bioRxiv Science⌕ Search

Biology subjects

Khondoker, M.

Publications and source records attributed to Khondoker, M..

2 recordsLinked to original sources

Impact of cardiometabolic factors and blood beta-amyloid on the volume of white matter hyperintensities in dementia-free subjects with cognitive complaints

IntroductionWhite matter hyperintensities (WMH) in Alzheimers disease (AD) have traditionally been associated with cerebrovascular diseases. Amyloid {beta} (A{beta}) deposition reportedly contributes to WMHs; however, this relationship remains unclear in dementia-free subjects with cognitive complaints (CC). Here, we explored the relationship between WMHs and cardiometabolic and A{beta} blood biomarkers in a community-based cohort of Latin American CC participants. MethodsWe recruited 112 individuals with CC (69 - 92 YO, 90 females) with available plasma A{beta} biomarkers and cardiometabolic markers (systolic - diastolic blood pressure and glycaemia). WMHs were quantified using a lesion segmentation tool based on SPM12 and segmented using the John Hopkins University (JHU) Atlas and ALVIN segmentation for periventricular and subcortical white matter. Linear multiple regression models were fitted to assess total WMH lesions and the segmented tract, using demographics, cardiometabolic, and A{beta} blood biomarker measures as independent variables. ResultsAfter multiple comparison corrections, diastolic blood pressure was associated with WMHs, specifically in the right anterior thalamic radiation, left cingulum, minor forceps, and subcortical ALVIN segmentation. Glycaemia was associated with WMH volume in forceps major, forceps minor, and right fronto-occipital fasciculi. Conversely, A{beta} blood biomarkers and systolic blood pressure showed no association with WMH overall or in specific tracts. ConclusionOur findings suggest that, in dementia-free CC individuals, WMH volume was more related to cardiometabolic factors, whereas A{beta} blood biomarkers might be of less relevance. Dementia prevention strategies in individuals might be a useful focus for managing high peripheral vessel resistance and endothelial damage due to hypertension and hyperglycaemia.

neuroscience↗

Impact of Sex and APOE Status on Spatial Navigation in Pre-symptomatic Alzheimer’s disease

INTRODUCTIONSpatial navigation is emerging as a critical factor in identifying pre-symptomatic Alzheimer pathophysiology, with the impact of sex and APOE status on spatial navigation yet to be established.\n\nMETHODSWe estimate the effects of sex on navigation performance in 27,308 individuals (50-70 years [benchmark population]) by employing a novel game-based approach to cognitive assessment using Sea Hero Quest. The effects of APOE genotype and sex on game performance was further examined in a smaller lab-based cohort (n = 44).\n\nRESULTSBenchmark data showed an effect of sex on wayfinding distance, duration and path integration. Importantly in the lab cohort, performance on allocentric wayfinding levels was reduced in{varepsilon} 4 carriers compared to{varepsilon} 3 carriers, and effect of sex became negligible when APOE status was controlled for. To demonstrate the robustness of this effect and to ensure the quality of data obtained through unmonitored at-home use of the Sea Hero Quest game, post-hoc analysis was carried out to compare performance by the benchmark population to the monitored lab-cohort.\n\nDISCUSSIONAPOE {varepsilon}4 midlife carriers exhibit changes in navigation pattern before any symptom onset. This supports the move towards spatial navigation as an early cognitive marker and demonstrates for the first time how the utility of large-scale digital cognitive assessment may hold future promise for the early detection of Alzheimers disease. Finally, benchmark findings suggest that gender differences may need to be considered when determining the classification criteria for spatial navigational deficits in midlife adults.

neuroscience↗