Cognition-oriented treatments and physical exercise on cognitive function in Huntington's disease: a systematic review.

Cognitive impairment is prevalent in Huntington's disease (HD), with no treatments currently available. While cognition-oriented treatments and physical exercise have shown efficacy in improving cognition in other populations, they have not been systematically reviewed in HD. This systematic review aims to examine the effects of cognitive and exercise interventions on cognition in HD, along with effects on psychosocial function, functional independence, and neuroimaging outcomes. Seventeen studies (three cognitive, seven exercise, seven combining cognitive and physical exercise) were included. While there was generally low certainty of evidence, interventions that included cognitive training appeared to have larger effect sizes on cognition, while physical exercise (alone or combined with cognitive rehabilitation or stimulation) showed negligible effect sizes. On the other hand, combined interventions had larger effects on psychosocial function. Finally, effects on functional independence appeared negligible following exercise and combined interventions, and effects on neuroimaging outcomes were inconclusive. Larger studies should seek to confirm the benefits of cognitive and physical interventions, and further explore changes in functional independence and neural outcomes.

Distribution Patterns of Astrocyte Populations in the Human Cortex.

Astrocytes are a major class of glial cell in the central nervous system that have a diverse range of types and functions thought to be based on their anatomical location, morphology and cellular properties. Recent studies highlight that astrocyte dysfunction contributes to the pathogenesis of neurological conditions. However, few studies have described the pattern, distribution and density of astrocytes in the adult human cortex. This study mapped the distribution and density of astrocytes immunolabelled with a range of cytoskeletal and membrane markers in the human frontal cortex. Distinct and overlapping astrocyte populations were determined. The frontal cortex from ten normal control cases (75 ± 9 years) was immunostained with glial fibrillary acidic protein (GFAP), aldehyde dehydrogenase-1 L1 (ALDH1L1), connexin-43 (Cx43), aquaporin-4 (AQP4), and glutamate transporter 1 (GLT-1). All markers labelled populations of astrocytes in the grey and white matter, separate cortical layers, subpial and perivascular regions. All markers were informative for labelling different cellular properties and cellular compartments of astrocytes. ALDH1L1 labelled the largest population of astrocytes, and Cx43-immunopositive astrocytes were found in all cortical layers. AQP4 and GLT-1 labelled distal astrocytic process and end-feet in the same population of astrocytes (98% of GLT-1-immunopositive astrocytes contained AQP4). In contrast, GFAP, the most widely used marker, predominantly labelled astrocytes in superficial cortical layers. This study highlights the diversity of astrocytes in the human cortex, providing a reference map of the distribution of distinct and overlapping astrocyte populations which can be used for comparative purposes in various disease, inflammatory and injury states involving astrocytes.

Social Cognition and Social Functioning in MCI and Dementia in an Epidemiological Sample.

OBJECTIVE: Social cognition is impaired in mild cognitive impairment (MCI) and dementia. However, its relationship to social functioning and perceived social support has yet to be explored. Here, we examine how theory of mind (ToM) relates to social functioning in MCI and dementia. METHODS: Older adults (cognitively normal = 1272; MCI = 132; dementia = 23) from the PATH Through Life project, a longitudinal, population-based study, were assessed on the Reading the Mind in the Eyes Test (RMET), measures of social functioning, and social well-being. The associations between RMET performance, social functioning, and cognitive status were analysed using generalised linear models, adjusting for demographic variables. RESULTS: Participants with MCI (b=-.52, 95% CI [-.70, -.33]) and dementia (b=-.78, 95% CI [-1.22, -.34]) showed poorer RMET performance than cognitively normal participants. Participants with MCI and dementia reported reduced social network size (b=-.21, 95% CI [-.40, -.02] and b=-.90, 95% CI [-1.38, -.42], respectively) and participants with dementia reported increased loneliness (b = .36, 95% CI [.06, .67]). In dementia, poorer RMET performance was associated with increased loneliness (b=-.07, 95% CI [-.14, -.00]) and a trend for negative interactions with partners (b=-.37, 95% CI [-.74, .00]), but no significant associations were found in MCI. CONCLUSIONS: MCI and dementia were associated with poor self-reported social function. ToM deficits were related to poor social function in dementia but not MCI. Findings highlight the importance of interventions to address social cognitive deficits in persons with dementia and education of support networks to facilitate positive interactions and social well-being.

Clinical and Biological Correlates of White Matter Hyperintensities in Patients With Behavioral-Variant Frontotemporal Dementia and Alzheimer Disease.

OBJECTIVE: To test the hypothesis that white matter hyperintensities (WMH) in behavioral-variant frontotemporal dementia (bvFTD) and Alzheimer disease (AD) are associated with disease variables such as disease severity, cortical atrophy, and cognition, we conducted a cross-sectional brain MRI study with volumetric and voxel-wise analyses. METHODS: A total of 129 patients (64 bvFTD, 65 AD) and 66 controls underwent high-resolution brain MRI and clinical and neuropsychological examination. Genetic screening was conducted in 124 cases (54 bvFTD, 44 AD, 26 controls) and postmortem pathology was available in 18 cases (13 bvFTD, 5 AD). WMH were extracted using an automated segmentation algorithm and analyses of total volumes and spatial distribution were conducted. Group differences in total WMH volume and associations with vascular risk and disease severity were examined. Syndrome-specific voxel-wise associations between WMH, cortical atrophy, and performance across different cognitive domains were assessed. RESULTS: Total WMH volumes were larger in patients with bvFTD than patients with AD and controls. In bvFTD, WMH volumes were associated with disease severity but not vascular risk. Patients with bvFTD and patients with AD showed distinct spatial patterns of WMH that mirrored characteristic patterns of cortical atrophy. Regional WMH load correlated with worse cognitive performance in discrete cognitive domains. WMH-related cognitive impairments were shared between syndromes, with additional associations found in bvFTD. CONCLUSION: Increased WMH are common in patients with bvFTD and patients with AD. Our findings suggest that WMH are partly independent of vascular pathology and associated with the neurodegenerative process. WMH occur in processes independent of and related to cortical atrophy. Furthermore, increased WMH in different regions contributes to cognitive deficits.