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Background: Mild behavioural impairment (MBI) is proposed as a diagnostic construct to identify dementia‐free individuals with sustained neuropsychiatric symptoms as an early manifestation of dementia. Our previous study has demonstrated that MBI predicts faster cognitive decline and progression to dementia. Other studies have shown that MBI was associated with Alzheimer's disease biomarkers for Aβ and tau. However, cerebrovascular disease (CeVD), which is another critical pathology in dementia, has not been investigated in MBI. Here, we sought to test brain free‐water (FW) alterations, a marker for CeVD, in MBI compared with non‐MBI participants and their associations with longitudinal changes in cognition, function, and neuropsychiatric symptoms. Method: Longitudinal global cognitive scores, clinical dementia rating sum‐of‐boxes (CDR‐SoB), neuropsychiatric inventory (NPI) scores, over 5 years were reported in 281 dementia‐free participants (40 MBI and 241 non‐MBI). MBI was diagnosed using established criteria. All participants underwent T1‐weighted structural and diffusion MRI at baseline. FW imaging method was applied to derive individual‐level white matter (WM) and grey matter (GM) FW maps from diffusion MRI. We compared baseline GM‐FW and WM‐FW between non‐MBI and MBI subjects. We then tested the associations of MBI‐related FW increase with baseline and longitudinal changes in global cognition, CDR‐SB, and NPI scores using linear regression models. Result: MBI had greater GM‐FW in executive control (prefrontal), motor sensory (precentral), attention (insula) and memory (left temporal and right cingulate and cuneus) networks and widespread higher WM‐FW compared with non‐MBI (Fig‐1). Both higher GM‐FW and WM‐FW were associated with lower global cognition, higher CDR‐SB, and higher NPI scores across all participants at baseline (Table‐1). There was no interaction effect of MBI status on such association. Moreover, higher baseline GM‐FW and WM‐FW were associated with longitudinal worsening in global cognition, CDR‐SB, and NPI scores (Table‐2). Interestingly, such associations were greater in MBI than in non‐MBI (Fig‐2). Conclusion: This study demonstrated that MBI was associated with increased brain FW, which may have contributed to the relationship between persistent neuropsychiatric disturbances and clinical and cognitive outcomes. Early detection of cerebrovascular‐related FW alteration may allow for timely management of MBI individuals before development of dementia. [ABSTRACT FROM AUTHOR]

Objective: Sleep disturbances were found to be associated with more behavioral and psychological symptoms (BPS) in early patients with Alzheimer's disease (AD). However, data on preclinical stages of dementia are lacking. Hence, the present study sought to investigate the association between sleep disturbances and BPS in dementia-free elderly with varying severity of cognitive impairment in an Asian sample.Methods: Community-living elderly were recruited and administered a comprehensive cognitive battery (vascular dementia battery [VDB]) and the Neuropsychiatric Inventory to assess symptoms of sleep disturbances and BPS. Severity of cognitive impairment was diagnosed and classified as no cognitive impairment (NCI), cognitive impairment-no dementia (CIND) -mild (1-2 impaired domains on the VDB), and CIND-moderate (≥3 impaired domains on the VDB). Analysis of variance was conducted to assess the associations between the presence of sleep disturbances and BPS scores in each diagnostic group. Logistic regression was used to examine whether the coexistence of sleep disturbances and other BPS was associated with CIND-moderate, which is known to carry a higher risk of progression to AD.Results: Among 839 elderly, 79 (9.4%) reported sleep disturbances. Participants with sleep disturbances had higher total BPS burden than those without among CIND participants but not in NCIs. Furthermore, CIND-moderate participants with sleep disturbances had more delusions, hallucinations, anxiety, depression, irritability, aberrant motor behavior, and appetite change ( P < .05). The presence of both sleep disturbances and other BPS was associated with CIND-moderate (odds ratio: 2.5, 95% confidence interval: 1.1-5.5).Conclusions: Sleep disturbances are associated with higher total BPS burden and specific BPS among elderly patients with cognitive impairment, particularly those with CIND moderate, which carries higher risk of developing dementia. [ABSTRACT FROM AUTHOR]

Background: Neurocognitive and neuropsychiatric symptoms are essential clinical manifestations of age-related cognitive impairment, yet their patterns of co-existence remain unclear through the cognitive continuum., Objective: To examine the associations of person-centered cluster-derived patterns, based on a comprehensive collection of domain-specific cognitive and neuropsychiatric assessments, with neuroimaging markers and dementia risk., Methods: 641 participants were included in the analysis from memory clinics in Singapore. Latent class analysis was applied to define clusters of individuals with different clinical patterns. The associations between identified clinical groups with neuroimaging markers of cerebrovascular diseases and neurodegeneration were analyzed using logistic regression models. Cox proportional hazard models were applied for incident dementia., Results: Three latent classes differing in neurocognitive and neuropsychiatric impairment were identified (Class 1 "memory impairment only"; Class 2 "global cognitive impairment"; Class 3 "global cognitive and neuropsychiatric impairment"). Compared with Class 1, Class 2 and 3 were associated with smaller brain volumes, moderate-to-severe cortical atrophy and medial temporal lobe atrophy, and the presence of all cerebrovascular lesions. Moreover, compared with Class 2, Class 3 had smaller brain volumes, moderate-to-severe cortical atrophy and presence of intracranial stenosis. Additionally, compared to Class 1, Class 2 (hazard ratio [HR] = 3.84, 95%CI 2.11-7.00), and Class 3 (HR = 6.92, 95%CI 2.84-16.83) showed an increased risk of incident dementia., Conclusions: Participants characterized by multi-domain cognitive impairment and co-occurrence of cognitive and neuropsychiatric impairment showed the highest risk of incident dementia, which may be attributed to both neurodegenerative and cerebrovascular pathologies., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.