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Background/objectives: To examine the association between white matter hyperintensities (WMH) and cognitive domains such as memory and executive function (EF) across different clinical and biomarker categories of Alzheimer's disease (AD)., Design: Cross-sectional study., Setting: Alzheimer's Disease Neuroimaging Initiative., Participants: A total of 216 cognitively normal (CN) participants and 407 participants with mild cognitive impairment (MCI) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) at baseline., Measurements: Based on the 2018 research framework, participants were classified using AT(N) (amyloid-β deposition [A], pathologic tau [T], and neurodegeneration [(N)]) biomarkers into one of three categories: biomarker negative [A - T- (N)-], amyloid negative but other biomarker positive [A - T ± (N)+ or A - T + (N)±] or amyloid positive [A + T ± (N)±]. Linear regression models were then used to examine the association between WMH and memory composite scores and EF composite scores., Results: Higher WMH burden was associated with worse EF in both CN and MCI subgroups while a significant association between WMH and memory was only found in the MCI subgroup. Furthermore, WMH was associated with EF in the group with A - T ± (N)+ or A - T + (N)± biomarker category, but not for A - T - (N)- (normal biomarker) and A + T ± (N) ± (AD pathology). The association between higher WMH and worse memory was independent of amyloid levels in individuals with MCI with evidence of AD pathology., Conclusion: Vascular disease, as indexed by WMH, independent of AD pathology affects cognitive function in both CN and MCI subgroups. Future studies using the AT(N) research framework should consider white matter lesions as a key biomarker contributing to the clinical presentation of AD., (© 2021 The American Geriatrics Society.)

Leukoaraiosis is one of the main contributors to mild cognitive impairment due to vascular damage (vascular MCI, VMCI), whose pathophysiology has not been fully elucidated yet. We aimed to shed light on such issue using functional MRI (fMRI). Sixteen patients with VMCI were enrolled and compared with twenty-five patients with MCI but without significant vascular damage (non-vascular MCI, NVMCI) and with fifteen healthy controls (HC). They all underwent fMRI with incidental verbal learning paradigm, using a 3T scanner. Differently from cases with NVMCI (versus HC), VMCI patients presented a higher BOLD activation in the right parieto-occipital cortex and a lower activation in the left superior and middle frontal gyri, anterior cingulum and in left fronto-opercular area when compared to HC. Cortical activation evaluated by fMRI may reflect specific patterns of damage and attempt of compensation in patients with MCI and different severity of leukoaraiosis., (Copyright © 2018. Published by Elsevier B.V.)

Leukoaraiosis, also referred to as white-matter hyperintensities (WMHs) or age-related white matter changes, is the most frequently seen lesion on brain magnetic resonance images (MRI) in the elderly. LA is a subject of intense research interest, and is correlated with stroke, cognitive impairment or dementia, disturbances, affective disorders, and poor prognoses. Rapid advances in neuroimaging have enabled greater understanding of LA associated with aging-related cognitive decline or dementia. Recently, the techniques of multimodal MRI, such as structural MRI (sMRI), resting-state functional MRI (rs-MRI), cerebrovascular reactivity (CVR), diffusion tensor imaging (DTI), magnetic resonance spectroscopy (MRS), and dynamic contrast-enhanced MRI (DCE-MRI), have been used to explore the underlying mechanism of cognitive impairment in patients with LA. These multimodal MRI techniques may provide further insights into the structural and functional changes of LA with cognitive dysfunction.

Our study aimed to investigate the changes of white matter microstructure of cortico-subcortical pathways using diffusion tensor imaging (DTI), and to explore the relationship between abnormal parameters of DTI and cognitive function underlying in patients with leukoaraiosis (LA).A total of 42 patients with LA and 42 age- and sex-matched healthy controls were recruited from Beijing Chaoyang Hospital, Capital Medical University between January 2012 and December 2012. All the subjects underwent scans of conventional magnetic resonance imaging and DTI, and a comprehensive neuropsychological battery was utilized. The regions of interest (ROIs) were located at the white matter of centrum semiovale, anterior and posterior periventricular white matter, basal ganglia, corpus callosum. The averaged values of mean diffusivity (MD) and fractional anisotropy (FA) were quantified both within white matter lesions (WMLs) and normal appearing white matter (NAWM). A linear regression analysis was performed to assess the association between diffusion parameters and decline in cognitive domains.Patients with LA were associated with comprehensive cognitive function deficits. We found that significantly decreased FA and increased MD in WMLs at the 5 ROIs than that of NAWM and controls (P < .05). The values of FA in NAWM were significantly lower and MD in NAWM were significantly higher at centrum semiovale and posterior periventricular white matter than that of controls (P < .05). The values of FA in WMLs at anterior periventricular white matter were positively related to the performances of cognition in patients with LA (P < .05). The values of FA in NAWM located at anterior periventricular white matter were positively related to the score of Digit-symbol test (r = 0.446, P = .002). The values of FA in NAWM located at anterior periventricular white matter correlated inversely with the Z scores of executive function (r = -0.418, P = .03).In our study, patients with LA exhibited significant cognitive impairment especially in the domains of executive function. The technique of DTI revealed that the reduced FA and increased MD at the corresponding regions of cortico-subcortical pathways in patients with LA. DTI may be of great help for an early pathology of white matter microstructure underlying in patients with LA.

Aims: To describe the contribution of white matter lesions to the long-term neuropsychological profiles of different groups of clinical diagnoses, and to identify neuropsychological predictors of cognitive impairment in a 10-year follow-up., Methods: The Lisbon subcohort of the Leukoaraiosis and Disability (LADIS) study was re-evaluated performing a clinical, functional and cognitive evaluation [including Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale - Cognition (ADAS-Cog) and ADAS-Cog with the extension for vascular impairment (VADAS-Cog), the 9-word version of the California Verbal Learning Test (CVLT-9), the Trail-Making test and the Stroop test] as well as an MRI scan. Using clinical diagnostic criteria, participants were identified as having no cognitive impairment (NI), cognitive impairment but no dementia (CIND) or dementia (DEM), and the effect of time on clinical diagnosis and neuropsychological profiles was analyzed., Results: From the initial group of 66 participants, 37 out of 41 survivors (90%) were re-evaluated (mean age 81.40 years, 57% women). Fifteen patients (41%) had DEM, 12 (32%) CIND and 10 (27%) NI. Over time, the three groups presented distinct profiles in the MMSE [F2, 62 = 15.85, p = 0.000], ADAS [F2, 62 = 15.85, p = 0.000] and VADAS [F2, 48 = 5.87, p = 0.008]. Logistic regression analysis identified higher scores on MMSE (β = 1.14, p = 0.03, OR = 3.13, 95% CI 1.09-8.97) as predictors of NI after 10 years of follow-up., Conclusion: Higher scores on baseline MMSE were the only neuropsychological predictors of NI after 10 years., (© 2016 S. Karger AG, Basel.)

As the ageing population continues to increase, the prevalence of age-related cognitive impairment has been on the rise. Mild cognitive impairment (MCI) is now widely recognised as the early stage of dementia. Mild cognitive impairment is closely associated with cerebral white matter lesions (WMLs), specifically in the case of leukoaraiosis (LA). A previous diffusion tensor imaging (DTI) has demonstrated that white matter changes might damage cognitive function in LA patients, and the cognitive function might decrease with the deterioration of LA. Through consulting and analysing documents, we found that both of them share similarities in risk factors, pathogenesis, pathological changes, and imaging manifestations. The main characteristics of LA patients with MCI (LACI) are the early and apparent manifestations of delayed memory, attention, impaired executive function, and close association with dementia. This analysis of LACI may contribute to an early diagnosis of LACI and provide possible treatment for LACI.