Background The medial temporal lobe (MTL) is extensively connected to the rest of the brain through two specific networks: the anterior-temporal (AT) and the posterior-medial (PM) systems. As neurodegeneration is thou...
Background The medial temporal lobe (MTL) is extensively connected to the rest of the brain through two specific networks: the anterior-temporal (AT) and the posterior-medial (PM) systems. As neurodegeneration is thought to occur along specific networks, our aim was to evaluate whether atrophy in perirhinal (PRC) vs parahippocampal cortices (PHC) - two MTL nodes of the AT vs PM systems, respectively - covary over time with distinct brain regions reflecting the AT vs PM networks. Method Longitudinal T1-weighted images (up to 3 scans, span: 1.73±0.49 years) of 117 Ab- Cognitively Normal elderly (CN), 65 Ab+ CN, 148 Ab+ MCI and 19 Ab+ AD individuals from ADNI were included. Annualized atrophy rates of PRC and PHC were estimated with an unbiased deformation-based morphometry method. Whole-brain cortical thickness annualized atrophy rates were estimated using ANTs. Voxel-wise correlations between MTL measures and whole-brain maps were performed to highlight structural covariance patterns [P cluster(corr) <0.05, P voxel(uncorr) <0.01]. Functional connectivity analyses (seed-based) were employed to define the AT and PM networks [P cluster(corr) <0.05, P voxel(uncorr) <0.01] in an independent sample of 68 CN older adults. The overlap between structural covariance patterns and the AT and PM networks was visually inspected. T-maps from the voxel-wise correlations were used to calculate goodness of fit (GOF) indices with the AT and PM networks (GOF=t inside -t outside ). Result Functional connectivity analyses revealed two distinct networks: the AT network encompasses the amygdala and the temporopolar cortex extending posteriorly to inferior and middle temporal gyri while the PM network encompasses the posterior cingulate cortex, the precuneus, the cuneus, the angular and occipital gyri and the right insula (Figure 1-a). PRC structurally covaried with the amygdala and the left temporopolar cortex, overlapping with the AT network (Figure 1-b,c). In contrast, PHC covaried with t
Background This pilot study investigates the psychometric properties of a mobile app-based memory task, the mobile cognitive app performance platform (mCAPP), to detect memory changes associated with preclinical Alzhe...
Background This pilot study investigates the psychometric properties of a mobile app-based memory task, the mobile cognitive app performance platform (mCAPP), to detect memory changes associated with preclinical Alzheimer’s Disease (AD). A mobile, reliable, valid, short, and engaging cognitive assessment is necessary for early detection and tracking change in individuals at risk for AD. Method Participants included 30 older adults (60% female; age=70.9±4.1, years of education=16±2.5; 73% Caucasian) with normal cognition who are enrolled in the penn ADRC cohort. The mCAPP memory task includes learning and then matching hidden card pairs and incorporates increasing memory load, pattern separation features (lure vs. non-lure), and spatial memory (moving target cards). Participants completed the NACC UDS3 neuropsychological battery and additional cognitive measures, within six months of the mCAPP testing and twenty participants completed a high-resolution structural MRI scan. Result Almost all participants found the difficulty level of the mCAPP game to be “just right” (92%), 65% reported they enjoyed the game and 43% reported they would play it for fun. Higher average number of guesses at higher memory load levels was correlated with lower story learning and memory, digit span, trail making test (TMT) B and olfactory performance (p<0.05). Higher average duration of time on the higher memory load levels was correlated with worse performance on digit span, animal naming, TMT A and B, and olfaction (p<0.05). The number of guesses and duration of time on lure vs. non-lure trials was significantly different, with more guesses and more time required for the lure trials (requires pattern separation) at higher memory load levels [Guesses: 8 card, t(29)=5.6,p<0.001; 12 cards, t(29)=4.5,p<0.001; Duration: 8 cards, t(29)=6.9,p<0.001; 12 cards, t(29)=5.9,p<0.001]. At some higher memory load levels, longer duration of time on trials correlated with smaller mean thickness of the par
Background Age effects on the hippocampus are well established, but age-effects on adjacent cortical regions less so. Moreover, aging has often been investigated using cross-sectional designs, seldomly separating agin...
Background Age effects on the hippocampus are well established, but age-effects on adjacent cortical regions less so. Moreover, aging has often been investigated using cross-sectional designs, seldomly separating aging effects from the effects of β-amyloid. We investigate the effect of aging on medial temporal lobe (MTL) subregions cross-sectionally and longitudinally in β-amyloid-negative (A-) cognitively normal (CN) older adults and the role of tau pathology, a potential mediator. Method T1-MRI scans of 191 A- CN adults (71.7±6.0 years, 52.4% male) from ADNI-GO/2 were segmented using a specialized method for MTL morphometry to obtain anterior/posterior hippocampus volumes, entorhinal cortex (ERC), Brodmann areas (BA) 35/36 and parahippocampal cortex thickness. Annualized atrophy rates were estimated with an unbiased deformation-based morphometry method using follow-up MRI scans within 2.1±0.1 years. All MTL subregions were corrected for sex and hippocampal volume also for intracranial volume. Cerebrospinal fluid levels of phosphorylated tau (p-tau) were logtransformed. β-amyloid status (A+/-) was determined using a standard cutoff for amyloid PET. Result Cross-sectionally age was significantly associated with hippocampal volumes and BA35 (Figure 1-2). Longitudinally, MTL subregions showed atrophy rates significantly smaller than 0, and paired t-tests revealed a significantly faster atrophy rate for BA35 than the other cortical regions (Figure 1). Older age was associated with increased atrophy rates in hippocampal volumes, ERC and BA35 (Table 1, Figure 3). A significant association was found for p-tau levels with anterior and posterior hippocampus (trend) and with anterior and posterior hippocampal atrophy rates (Figure 4), which remained similar after a correction for age. Since the association for anterior/posterior hippocampus was similar, we performed a mediation analysis for total hippocampus, showing that aging leads to smaller hippocampal volumes (p<0.05) a
Brain aging is a multifaceted and highly heterogeneous process accompanied by several pathologies. Here, we propose a method for dissecting the heterogeneity of neuropathologic processes occurring with aging using mac...
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ISBN:
(数字)9798350313338
ISBN:
(纸本)9798350313345
Brain aging is a multifaceted and highly heterogeneous process accompanied by several pathologies. Here, we propose a method for dissecting the heterogeneity of neuropathologic processes occurring with aging using machine learning and leveraging information from cross-sectional and longitudinal data. Specifically, we hypothesize that the heterogeneity observed in brain aging can be captured by a set of patterns consistent with longitudinal trajectories of brain change, the latter directly capturing evolving neuropathologic processes on an individual basis. Applying the method to structural magnetic resonance imaging data from the BLSA study, we derived five distinct, reproducible, and clinically informative components of neuroanatomical brain change, highlighting the method’s potential as a tool for precision medicine.
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