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Dopamine (DA) signaling is critical for optimal cognitive aging, especially in prefrontal-parietal and fronto-striatal networks. Single nucleotide polymorphisms associated with dopamine regulation, COMT Val158Met and DRD2 C957T , stand to exert influence on executive function performance via neural properties. The current study investigated whether longitudinal thinning of mesocortical regions is related to COMT and DRD2 genetic predisposition and associated with decline in executive function over four-years. N =235 healthy adults aged 20–94 years were recruited, with n =124 returning 4-years later. Latent mixed effects modeling revealed dopamine-related thinning in several frontal, parietal, and cingulate regions as well as decline in verbal fluency category switching across 4-years. Mesocortical thinning was also related to switching performance. Greater cortical thinning interacted with DA-genotype risk for lower DA-availability to predict poorer switching performance in parietal and posterior cingulate cortex. These findings lend support to the notion that early-life factors, such as genetic influence on neurotransmitter function, play a role in cognitive and brain aging and their linked association. • Dopamine signaling decreases significantly with aging and predicts poorer cognition. • Genetic polymorphisms regulating dopamine availability predict cognitive performance. • Greater cortical thinning seen in genotypes at risk for lower synaptic availability. • Dopamine-related thinning was associated with poorer executive function performance. • Genetic predisposition to lower dopamine availability impacts neurocognitive aging. [ABSTRACT FROM AUTHOR]

White matter hyperintensities (WMH) are associated with cortical thinning. Although they are primarily detected in older participants, these lesions can appear in younger and midlife individuals. Here, we tested whether WMH are associated with cortical thinning in relatively younger (26–50 years) and relatively older (58–84) participants who were free of dementia, and how these associations are moderated by WMH localization. WMH were automatically quantified and categorized according to the localization of three classes of white matter tracts: association, commissural and projection fibers. Mediation analyses were used to infer whether differences in cortical thickness between younger and older participants were explained by WMH. Our results revealed that total WMH explained between 20.6 % and 65.5 % of the effect of age on cortical thickness in AD-signature regions including the lateral temporal lobes and supramarginal gyrus, among others. This mediation was slightly stronger for projection WMH, although it was still significant for association and commissural WMH. These results suggest that there is an interplay between vascular and AD causes of cognitive impairment that starts at younger ages. • White matter hyperintensities (WMH) are apparent in middle-age. • WMH correlate with cortical thickness, especially in younger adults. • WMH explain up to 65.6 % of age-related cortical thickness differences. • The effect of WMH on atrophy starts during the mid-life. [ABSTRACT FROM AUTHOR]

Alterations in grey matter (GM) and white matter (WM) are associated with memory impairment across the neurocognitive aging spectrum and theorised to spread throughout brain networks. Functional and structural connectivity (FC,SC) may explain widespread atrophy. We tested the effect of SC and FC to the hippocampus on cortical thickness (CT) of connected areas. In 419 (223 F) participants (age mean =73 ± 8) from the Alzheimer's Disease Neuroimaging Initiative, cortical regions associated with memory (Rey Auditory Verbal Learning Test) were identified using Lasso regression. Two structural equation models (SEM), for SC and resting-state FC, were fitted including CT areas, and SC and FC to the left and right hippocampus (LHIP,RHIP). LHIP (β =-0.150, p =<.001) and RHIP (β =-0.139, p =<.001) SC predicted left temporopolar/rhinal CT; RHIP SC predicted right temporopolar/rhinal CT (β =-0.191, p =<.001). LHIP SC predicted right fusiform/parahippocampal (β =-0.104, p =.011) and intraparietal sulcus/superior parietal CT (β =0.101, p =.028). Increased RHIP FC predicted higher left inferior parietal CT (β =0.132, p =.042) while increased LHIP FC predicted lower right fusiform/parahippocampal CT (β =-0.97; p =.023). The hippocampi may be epicentres for cortical thinning through disrupted connectivity. • Connectivity to the hippocampi is associated with grey matter alterations. • Both structural and functional connectivity can predict grey matter thickness. • The study supports the idea that the hippocampi are an epicentre for atrophy. [ABSTRACT FROM AUTHOR]

• Elderly chimpanzees show regional cortical thinning compared to younger individuals. • Elderly chimpanzees show greater rightward asymmetries compared to younger apes. • Age-related differences in cognition were associated with loss in cortical thickness. Humans and chimpanzees are genetically similar and share a number of life history, behavioral, cognitive and neuroanatomical similarities. Notwithstanding, our understanding of age-related changes in cognitive and motor functions in chimpanzees remains largely unstudied despite recent evident demonstrating that chimpanzees exhibit many of the same neuropathological features of Alzheimer's disease observed in human postmortem brains. Here, we examined age-related differences in cognition and cortical thickness measured from magnetic resonance images in a sample of 215 chimpanzees ranging in age between 9 and 54 years. We found that chimpanzees showed global and region-specific thinning of cortex with increasing age. Further, within the elderly cohort, chimpanzees that performed better than average had thicker cortex in frontal, temporal and parietal regions compared to chimpanzees that performed worse than average. Independent of age, we also found sex differences in cortical thickness in 4 brain regions. Males had higher adjusted cortical thickness scores for the caudal anterior cingulate, rostral anterior cingulate, and medial orbital frontal while females had higher values for the inferior parietal cortex. We found no evidence that increasing age nor sex was associated with asymmetries in cortical thickness. Moreover, age-related differences in cognitive function were only weakly associated with asymmetries in cortical thickness. In summary, as has been reported in humans and other primates, elderly chimpanzees show thinner cortex and variation in cortical thickness is associated with general cognitive functions. [ABSTRACT FROM AUTHOR]

• In CN, WMH associates with frontotemporal cortical thickness independent of regional Aβ. • In MCI, WMH associates with temporal and cingulate thickness independent of regional Aβ. • In MCI, temporal Aβ associates with temporal cortical thickness independent of WMH. • No interactions of WMH with regional Aβ on regional cortical thickness were found. • WMH, composite regional Aβ and cortical thickness independently predicted progression to dementia. White matter hyperintensities (WMH) and β-amyloid (Aβ) accumulation have both been linked to neurodegeneration in Alzheimer's disease (AD). However, the independent effects of global WMH and regional Aβ on the corresponding regional cortical thickness have not been investigated. Here, we evaluated 280 cognitively normal (CN), 450 mild cognitive impairment (MCI), and 63 individuals with AD dementia separately. In CN individuals, only WMH was associated with lower cortical thickness in fronto-temporal regions, independent of regional Aβ deposition in the corresponding cortical regions. In MCI individuals, the spatial pattern of independent WMH associations was predominantly in temporal and cingulate regions, while independent regional Aβ associations were now evident in temporal regions. No regional interactions were found. In non-demented individuals and MCI individuals alone, we found that global WMH, composite regional Aβ burden and cortical thickness in AD-associated regions all independently predicted progression to AD dementia. Our findings suggest that the independent effects of global WMH and regional Aβ on regional cortical thickness are spatially different, converging in temporal regions in MCI individuals. [ABSTRACT FROM AUTHOR]

• Vascular disease is strongly linked to the canonical pattern AD of atrophy. • WMH is correlated with lower cortical thickness in normal controls, less in AD. • Cortical loss in CN is co-localized with the canonical pattern of AD atrophy. White matter signal abnormalities (WMSA), either hypo- or hyperintensities in MRI imaging, are considered a proxy of cerebrovascular pathology and contribute to, and modulate, the clinical presentation of Alzheimer's disease (AD), with cognitive dysfunction being apparent at lower levels of amyloid and/or tau pathology when lesions are present. To what extent the topography of cortical thinning associated with AD may be explained by WMSA remains unclear. Cortical thickness group difference maps and subgroup analyses show that the effect of WMSA on cortical thickness in cognitively normal participants has a higher overlap with the canonical pattern of AD, compared to AD participants. (Age and sex-matched group of 119 NC (AV45 PET negative, CDR = 0) versus 119 participants with AD (AV45 PET-positive, CDR > 0.5). The canonical patterns of cortical atrophy thought to be specific to Alzheimer's disease are strongly linked to cerebrovascular pathology supporting a reinterpretation of the classical models of AD suggesting that a part of the typical AD pattern is due to co-localized cortical loss before the onset of AD. [ABSTRACT FROM AUTHOR]

Motor neuron diseases encompass a divergent group of conditions with considerable differences in clinical manifestations, survival, and genetic vulnerability. One of the key aspects of clinical heterogeneity is the preferential involvement of upper (UMN) and lower motor neurons (LMN). While longitudinal imaging patters are relatively well characterized in ALS, progressive cortical changes in UMN,- and LMN-predominant conditions are seldom evaluated. Accordingly, the objective of this study is the juxtaposition of longitudinal trajectories in 3 motor neuron phenotypes; a UMN-predominant syndrome (PLS), a mixed UMN-LMN condition (ALS), and a lower motor neuron condition (poliomyelitis survivors). A standardized imaging protocol was implemented in a prospective, multi-timepoint longitudinal study with a uniform follow-up interval of 4 months. Forty-five poliomyelitis survivors, 61 patients with amyotrophic lateral sclerosis (ALS), and 23 patients with primary lateral sclerosis (PLS) were included. Cortical thickness alterations were evaluated in a dual analysis pipeline, using standard cortical thickness analyses, and a z-score-based individualized approach. Our results indicate that PLS patients exhibit rapidly progressive cortical thinning primarily in motor regions; ALS patients show cortical atrophy in both motor and extra-motor regions, while poliomyelitis survivors exhibit cortical thickness gains in a number of cerebral regions. Our findings suggest that dynamic cortical changes in motor neuron diseases may depend on relative UMN and/or LMN involvement, and increased cortical thickness in LMN-predominant conditions may represent compensatory, adaptive processes. [ABSTRACT FROM AUTHOR]

• Shorter cerebral systolic peak timing is associated with cortical thinning in older adults. • Cerebral systolic peak timing could not be predicted from its peripheral indices such as pulse plethysmography systolic peak timing. • Higher latency between systolic peak timing of total arterial blood flow and cerebrospinal fluid is correlated with cortical thinning in older adults. Aging is accompanied by global brain atrophy occurring unequally across the brain. Cortical thinning is seen with aging with a larger loss in the frontal and temporal subregions. We explored the link between regional cortical thickness and regional cerebral pulsatility. Sixty healthy individuals were divided into two age groups, young (aged 19–31) and older (aged 65–75) adults. Each participant underwent a near-infrared spectroscopy (NIRS) scan to index regional brain pulsatility from cerebral pulse-transit-time-to-the peak-of-the-pulse (PTTp), an anatomical magnetic resonance imaging (MRI) and a phase-contrast MRI (PC-MRI) scan to measure arterial and cerebrospinal fluid (CSF) pulsatility. In older adults, the greatest association between cerebral pulsatility and cortical thickness was found in superior and middle temporal and superior, middle and inferior frontal areas, which are the regions perfused first by the internal carotid arteries. This association dropped in the postcentral and superior parietal regions. These findings suggest higher brain pulsatility as a potential risk factor contributing to cortical thinning for some brain regions more than others. [ABSTRACT FROM AUTHOR]

Abstract Coexisting Alzheimer's disease (AD) pathology is common in patients with dementia with Lewy bodies (DLB). To evaluate the cortical thinning in patients with DLB considering the effect of amyloid-β (Aβ), we compared the regional cortical thickness between control subjects and patients with DLB with abnormal dopamine transporter imaging. Seventeen (43.6%) of 39 patients with DLB and no control subjects had significant Aβ deposition on 18F-florbetaben positron emission tomography. Compared to control (n = 15), Aβ-negative DLB group (n = 21) had cortical thinning in the bilateral insula, entorhinal, basal frontal, and occipito-parietal cortices. Compared to Aβ-negative DLB, Aβ-positive DLB group (n = 15) had a lower cortical thickness in the AD-prone brain regions in addition to the bilateral occipital, basal frontal, and somatomotor cortices. After controlling for the amount of Aβ deposition, DLB group had cortical thinning in the same regions affected in the Aβ-negative DLB group. In summary, patients with DLB had an Aβ-independent cortical thinning, while Aβ was associated with additional cortical thinning in the AD-prone brain regions and the aggravation of DLB-specific cortical thinning. [ABSTRACT FROM AUTHOR]