satisfaction with services following the completion of two medication management visits with a geropsychiatrist. RESULTS: The majority of participants (90%) reported liking or even preferring geriatric telepsychiatry, despite the experience being novel for the majority of patients. Eighty-three percent of participants reported that receiving telegeropsychiatry services was the same (n = 30) or better (n = 3) than being seen in-person. Participants saved an average of 168 driving miles (means and standard deviations = 59.2; range 2-480) each visit. CONCLUSION: The findings of the current study suggest that older adults accept and are broadly satisfied with telegeropsychiatry services. This modality of care increased access to specialty care and decreased travel hardship.

Subjective but Not Objective Sleep is Associated with Subsyndromal Anxiety and Depression in Community-Dwelling Older Adults.

OBJECTIVE: To examine the relationship between subclinical anxiety and depressive symptoms and objective sleep architecture measures and subjective sleep reports in older adults. METHODS: Community-dwelling older adults (N = 167) self-rated their current severity of anxiety symptoms, depressive symptoms, daytime sleepiness, and global sleep quality. Participants received overnight ambulatory polysomnography to assess sleep architecture. Multivariate linear regression models examined associations between anxiety and depressive symptoms and objective and subjective sleep measures. RESULTS: Significant findings emerged for subjective sleep, with higher depression and anxiety scores associated with worse global sleep quality and greater anxiety scores associated with greater daytime sleepiness. No significant associations were observed between subclinical levels of anxiety or depressive symptoms with sleep architecture. CONCLUSION: Subclinical levels of late-life anxiety and depression have distinct associations with subjective sleep disturbance. Findings implicate subjective measures of sleep quality and daytime sleepiness as stronger trait markers for subthreshold psychiatric symptoms than objective sleep biomarkers.

Unlocking Neurocognitive Substrates of Late-Life Affective Symptoms Using the Research Domain Criteria: Worry Is an Essential Dimension.

While investigations have sought to identify the distinct and shared contributions of anxiety and depression to neurocognitive processes in late life, less is known regarding the further contribution of worry, a unique and critical dimension of affective dysregulation. Capturing the full range of symptoms, as inspired by the NIH Research Domain Criteria (RDoC), may provide finer-grained information on inter-relationships among worry, anxiety and depression on neurocognitive processing in later life. The objective of this study was to determine if the dimensional trait of worry intensifies known negative associations of dimensional measures of anxiety and depressive symptoms with neurocognitive processes, specifically cognitive control and memory processes. Using a cross-sectional and observational design, this study was conducted within a translational research center located with a Veterans medical center in Northern California. One hundred and nineteen community-residing older adults ages 65-91 years participated, and were characterized with psychiatric and neurocognitive dimensional measures. Affective symptom severity was assessed with the Penn State Worry Questionnaire, the Beck Anxiety Inventory (BAI), and the Beck Depression Inventory-II. Primary neurocognitive outcomes were inhibitory control assessed using a Stroop paradigm and delayed verbal memory assessed with the Rey Auditory Verbal Learning Test. Secondary outcomes included other less frequently examined cognitive control mechanisms (working memory, information processing, and verbal fluency) and memory processes (visual delayed memory). Contrary to prediction, the dimensional trait of worry attenuated negative associations between anxiety and depressive symptoms and inhibitory control on the one hand, and between depressive symptoms and delayed verbal memory processes on the other. In the secondary models, symptom dimensions were not associated with other cognitive control or visual delayed memory processes. Our fine-grained approach, in line with the NIMH RDoC model, suggests the neurocognitive processes associated with dimensional measures of late-life affective symptoms are dissociable. Specifically, dimensional measures of worry operate independently from other anxiety and depression symptoms to reveal differential patterns of neurocognitive processes associated with affective dysregulation.

Altered Microstructural Caudate Integrity in Posttraumatic Stress Disorder but Not Traumatic Brain Injury.

OBJECTIVE: Given the high prevalence and comorbidity of combat-related PTSD and TBI in Veterans, it is often difficult to disentangle the contributions of each disorder. Examining these pathologies separately may help to understand the neurobiological basis of memory impairment in PTSD and TBI independently of each other. Thus, we investigated whether a) PTSD and TBI are characterized by subcortical structural abnormalities by examining diffusion tensor imaging (DTI) metrics and volume and b) if these abnormalities were specific to PTSD versus TBI. METHOD: We investigated whether individuals with PTSD or TBI display subcortical structural abnormalities in memory regions by examining DTI metrics and volume of the hippocampus and caudate in three groups of Veterans: Veterans with PTSD, Veterans with TBI, and Veterans with neither PTSD nor TBI (Veteran controls). RESULTS: While our results demonstrated no macrostructural differences among the groups in these regions, there were significant alterations in microstructural DTI indices in the caudate for the PTSD group but not the TBI group compared to Veteran controls. CONCLUSIONS: The result of increased mean, radial, and axial diffusivity, and decreased fractional anisotropy in the caudate in absence of significant volume atrophy in the PTSD group suggests the presence of subtle abnormalities evident only at a microstructural level. The caudate is thought to play a role in the physiopathology of PTSD, and the habit-like behavioral features of the disorder could be due to striatal-dependent habit learning mechanisms. Thus, DTI appears to be a vital tool to investigate subcortical pathology, greatly enhancing the ability to detect subtle brain changes in complex disorders.

Disentangling cognition and emotion in older adults: the role of cognitive control and mental health in emotional conflict adaptation.

OBJECTIVE: Recent research suggests cognition has a bidirectional relationship with emotional processing in older adults, yet the relationship is still poorly understood. We aimed to examine a potential relationship between late-life cognitive function, mental health symptoms, and emotional conflict adaptation. We hypothesized that worse cognitive control abilities would be associated with poorer emotional conflict adaptation. We further hypothesized that a higher severity of mental health symptoms would be associated with poorer emotional conflict adaptation. METHODS: Participants included 83 cognitively normal community-dwelling older adults who completed a targeted mental health and cognitive battery, and emotion and gender conflict-adaptation tasks. RESULTS: Consistent with our hypothesis, poorer performance on components of cognitive control, specifically attention and working memory, was associated with poorer emotional conflict adaptation. This association with attention and working memory was not observed in the non-affective-based gender conflict adaptation task. Mental health symptoms did not predict emotional conflict adaptation, nor did performance on other cognitive measures. CONCLUSION: Our findings suggest that emotion conflict adaptation is disrupted in older individuals who have poorer attention and working memory. Components of cognitive control may therefore be an important potential source of inter-individual differences in late-life emotion regulation and cognitive affective deficits. Copyright © 2016 John Wiley & Sons, Ltd.

Longitudinal association of delta activity at sleep onset with cognitive and affective function in community-dwelling older adults.

OBJECTIVE: This investigation sought to determine whether delta activity at sleep onset (DASO) in the sleep electroencephalography of older adults represents normal variation or is associated with clinical pathology. To this end, we examined its longitudinal associations with cognitive and affective function in older adults without dementia. METHODS: Participants were 153 community-dwelling older adults without dementia. We evaluated polysomnography (PSG), cognitive performance, and affective function at four time points: baseline, 12, 24, and 36 months. All participants completed PSG and measures of global cognition, delayed verbal memory, information processing speed, attention, inhibition, verbal naming, visuospatial ability, and measures of anxiety and depression. DASO was defined as sequences of rhythmic anterior delta activity on PSG in the transition from awake to sleep during the baseline assessment (Figure ). RESULTS: At the baseline, 83 women and 70 men, mean age 71.3 ± 0.6 years participated and 19.6% of participants exhibited DASO. Age, years of education, gender, and body mass index did not differ according to DASO status. Linear mixed modeling showed that the presence of DASO was actually associated with lower levels of anxiety and depression. Further, participants with DASO, versus those without DASO, exhibited a trend towards better cognitive performance over time, although none of these associations reached statistical significance. CONCLUSIONS: Whereas DASO was associated with better affective function, no significant association was found between DASO and cognitive change over time. These longitudinal findings support the view that the presence of DASO in healthy older adults represents normal variation rather than pathological aging. Copyright © 2016 John Wiley & Sons, Ltd.

Delta Activity at Sleep Onset and Cognitive Performance in Community-Dwelling Older Adults.

STUDY OBJECTIVES: Frontal intermittent rhythmic delta activity (FIRDA) has long been considered to be an abnormal variant in the electroencephalogram (EEG) among older adults. Prior work also indicates a predominance of slow wave EEG activity among patients with dementia. However, instability of state control occurring with aging generally and among many neurodegenerative diseases raises the possibility that FIRDA might represent the intrusion of sleep related elements of the EEG into the waking state. We examined delta activity at sleep onset (DASO) in community-dwelling, older adults without dementia, and examined whether this activity is related to poorer cognitive performance. METHODS: 153 community-dwelling, older adults without dementia underwent overnight polysomnography and measures of global cognition, delayed verbal memory, information processing speed, attention, inhibition, verbal naming, and visuospatial ability. Delta activity during sleep/wake transitions (scored either as Waking or N1) was analyzed visually. RESULTS: Participants were 83 women and 70 men, mean age 71.3 ± 0.6 y. DASO was present in 30 participants (19.6%). Age, years of education, sex, and body mass index did not differ between DASO (+) and (-) groups. Multiple regression analyses indicated faster reading of the Stroop color words in DASO (+) subjects (P = 0.007). None of the other cognitive domains differed between the two groups. CONCLUSIONS: DASO was relatively common in our sample of community-dwelling, older adults without dementia. DASO was not associated with poorer performance on any cognitive domain. Instead, individuals with DASO demonstrated better performance on a simple reading task. Although these findings suggest that an abnormal EEG activity may represent normal variation, our work underscores the importance of distinguishing DASO from FIRDA when examining sleep in older adults. COMMENTARY: A commentary on this article appears in this issue on page 725.

Performance variability during a multitrial list-learning task as a predictor of future cognitive decline in healthy elders.

INTRODUCTION: In clinical settings, neuropsychological test performance is traditionally evaluated with total summary scores (TSS). However, recent studies demonstrated that indices of intraindividual variability (IIV) yielded unique information complementing TSS. This 18-month longitudinal study sought to determine whether IIV indices derived from a multitrial list-learning test (the Rey Auditory Verbal Learning Test) provided incremental utility in predicting cognitive decline in older adults compared to TSS. METHOD: Ninety-nine cognitively intact older adults (aged 65 to 89 years) underwent neuropsychological testing (including the Rey Auditory Verbal Learning Test) at baseline and 18-month follow-up. Participants were classified as cognitively stable (n = 65) or declining (n = 34) based on changes in their neuropsychological test performance. Logistic regression modeling tested the ability of baseline TSS indices (sum of Trials 1-5, immediate recall, and delayed recall) and IIV indices (lost access and gained access) to discriminate between stable and declining individuals. RESULTS: Higher values of both lost access and gained access at baseline were associated with an increased risk for decline at 18-month follow-up. Further, the IIV indices provided predictive utility above and beyond the TSS indices. CONCLUSION: These results highlight the value of analyzing IIV in addition to TSS during neuropsychological evaluation in older adults. High levels of IIV may reflect impairment in anterograde memory systems and/or executive dysfunction that may serve as a prognostic indicator of cognitive decline.