Piecing it together: atrophy profiles of hippocampal subfields relate to cognitive impairment along the Alzheimer's disease spectrum.

Introduction: People with Alzheimer's disease (AD) experience more rapid declines in their ability to form hippocampal-dependent memories than cognitively normal healthy adults. Degeneration of the whole hippocampal formation has previously been found to covary with declines in learning and memory, but the associations between subfield-specific hippocampal neurodegeneration and cognitive impairments are not well characterized in AD. To improve prognostic procedures, it is critical to establish in which hippocampal subfields atrophy relates to domain-specific cognitive declines among people along the AD spectrum. In this study, we examine high-resolution structural magnetic resonance imaging (MRI) of the medial temporal lobe and extensive neuropsychological data from 29 amyloid-positive people on the AD spectrum and 17 demographically-matched amyloid-negative healthy controls. Methods: Participants completed a battery of neuropsychological exams including select tests of immediate recollection, delayed recollection, and general cognitive status (i.e., performance on the Mini-Mental State Examination [MMSE] and Montreal Cognitive Assessment [MoCA]). Hippocampal subfield volumes (CA1, CA2, CA3, dentate gyrus, and subiculum) were measured using a dedicated MRI slab sequence targeting the medial temporal lobe and used to compute distance metrics to quantify AD spectrum-specific atrophic patterns and their impact on cognitive outcomes. Results: Our results replicate prior studies showing that CA1, dentate gyrus, and subiculum hippocampal subfield volumes were significantly reduced in AD spectrum participants compared to amyloid-negative controls, whereas CA2 and CA3 did not exhibit such patterns of atrophy. Moreover, degeneration of the subiculum along the AD spectrum was linked to a significant decline in general cognitive status measured by the MMSE, while degeneration scores of the CA1 and dentate gyrus were more widely associated with declines on the MMSE and tests of learning and memory. Discussion: These findings provide evidence that subfield-specific patterns of hippocampal degeneration, in combination with cognitive assessments, may constitute a sensitive prognostic approach and could be used to better track disease trajectories among individuals on the AD spectrum.

Elevated CRP and TNF-α levels are associated with blunted neural oscillations serving fluid intelligence.

INTRODUCTION: Inflammatory processes help protect the body from potential threats such as bacterial or viral invasions. However, when such inflammatory processes become chronically engaged, synaptic impairments and neuronal cell death may occur. In particular, persistently high levels of C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-α) have been linked to deficits in cognition and several psychiatric disorders. Higher-order cognitive processes such as fluid intelligence (Gf) are thought to be particularly vulnerable to persistent inflammation. Herein, we investigated the relationship between elevated CRP and TNF-α and the neural oscillatory dynamics serving Gf. METHODS: Seventy adults between the ages of 20-66 years (Mean = 45.17 years, SD = 16.29, 21.4% female) completed an abstract reasoning task that probes Gf during magnetoencephalography (MEG) and provided a blood sample for inflammatory marker analysis. MEG data were imaged in the time-frequency domain, and whole-brain regressions were conducted using each individual's plasma CRP and TNF-α concentrations per oscillatory response, controlling for age, BMI, and education. RESULTS: CRP and TNF-α levels were significantly associated with region-specific neural oscillatory responses. In particular, elevated CRP concentrations were associated with altered gamma activity in the right inferior frontal gyrus and right cerebellum. In contrast, elevated TNF-α levels scaled with alpha/beta oscillations in the left anterior cingulate and left middle temporal, and gamma activity in the left intraparietal sulcus. DISCUSSION: Elevated inflammatory markers such as CRP and TNF-α were associated with aberrant neural oscillations in regions important for Gf. Linking inflammatory markers with regional neural oscillations may hold promise in identifying mechanisms of cognitive and psychiatric disorders.

Movement-related beta and gamma oscillations indicate parallels and disparities between Alzheimer's disease and HIV-associated neurocognitive disorder.

People with HIV (PWH) often develop HIV-related neurological impairments known as HIV-associated neurocognitive disorder (HAND), but cognitive dysfunction in older PWH may also be due to age-related disorders such as Alzheimer's disease (AD). Discerning these two conditions is challenging since the specific neural characteristics are not well understood and limited studies have probed HAND and AD spectrum (ADS) directly. We examined the neural dynamics underlying motor processing during cognitive interference using magnetoencephalography (MEG) in 22 biomarker-confirmed patients on the ADS, 22 older participants diagnosed with HAND, and 30 healthy aging controls. MEG data were transformed into the time-frequency domain to examine movement-related oscillatory activity and the impact of cognitive interference on distinct stages of motor programming. Both cognitively impaired groups (ADS/HAND) performed significantly worse on the task (e.g., less accurate and slower reaction time) and exhibited reductions in frontal and cerebellar beta and parietal gamma activity relative to controls. Disease-specific aberrations were also detected such that those with HAND exhibited weaker gamma interference effects than those on the ADS in frontoparietal and motor areas. Additionally, temporally distinct beta interference effects were identified, with ADS participants exhibiting stronger beta interference activity in the temporal cortex during motor planning, along with weaker beta interference oscillations dispersed across frontoparietal and cerebellar cortices during movement execution relative to those with HAND. These results indicate both overlapping and distinct neurophysiological aberrations in those with ADS disorders or HAND in key motor and top-down cognitive processing regions during cognitive interference and provide new evidence for distinct neuropathology.

Sleep quality differentially modulates neural oscillations and proteinopathy in Alzheimer's disease.

BACKGROUND: Alterations in resting-state neural activity have been reported in people with sleep disruptions and in patients with Alzheimer's disease, but the direct impact of sleep quality on Alzheimer's disease-related neurophysiological aberrations is unclear. METHODS: We collected cross-sectional resting-state magnetoencephalography and extensive neuropsychological and clinical data from 38 biomarker-confirmed patients on the Alzheimer's disease spectrum and 20 cognitively normal older control participants. Sleep efficiency was quantified using the Pittsburgh Sleep Quality Index. FINDINGS: Neural activity in the delta frequency range was differentially affected by poor sleep in patients on the Alzheimer's disease spectrum. Such neural changes were related to processing speed abilities and regional amyloid accumulation, and these associations were mediated and moderated, respectively, by sleep quality. INTERPRETATION: Together, our results point to a mechanistic role for sleep disturbances in the widely reported neurophysiological aberrations seen in patients on the Alzheimer's disease spectrum, with implications for basic research and clinical intervention. FUNDING: National Institutes of Health, USA.

The Impact of the COVID-19 Pandemic on Mental Health and Substance Use among People with and without HIV.

People with HIV (PWH) may be particularly vulnerable to the psychological impacts of COVID-19. To assess this, participants were recruited from two established cohorts of PWH and HIV- adults with the available pre-pandemic baseline data and completed the Beck Depression Inventory-II (BDI-II), Beck Anxiety Inventory (BAI), Alcohol Use Identification Test (AUDIT), National Institute on Drug Abuse Quick Screen (NIDA-QS), and Pittsburgh Sleep Quality Index (PSQI) at two distinct intra-pandemic time periods. All outcomes were evaluated using generalized linear mixed models. In total, 87 participants completed all the questionnaires; 45 were PWH and 42 were HIV-. The pre-pandemic mean BDI-II, BAI, AUDIT and PSQI scores were higher in the PWH cohort. After the onset of the pandemic, the mean BDI-II, AUDIT and PSQI scores increased within the sample as a whole (p < 0.001, p = 0.029 and p = 0.046, respectively). The intra-pandemic mean BDI-II scores fell slightly for both groups and the AUDIT scores increased slightly for the PWH group and fell slightly for the HIV- group, but not significantly. The intra-pandemic PSQI scores increased sharply for both groups. The percentage of PWH and HIV- participants who moved into a more severe category of depression was identical (18%), but more PWH met the criteria for clinical evaluation. The BAI and NIDA-QS scores did not increase significantly. In conclusion, the measures of mental health symptoms and alcohol use increased in both groups after the onset of the pandemic. Although there were no significant differences in the changes between the groups, the PWH had higher baseline scores and the changes in this group had more clinical impacts.

Oscillatory markers of neuroHIV-related cognitive impairment and Alzheimer's disease during attentional interference processing.

People with HIV (PWH) frequently experience mild cognitive decline, which is typically attributed to HIV-associated neurocognitive disorder (HAND). However, such declines could also be a sign of early Alzheimer's disease (AD) in older PWH. Distinguishing these two pathologies in PWH is exceedingly difficult, as there is a major knowledge gap regarding their neural and neuropsychological bases. In the current study, we begin to address this knowledge gap by recording magnetoencephalography (MEG) during a flanker interference task in 31 biomarker-confirmed patients on the AD spectrum (ADS), 25 older participants with HAND, and 31 cognitively-normal controls. MEG data was examined in the time-frequency domain using a data-driven approach. Our results indicated that the clinical groups (ADS/HAND) performed significantly worse than controls on the task and exhibited aberrations in interference-related theta and alpha oscillations, some of which were disease-specific. Specifically, patients (ADS/HAND) exhibited weaker interference activity in frontoparietal and cingulate cortices compared to controls, while the ADS group exhibited stronger theta interference than those with HAND in frontoparietal, occipital, and temporal cortices. These results reveal overlapping and distinct patterns of neurophysiological alterations among those with ADS and HAND in attentional processing centers and suggest the existence of unique oscillatory markers of each condition.

Convergent and divergent oscillatory aberrations during visuospatial processing in HIV-related cognitive impairment and Alzheimer's disease.

Adults with HIV frequently develop a form of mild cognitive impairment known as HIV-associated neurocognitive disorder (HAND), but presumably cognitive decline in older persons with HIV could also be attributable to Alzheimer's disease (AD). However, distinguishing these two conditions in individual patients is exceedingly difficult, as the distinct neural and neuropsychological features are poorly understood and most studies to date have only investigated HAND or AD spectrum (ADS) disorders in isolation. The current study examined the neural dynamics underlying visuospatial processing using magnetoencephalography (MEG) in 31 biomarker-confirmed patients on the ADS, 26 older participants who met criteria for HAND, and 31 older cognitively normal controls. MEG data were examined in the time-frequency domain, and a data-driven approach was utilized to identify the neural dynamics underlying visuospatial processing. Both clinical groups (ADS/HAND) were significantly less accurate than controls on the task and exhibited stronger prefrontal theta oscillations compared to controls. Regarding disease-specific alterations, those with HAND exhibited stronger alpha oscillations than those on the ADS in frontoparietal and temporal cortices. These results indicate both common and unique neurophysiological alterations among those with ADS disorders and HAND in regions serving visuospatial processing and suggest the underlying neuropathological features are at least partially distinct.

Epigenetic aging is associated with aberrant neural oscillatory dynamics serving visuospatial processing in people with HIV.

BACKGROUND: Despite effective antiretroviral therapy, cognitive impairment and other aging-related comorbidities are more prevalent in people with HIV (PWH) than in the general population. Previous research examining DNA methylation has shown PWH exhibit accelerated biological aging. However, it is unclear how accelerated biological aging may affect neural oscillatory activity in virally suppressed PWH, and more broadly how such aberrant neural activity may impact neuropsychological performance. METHODS: In the present study, participants (n = 134) between the ages of 23 - 72 years underwent a neuropsychological assessment, a blood draw to determine biological age via DNA methylation, and a visuospatial processing task during magnetoencephalography (MEG). Our analyses focused on the relationship between biological age and oscillatory theta (4-8 Hz) and alpha (10 - 16 Hz) activity among PWH (n=65) and seronegative controls (n = 69). RESULTS: PWH had significantly elevated biological age when controlling for chronological age relative to controls. Biological age was differentially associated with theta oscillations in the left posterior cingulate cortex (PCC) and with alpha oscillations in the right medial prefrontal cortex (mPFC) among PWH and seronegative controls. Stronger alpha oscillations in the mPFC were associated with lower CD4 nadir and lower current CD4 counts, suggesting such responses were compensatory. Participants who were on combination antiretroviral therapy for longer had weaker theta oscillations in the PCC. CONCLUSIONS: These findings support the concept of interactions between biological aging and HIV status on the neural oscillatory dynamics serving visuospatial processing. Future work should elucidate the long-term trajectory and impact of accelerated aging on neural oscillatory dynamics in PWH.

Regular cannabis use modulates the impact of HIV on the neural dynamics serving cognitive control.

BACKGROUND: Cannabis use and HIV are independently associated with decrements in cognitive control. However, the combined effects of HIV and regular cannabis use on the brain circuitry serving higher-order cognition are unclear. AIMS: Investigate the interaction between cannabis and HIV on neural interference effects during the flanker task and spontaneous activity in regions underlying higher-order cognition. METHODS: The sample consisted of 100 participants, including people with HIV (PWH) who use cannabis, PWH who do not use cannabis, uninfected cannabis users, and uninfected nonusers. Participants underwent an interview regarding their substance use history and completed the Eriksen flanker task during magnetoencephalography (MEG). MEG data were imaged in the time-frequency domain and oscillatory maps depicting the neural flanker interference effect were probed for group differences. Voxel time series were then assessed for group-level differences in spontaneous activity. RESULTS: Group differences in behavioral performance were identified along with group differences in theta and alpha neural interference responses in higher-order regions across the cortex, with nonusers with HIV generally exhibiting the most aberrant responses. Likewise, time series analyses indicated that nonusers with HIV also had significantly elevated spontaneous alpha activity in the left inferior frontal and dorsolateral prefrontal cortices (dlPFC). Finally, we found that spontaneous and oscillatory alpha activity were significantly coupled in the inferior frontal cortex and dlPFC among cannabis users, but not nonusers. CONCLUSIONS: Regular cannabis use appears to suppress the impact of HIV on spontaneous and oscillatory alpha deficits in the left inferior frontal cortex and dlPFC.

Altered visual entrainment in patients with Alzheimer's disease: magnetoencephalography evidence.

Recent research has indicated that rhythmic visual entrainment may be useful in clearing pathological protein deposits in the central nervous system of mouse models of Alzheimer's disease. However, visual entrainment studies in human patients with Alzheimer's disease are rare, and as such the degree to which these patients exhibit aberrations in the neural tracking of rhythmic visual stimuli is unknown. To fill this gap, we recorded magnetoencephalography during a 15 Hz visual entrainment paradigm in amyloid-positive patients on the Alzheimer's disease spectrum and compared their neural responses to a demographically matched group of biomarker-negative healthy controls. Magnetoencephalography data were imaged using a beamformer and virtual sensor data were extracted from the peak visual entrainment responses. Our results indicated that, relative to healthy controls, participants on the Alzheimer's disease spectrum exhibited significantly stronger 15 Hz entrainment in primary visual cortices relative to a pre-stimulus baseline period. However, the two groups exhibited comparable absolute levels of neural entrainment, and higher absolute levels of entertainment predicted greater Mini-mental Status Examination scores, such that those patients whose absolute entrainment amplitude was closer to the level seen in controls had better cognitive function. In addition, 15 Hz periodic activity, but not aperiodic activity, during the pre-stimulus baseline period was significantly decreased in patients on the Alzheimer's disease spectrum. This pattern of results indicates that patients on the Alzheimer's disease spectrum exhibited increased visual entrainment to rhythmic stimuli and that this increase is likely compensatory in nature. More broadly, these results show that visual entrainment is altered in patients with Alzheimer's disease and should be further examined in future studies, as changes in the capacity to entrain visual stimuli may prove useful as a marker of Alzheimer's disease progression.

Signatures of somatosensory cortical dysfunction in Alzheimer's disease and HIV-associated neurocognitive disorder.

Alzheimer's disease is the most common type of dementia in the general population, while HIV-associated neurocognitive disorder is the most common neurological comorbidity in those infected with HIV and affects between 40 and 70% of this population. Both conditions are associated with cognitive impairment and have been associated with aberrant functioning in sensory cortices, but far less is known about their disparate effects on neural activity. Identifying such disparate effects is important because it may provide critical data on the similarities and differences in the neuropathology underlying cognitive decline in each condition. In the current study, we utilized magnetoencephalography, extensive neuropsychological testing and a paired-pulse somatosensory gating paradigm to probe differences in somatosensory processing in participants from two ongoing magnetoencephalography studies. The resulting participant groups included 27 cognitively normal controls, 26 participants with HIV-associated neurocognitive disorder and 21 amyloid biomarker-confirmed patients with Alzheimer's disease. The data were imaged using a beamformer and voxel time series were extracted to identify the oscillatory dynamics serving somatosensory processing, as well as the amplitude of spontaneous cortical activity preceding stimulation onset. Our findings indicated that people with Alzheimer's disease and HIV-associated neurocognitive disorder exhibit normal somatosensory gating but have distinct aberrations in other elements of somatosensory cortical function. Essentially, those with Alzheimer's disease exhibited accentuated neural responses to somatosensory stimulation, along with spontaneous gamma activity preceding stimulus onset. In contrast, those with HIV-associated neurocognitive disorder exhibited normal responses to somatosensory stimulation but had sharply elevated spontaneous gamma activity prior to stimulus onset. These distinct aberrations may reflect the impact of different neuropathological mechanisms underlying each condition. Further, given the differential pattern of deficits in somatosensory cortical function, these measures may function as unique biomarkers in each condition and be useful in identifying persons with HIV who may go on to develop Alzheimer's disease.

Construct validity of the NIH toolbox cognitive domains: A comparison with conventional neuropsychological assessments.

OBJECTIVE: Previous studies have assessed the construct validity of individual subtests in the National Institutes of Health (NIH) Toolbox Cognition Battery (NIHTB-CB), though none have examined the construct validity of the cognitive domains. Importantly, the original NIHTB-CB validation studies were administered on a desktop computer, though the NIHTB-CB is now solely administered via an iPad. We examined the construct validity of each cognitive domain assessed in the NIHTB-CB, including a motor dexterity domain using the iPad application compared to a neuropsychological battery in a sample of healthy adults. METHOD: Eighty-three adults aged 20-66 years (M = 44.35 ± 13.41 years) completed the NIHTB-CB and a comprehensive neuropsychological assessment. Domain scores for each of six cognitive domains (attention and executive function, episodic memory, working memory, processing speed, language, and motor dexterity) and the fluid composite were computed for both batteries. We then assessed the construct validity using Pearson correlations and intraclass correlation coefficients (ICCs) for both demographically corrected and uncorrected domains. RESULTS: We found the attention and executive function, episodic memory, and processing speed domains had poor-to-adequate construct validity (ICCConsistency = -0.029 to 0.517), the working memory and motor dexterity domains and the fluid composite had poor-to-good construct validity (ICCConsistency = 0.215-0.801), and the language domain had adequate-to-good construct validity (ICCConsistency = 0.408-0.829). CONCLUSION: The NIHTB-CB cognitive domains have poor-to-good construct validity, thus researchers should be aware that some tests representing cognitive constructs may not fully reflect the cognitive domain of interest. Future investigation of the construct validity and reliability of the NIHTB-CB administered using the iPad is recommended. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Neuropsychological Outcomes in Adult Patients and Survivors of COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is believed to affect central nervous system functions through various indirect, and possibly direct, mechanisms. We are only now beginning to understand the possible effects of the virus on human cognition. This review summarizes extant yet limited literature on clinical neuropsychological findings in adult coronavirus disease 2019 (COVID-19) patients and survivors. Neuropsychological outcomes were often in the form of cognitive screen results, although various studies administered comprehensive batteries. With respect to screens, the Montreal Cognitive Assessment appeared relatively sensitive to cognitive dysfunction associated with COVID-19. Patients and survivors presented with weaknesses on screens and comprehensive batteries, although the pattern of these weaknesses was not specific to etiology. Broadly, weaknesses were suggestive of executive dysfunction, although more than one study did not detect significant impairment. Weaknesses should be interpreted cautiously due to potential confounds/contributing factors (weaknesses may partly reflect psychiatric sequelae; weaknesses may be over-interpreted due to inadequate assessment of premorbid functioning). Studies reported different approaches in defining impairment, likely contributing to variable findings. The current review discusses ongoing efforts to harmonize approaches to evaluating neuropsychological functioning globally, as well as emphasizes taking a comprehensive approach towards understanding how the disease affects cognition.

Spatially resolved neural slowing predicts impairment and amyloid burden in Alzheimer's disease.

An extensive electrophysiological literature has proposed a pathological 'slowing' of neuronal activity in patients on the Alzheimer's disease spectrum. Supported by numerous studies reporting increases in low-frequency and decreases in high-frequency neural oscillations, this pattern has been suggested as a stable biomarker with potential clinical utility. However, no spatially resolved metric of such slowing exists, stymieing efforts to understand its relation to proteinopathy and clinical outcomes. Further, the assumption that this slowing is occurring in spatially overlapping populations of neurons has not been empirically validated. In the current study, we collected cross-sectional resting state measures of neuronal activity using magnetoencephalography from 38 biomarker-confirmed patients on the Alzheimer's disease spectrum and 20 cognitively normal biomarker-negative older adults. From these data, we compute and validate a new metric of spatially resolved oscillatory deviations from healthy ageing for each patient on the Alzheimer's disease spectrum. Using this Pathological Oscillatory Slowing Index, we show that patients on the Alzheimer's disease spectrum exhibit robust neuronal slowing across a network of temporal, parietal, cerebellar and prefrontal cortices. This slowing effect is shown to be directly relevant to clinical outcomes, as oscillatory slowing in temporal and parietal cortices significantly predicted both general (i.e. Montreal Cognitive Assessment scores) and domain-specific (i.e. attention, language and processing speed) cognitive function. Further, regional amyloid-ß accumulation, as measured by quantitative 18F florbetapir PET, robustly predicted the magnitude of this pathological neural slowing effect, and the strength of this relationship between amyloid-ß burden and neural slowing also predicted attentional impairments across patients. These findings provide empirical support for a spatially overlapping effect of oscillatory neural slowing in biomarker-confirmed patients on the Alzheimer's disease spectrum, and link this effect to both regional proteinopathy and cognitive outcomes in a spatially resolved manner. The Pathological Oscillatory Slowing Index also represents a novel metric that is of potentially high utility across a number of clinical neuroimaging applications, as oscillatory slowing has also been extensively documented in other patient populations, most notably Parkinson's disease, with divergent spectral and spatial features.

The 3-Item "Apathy" Subscale Within the GDS-15 Is Not Supported in De Novo Parkinson's Disease Patients: Analysis of the PPMI Cohort.

This study examined individual components of the Geriatric Depression Scale-15 (GDS-15) to determine whether the 3-item Withdrawal-Apathy-Lack of Vigor (WAV) subscale, which has been validated in older adults and advanced Parkinson's disease (PD), was applicable to newly diagnosed patients with PD. Baseline Parkinson's Progression Markers Initiative (PPMI) data (n = 345), including GDS-15 and Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) depression, apathy, and anxiety scores, were examined. Data reduction techniques (i.e., principal components, confirmatory factor analyses) were used. Model fit was poor for the previously identified GDS-15 factor structures. Via principal components analysis, 5 components were identified, none of which reflected the 3-item WAV subscale previously reported in the literature. Internal consistency of the GDS-15 was acceptable, as was the internal consistency for the largest component (labeled "Dysphoria"). All 5 components significantly correlated with the MDS-UPDRS depression, apathy, and anxiety items. Model fit was fair for the "Dysphoria" factor only. Overall, the 3-item WAV factor reported in previous literature was not supported in this sample of de novo PD patients.

Apathy as a Within-Person Mediator of Depressive Symptoms and Cognition in Parkinson's Disease: Longitudinal Mediation Analyses.

OBJECTIVE: Greater depressive symptoms are associated with worse cognitive functions in Parkinson's disease (PD); however, it is unclear what underlying factors drive this association. Apathy commonly develops in PD and may be a pathway through which depressive symptoms negatively influence cognition. Prior research examining depressive symptoms, apathy, and cognition in PD is limited by being predominantly cross-sectional. This study examined the role of apathy as a within- and between-person mediator for the longitudinal relationships between depression severity and cognitive functioning in patients with early PD. METHODS: Participants included 487 individuals newly diagnosed with PD followed annually for up to 5 years by the Parkinson's Progression Marker Initiative. At each visit, participants completed depressive symptom measures, apathy ratings, and cognitive tests. Multi-level structural equation models examined both the within- and between-person effects of depressive symptoms on cognition through apathy, controlling for demographics and motor severity. RESULTS: At the within-person level, apathy mediated the association between depressive symptoms and select cognitive functions (global cognition, attention/working memory, visuospatial functions, and immediate verbal memory; indirect effects, bootstrap p's <0.05). Significant between-person direct effects were found for depressive symptoms predicting apathy (boostrap p <0.001) and lower scores on most cognitive tests (bootstrap p's <0.05). However, the indirect effects did not reach significance, suggesting between-person mediation did not occur. CONCLUSION: Findings suggest worsening of depressive symptoms over time in patients with PD may be a risk factor for increased apathy and subsequent decline in specific cognitive functions.

Somatosensory dysfunction is masked by variable cognitive deficits across patients on the Alzheimer's disease spectrum.

BACKGROUND: Alzheimer's disease (AD) is generally thought to spare primary sensory function; however, such interpretations have drawn from a literature that has rarely taken into account the variable cognitive declines seen in patients with AD. As these cognitive domains are now known to modulate cortical somatosensory processing, it remains possible that abnormalities in somatosensory function in patients with AD have been suppressed by neuropsychological variability in previous research. METHODS: In this study, we combine magnetoencephalographic (MEG) brain imaging during a paired-pulse somatosensory gating task with an extensive battery of neuropsychological tests to investigate the influence of cognitive variability on estimated differences in somatosensory function between biomarker-confirmed patients on the AD spectrum and cognitively-normal older adults. FINDINGS: We show that patients on the AD spectrum exhibit largely non-significant differences in somatosensory function when cognitive variability is not considered (p-value range: .020-.842). However, once attention and processing speed abilities are considered, robust differences in gamma-frequency somatosensory response amplitude (p < .001) and gating (p = .004) emerge, accompanied by significant statistical suppression effects. INTERPRETATION: These findings suggest that patients with AD exhibit insults to functional somatosensory processing in primary sensory cortices, but these effects are masked by variability in cognitive decline across individuals. FUNDING: National Institutes of Health, USA; Fremont Area Alzheimer's Fund, USA.

Psychometric properties of the Montreal Cognitive Assessment (MoCA) in inpatient liver transplant candidates.

Hepatic encephalopathy (HE) is a consequence of liver disease and often diagnosed via psychometric testing. With inpatients, the Montreal Cognitive Assessment (MoCA) may be used as part of cognitive screening for transplant candidacy. However, the MoCA was developed to detect mild cognitive impairment in aging populations and its psychometric properties in inpatients with liver disease have not been determined. Retrospective chart review identified inpatient liver transplant candidates who were administered a MoCA as part of their neuropsychological screening and had either no cognitive dysfunction or a diagnosis of HE made by a neuropsychologist (n = 57, mean age = 48.8 ± 12.6 years). Psychometric analyses were conducted and regression analysis was performed to determine the predictive value of different variables on total MoCA scores. Internal consistency of MoCA domain scores was good (α = 0.80). Significant inverse relationships were found with Trail Making Test, Parts A and B (r's = -0.43 and -0.71, respectively). A cutoff score of 24 or below had the best sensitivity (0.72) and specificity (0.77) for identifying those with a diagnosis of HE. Increasing age and the presence of altered mental status were the strongest predictors of lower MoCA scores (both p's < 0.05, ηp2 = 0.10-0.14). The MoCA is appropriate to use with inpatient liver transplant candidates, with a cutoff of 24 or below to detect abnormal cognition. In addition to the clinical interview and other neuropsychological tests (including, but not limited to, the Trail Making Test, Parts A and B), low MoCA scores can help determine the presence of HE.

Stress-induced aberrations in sensory processing predict worse cognitive outcomes in healthy aging adults.

It is well recognized that not all individuals age equivalently, with functional dependence attributable, at least in part, to stress accumulated across the lifespan. Amongst these dependencies are age-related declines in cognitive function, which may be the result of impaired inhibitory processing (e.g., sensory gating). Herein, we examined the unique roles of life and biological stress on somatosensory gating dynamics in 74 adults (22-72 years old). Participants completed a sensory gating paired-pulse electrical stimulation paradigm of the right median nerve during magnetoencephalography (MEG) and data were subjected to advanced oscillatory and time-domain analysis methods. We observed separable mechanisms by which increasing levels of life and biological stress predicted higher oscillatory gating ratios, indicative of age-related impairments in inhibitory function. Specifically, elevations in life stress significantly modulated the neural response to the first stimulation in the pair, while elevations in biological stress significantly modulated the neural response to the second stimulation in the pair. In contrast, neither elevations in life nor biological stress significantly predicted the gating of time-domain neural activity in the somatosensory cortex. Finally, our study is the first to link stress-induced decline in sensory gating to cognitive dysfunction, suggesting that gating paradigms may hold promise for detecting discrepant functional trajectories in age-related pathologies in the future.

Gray matter volumes discriminate cognitively impaired and unimpaired people with HIV.

BACKGROUND: Current diagnostic criteria of HIV-associated neurocognitive disorders (HAND) rely on neuropsychological assessments. The aim of this study was to evaluate if gray matter volumes (GMV) can distinguish people with HAND, neurocognitively unimpaired people with HIV (unimpaired PWH), and uninfected controls using linear discriminant analyses. METHODS: A total of 231 participants, including 110 PWH and 121 uninfected controls, completed a neuropsychological assessment and an MRI protocol. Among PWH, HAND (n = 48) and unimpaired PWH (n = 62) designations were determined using the widely accepted Frascati criteria. We then assessed the extent to which GMV, corrected for intracranial volume, could accurately distinguish the three groups using linear discriminant analysis. Sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, area under the curve (AUC), and accuracy were computed for each model using the classification results based on GMV compared to the neuropsychological assessment. RESULTS: The best performing model was comprised of bilaterally combined GMV and was stratified by sex. Among males, sensitivity was 85.2% (95% CI: 66.3%-95.8%), specificity was 97.0% (95% CI: 91.6%-99.4%), and the AUC was 0.91 (95% CI: 0.83-0.99). Among females, sensitivity was 100.0% (95% CI: 83.9%-100.0%), specificity was 98.8% (95% CI: 93.4%-100.0%), and the AUC was 0.99 (95% CI: 0.98-1.00). CONCLUSIONS: GMV accurately discriminated HAND from unimpaired PWH and controls. Measures of GMV may be highly sensitive to HAND, and revisions to the Frascati criteria should consider including GMV in conjunction with a neuropsychological assessment to diagnose HAND.