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Background: Cortical atrophy is a key neuroimaging feature of dementia. However, the role of subcortical gray matter reduction in cognitive impairment has not been explored extensively.Objectives: We examined the risk factors of subcortical structures on neuroimaging and their association with cognitive impairment and dementia.Methods: Data from two studies were used: a subsample from the Epidemiology of Dementia in Singapore (EDIS) study of non-demented community-dwelling subjects (n = 550) and a case-control study. Subjects underwent similar neuropsychological tests and brain MRI. Subcortical volumes of accumbens, amygdala, caudate, pallidum, putamen, thalamus, hippocampus, and brainstem were measured. Cognitive impairment no dementia (CIND), dementia and its subtypes, vascular cognitive impairment (VCI), were defined using accepted criteria. Cognitive function was also expressed as both composite and domain-specific Z-scores.Results: In the EDIS study, age, female gender, Malay ethnicity, diabetes, lacunar-infarcts, and white matter lesions were the most important risk factors for subcortical atrophy. Moreover, smaller volumes of accumbens, amygdala, caudate, thalamus, and brainstem were significantly associated with lower cognitive composite Z-scores. With respect to clinical outcomes in the case-control study, structures such as the accumbens, caudate, putamen, and hippocampus were associated with both CIND and dementia. Smaller caudate and pallidum volumes were related to VCI whereas amygdalar atrophy was only associated with non-VCI. Furthermore, subcortical atrophy was related to both VCI and non-VCI.Conclusion: Subcortical gray matter atrophy is not only observed in dementia, but also in the preclinical stages of cognitive impairment. Furthermore, besides VCI, subcortical structures were also related to non-VCI. [ABSTRACT FROM AUTHOR]

Cortical thickness has been suggested to be one of the most important markers of cortical atrophy. In this study, we examined potential risk factors of cortical thickness and its association with cognition in an elderly Asian population from Singapore. This is a cross-sectional study among 572 Chinese and Malay patients from the ongoing Epidemiology of Dementia in Singapore (EDIS) Study, who underwent comprehensive examinations including neuropsychological testing and brain magnetic resonance imaging (MRI). Cortical thickness (in micrometers) was measured using a model-based automated procedure. Cognitive function was expressed as composite and domain-specific Z-scores. Cognitive impairment was categorized into cognitive impairment no dementia (CIND)-mild, CIND-moderate, and dementia in accordance with accepted criteria. Linear regression models were used to examine the association between various risk factors and cortical thickness. With respect to cognition as outcome, both linear (for Z-scores) and logistic (for CIND/dementia) regression models were constructed. Initial adjustments were made for age, sex, and education, and subsequently for other cardiovascular risk factors and MRI markers. Out of 572 included patients, 171 (29.9%) were diagnosed with CIND-mild, 197 (34.4%) with CIND-moderate, and 28 (4.9%) with dementia. Risk factors related to a smaller cortical thickness were increased age, male sex, Malay ethnicity, higher blood glucose, and body mass index levels and presence of lacunar infarcts on MRI. Smaller cortical thickness was associated with CIND moderate/dementia [odds ratio (OR) per standard deviation (SD) decrease: 1.70; 95% confidence interval (CI): 1.19-2.44, P = 0.004] and with composite Z-score reflecting global cognitive functioning [mean difference per SD decrease: -0.094; 95% CI: -0.159; -0.030, P = 0.004]. In particular, smaller cortical thicknesses in the occipital and temporal lobes were related to cognitive impairment. Finally, in terms of specific cognitive domains, the most significant associations were found for executive function, visuoconstruction, and visual memory. Smaller cortical thickness is significantly associated with cognitive impairment, suggesting a contribution of diffuse cortical atrophy beyond the medial temporal lobe to cognitive function. These findings suggest that cortical thinning is a biomarker of neurodegenerative changes in the brain not only in dementia, but also in its preclinical stages.

Cerebral microbleeds (CMBs) are considered to be a novel marker of cerebral small vessel disease. However, the link with cognitive impairment remains unclear. We investigated whether CMBs-independent of other traditional markers of cerebral small vessel disease-are related to cognition. Chinese subjects from the population-based Singapore Chinese Eye Study, who failed an initial cognitive screening and were recruited into the ongoing Epidemiology of Dementia in Singapore Study, underwent neuropsychological testing and 3 T brain magnetic resonance imaging. The presence and number of CMBs were graded using Brain Observer Microbleed Scale on susceptibility-weighted images. Other magnetic resonance imaging lesions that were graded included presence of lacunes, white matter lesion, and total brain volumes. A comprehensive neuropsychological battery was administered and cognitive function was summarized as composite and domain-specific Z-scores. Among 282 subjects, 91 had any CMBs (32.3%), of whom 36 (12.8%) had multiple CMBs. CMBs were-independent of cardiovascular risk factors and other markers of cerebral small vessel disease-significantly associated with poorer cognitive function as reflected by composite Z-score (mean difference per CMB increase: -0.06; 95% confidence interval: -0.11, -0.01] and with domain-specific Z-scores including executive function, attention, and visuoconstruction. Among Chinese subjects CMBs were, independent of other concomitant markers of cerebral small vessel disease, associated with poorer cognitive function.