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The COVID-19 pandemic has caused tremendous suffering for patients with dementia and their caregivers. We conducted a survey to study the impact of the pandemic on patients with mild frontotemporal dementia (FTD). Our preliminary findings demonstrate that patients with FTD have significant worsening in behavior and social cognition, as well as suffer greater negative consequences from disruption to health-care services compared to patients with AD. The reduced ability to cope with sudden changes to social environments places patients with FTD at increased vulnerability to COVID-19 infection as well as to poorer clinical and social outcomes. Caregivers of FTD patients also demonstrate high burden during crisis situations. A proportion of patients with FTD benefitted from use of web-based interactive platforms. In this article, we outline the priority areas for research as well as a roadmap for future collaborative research to ensure greatest benefit for patients with FTD and their caregivers.

ObjectiveTo identify the pathophysiologic mechanisms and clinical significance of anosognosia for cognitive decline in mild cognitive impairment.MethodsWe stratified 468 patients with amnestic mild cognitive impairment into intact and impaired awareness groups, determined by the discrepancy between the patient and the informant score on the Everyday Cognition questionnaire. Voxel-based linear regression models evaluated the associations between self-awareness status and baseline β-amyloid load, measured by [18F]florbetapir, and the relationships between awareness status and regional brain glucose metabolism measured by [18F]fluorodeoxyglucose at baseline and at 24-month follow-up. Multivariate logistic regression tested the association of awareness status with conversion from amnestic mild cognitive impairment to dementia.ResultsWe found that participants with impaired awareness had lower [18F]fluorodeoxyglucose uptake and increased [18F]florbetapir uptake in the posterior cingulate cortex at baseline. In addition, impaired awareness in mild cognitive impairment predicted [18F]fluorodeoxyglucose hypometabolism in the posterior cingulate cortex, left basal forebrain, bilateral medial temporal lobes, and right lateral temporal lobe over 24 months. Furthermore, participants with impaired awareness had a nearly 3-fold increase in likelihood of conversion to dementia within a 2-year time frame.ConclusionsOur results suggest that anosognosia is linked to Alzheimer disease pathophysiology in vulnerable structures, and predicts subsequent hypometabolism in the default mode network, accompanied by an increased risk of progression to dementia. This highlights the importance of assessing awareness of cognitive decline in the clinical evaluation and management of individuals with amnestic mild cognitive impairment.

ObjectiveTo identify regional brain metabolic dysfunctions associated with neuropsychiatric symptoms (NPS) in preclinical Alzheimer disease (AD).MethodsWe stratified 115 cognitively normal individuals into preclinical AD (both amyloid and tau pathologies present), asymptomatic at risk for AD (either amyloid or tau pathology present), or healthy controls (no amyloid or tau pathology present) using [18F]florbetapir PET and CSF phosphorylated tau biomarkers. Regression and voxel-based regression models evaluated the relationships between baseline NPS measured by the Neuropsychiatric Inventory (NPI) and baseline and 2-year change in metabolism measured by [18F]fluorodeoxyglucose (FDG) PET.ResultsIndividuals with preclinical AD with higher NPI scores had higher [18F]FDG uptake in the posterior cingulate cortex (PCC), ventromedial prefrontal cortex, and right anterior insula at baseline. High NPI scores predicted subsequent hypometabolism in the PCC over 2 years only in individuals with preclinical AD. Sleep/nighttime behavior disorders and irritability and lability were the components of the NPI that drove this metabolic dysfunction.ConclusionsThe magnitude of NPS in preclinical cases, driven by sleep behavior and irritability domains, is linked to transitory metabolic dysfunctions within limbic networks vulnerable to the AD process and predicts subsequent PCC hypometabolism. These findings support an emerging conceptual framework in which NPS constitute an early clinical manifestation of AD pathophysiology.

Background: Post Stroke Cognitive Impairment (PSCI) is seen in 40‐60% of patients with ischemic strokes. Response of patients with PSCI to structured cognitive rehabilitation is not clearly understood. We evaluated baseline variables that predict response to an eight‐week non‐pharmacological intervention among patients with mild strokes and compared the responses to non‐pharmacological intervention among acute stroke patients with and without chronic cerebrovascular disease (CVD). Method: 139 ischemic stroke survivors were recruited from a tertiary hospital in Singapore. All patients underwent an eight‐week structured group cognitive rehabilitation programme (Figure 1). Baseline, immediate post‐intervention (Immediate‐PI) and 6‐month post intervention (6‐month‐PI) global cognitive and quality of life (QOL) outcomes were assessed by Montreal Cognitive Assessment (MoCA) and Dementia‐Quality of Life (DemQOL). Regression analyses evaluated the influence of cognitive rehabilitation on outcomes. Result: The mean age of subjects were 63.6 (±9.66) with 64.4% males. Baseline MoCA and DemQOL scores were 23.30 (±3.05) and 79.16 (±14.80). At Immediate‐PI, patients with more past strokes (p = 0.033) and severe white matter hyperintensities (WMH) (p = 0.048), benefited less on global cognitive outcome (Table 1). Male patients (p = 0.074) and patients with more severe WMH (p = 0.048) benefited less on QOL outcome (Table 2). At 6‐month‐PI, patients with microhemorrhages in the deep region (p = 0.002) were less likely to sustain cognitive improvement. With every past stroke experienced, patients were less likely to experience an improvement in MoCA score Immediate‐PI (OR = 2.17, 95% CI: 0.980‐4.813, p = 0.056). with severe WMH were less likely to experience an improvement in MoCA scores Immediate‐PI compared to baseline (OR = 2.13, 95% CI: 1.04‐4.38, p = 0.039). Finally, patients with microhemorrhages in the deep region were less likely to retain the improvements in MoCA at 6‐month‐PI (OR = 19.93, 95% CI: 1.04‐384, p = 0.047) Conclusion: Pre‐stroke CVD were associated with worse cognitive and QoL outcomes post cognitive rehabilitation. Understanding factors that result in poor response to rehabilitation will allow clinicians to better select stroke survivors for cognitive rehabilitation. Future research could build on these findings and allocate more resources to these at‐risk groups for post‐stroke care, therefore reducing the global burden of stroke and ensuring a better QOL for stroke survivors. [ABSTRACT FROM AUTHOR]

Background: White matter hyperintensities, a neuroimaging marker of small-vessel cerebrovascular disease and apolipoprotein ε4 (APOE4) allele, are important dementia risk factors. However, APOE4 as a key effect modifier in the relationship between white matter hyperintensities and grey matter volume needs further exploration. Methods: One hundred ninety-two early-stage dementia (including mild cognitive impairment and mild dementia) and 259 cognitively unimpaired participants from a neurocognitive research cohort with neuroimaging data, APOE genotyping, and neuropsychological assessments were studied. We investigated independent and interactive effects of white matter hyperintensities and APOE4 on whole-brain voxel-wise grey matter volume using voxel-based morphometry (uncorrected p < 0.001; minimum cluster size = 100 voxels). We further assessed interactive effects between APOE4 and white matter hyperintensities on global cognition, memory, and executive function in early-stage dementia and cognitively unimpaired participants. Results: Independent of APOE4 status, higher white matter hyperintensity load was associated with greater grey matter atrophy across frontal, parietal, temporal, and occipital lobes in cognitively unimpaired and early-stage dementia subjects. However, interaction analyses and independent sample analyses revealed that APOE4 non-carriers demonstrated greater white matter hyperintensity-associated grey matter atrophy compared to APOE4 carriers in both cognitively unimpaired and early-stage dementia groups. Additional confirmatory analyses among APOE4 non-carriers demonstrated that white matter hyperintensities resulted in widespread grey matter loss. Analyses of cognitive function demonstrated that higher white matter hyperintensity load was associated with worse global (Mini-Mental State Examination, Montreal Cognitive Assessment) and executive function (Color Trails 2) in APOE4 non-carriers compared to APOE4 carriers in early-stage dementia but not cognitively unimpaired participants. Conclusions: The association between white matter hyperintensities and grey matter loss is more pronounced in APOE4 non-carriers than APOE4 carriers in the cognitively unimpaired and early-stage dementia stages. Furthermore, white matter hyperintensity presence results in poorer executive function in APOE4 non-carriers compared to APOE4 carriers. This finding may have significant impact on the design of clinical trials with disease modifying therapies. [ABSTRACT FROM AUTHOR]