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Objective: To create a comprehensive map of strategic lesion network localizations for neurological deficits, and identify prognostic neuroimaging biomarkers to facilitate the early detection of patients with a high risk of poor functional outcomes in acute ischemic stroke (AIS). Methods: In a large‐scale multicenter study of 7,807 patients with AIS, we performed voxel‐based lesion‐symptom mapping, functional disconnection mapping (FDC), and structural disconnection mapping (SDC) to identify distinct lesion and network localizations for National Institutes of Health Stroke Scale (NIHSS) score. Impact scores were calculated based on the odds ratios or t‐values of voxels from voxel‐based lesion‐symptom mapping, FDC, and SDC results. Ordinal regression models were used to investigate the predictive value of the impact scores on functional outcome (defined as the modified Rankin score at 3 months). Results: We constructed lesion, FDC, and SDC maps for each item of the NIHSS score, which provided insights into the neuroanatomical substrate and network localization of neurological function deficits after AIS. The lesion impact score of limb ataxia, the SDC impact score of limb deficit, and FDC impact score of sensation and dysarthria were significantly associated with modified Rankin Scale at 3 months. Adding the SDC impact score, FDC impact score, and lesion impact score to the NIHSS total score improved the performance in predicting functional outcomes, as compared with using the NIHSS score alone. Interpretation: We constructed comprehensive maps of strategic lesion network localizations for neurological deficits that were predictive of functional outcomes in AIS. These results may provide specifically localized targets for future neuromodulation therapies. ANN NEUROL 2023;94:572–584 [ABSTRACT FROM AUTHOR]

The A/T/N research framework has been proposed for the diagnosis and prognosis of Alzheimer's disease (AD). However, the spatial distribution of ATN biomarkers and their relationship with cognitive impairment and neuropsychiatric symptoms (NPS) need further clarification in patients with AD. We scanned 83 AD patients and 38 cognitively normal controls who independently completed the mini‐mental state examination and Neuropsychiatric Inventory scales. Tau, Aβ, and hypometabolism spatial patterns were characterized using Statistical Parametric Mapping together with [18F]flortaucipir, [18F]florbetapir, and [18F]FDG positron emission tomography. Piecewise linear regression, two‐sample t‐tests, and support vector machine algorithms were used to explore the relationship between tau, Aβ, and hypometabolism and cognition, NPS, and AD diagnosis. The results showed that regions with tau deposition are region‐specific and mainly occurred in inferior temporal lobes in AD, which extensively overlaps with the hypometabolic regions. While the deposition regions of Aβ were unique and the regions affected by hypometabolism were widely distributed. Unlike Aβ, tau and hypometabolism build up monotonically with increasing cognitive impairment in the late stages of AD. In addition, NPS in AD were associated with tau deposition closely, followed by hypometabolism, but not with Aβ. Finally, hypometabolism and tau had higher accuracy in differentiating the AD patients from controls (accuracy = 0.88, accuracy = 0.85) than Aβ (accuracy = 0.81), and the combined three were the highest (accuracy = 0.95). These findings suggest tau pathology is superior over Aβ and glucose metabolism to identify cognitive impairment and NPS. Its results support tau accumulation can be used as a biomarker of clinical impairment in AD. [ABSTRACT FROM AUTHOR]

Background and purpose: The anterior and posterior hippocampal networks represent verbal and spatial memory, respectively, and may play different roles in the pathological mechanism of amnestic mild cognitive impairment (aMCI) and non‐amnestic MCI (naMCI), which has not been explored. Methods: A total of 990 older adults with 791 normal controls (NCs) (65 ± 6 years, 502 women), 140 aMCI (66 ± 7 years, 84 women) and 59 naMCI (66 ± 7 years, 38 women) were included. A multivariate method, partial least squares, was used to assess the structural covariance networks of the anterior hippocampus (aHC) and posterior hippocampus (pHC), and their relationships with verbal memory and spatial memory in the three groups. Results: Three aHC and pHC structural covariance network patterns emerged: (1) the age pattern; (2) the specific aMCI pattern; and (3) the spatial memory pattern. Furthermore, aMCI patients had more extensive and severe damage in the three patterns, and correlated with greater decline in verbal memory, which was mainly characterized by the aHC network. Conclusions: The aMCI and naMCI showed different patterns and damage in the structural covariance networks, and functional segregation of the aHC and pHC networks still exists in the process of pathological aging. A potential neural explanation is provided for the conversion of aMCI and naMCI into different types of dementia in the future. [ABSTRACT FROM AUTHOR]

Background: Weight loss in late life is associated with a higher risk of dementia and higher mortality. However, the temporal and etiological associations between weight loss and mild cognitive impairment (MCI) remain unclear. Method: We examined 709 Alzheimer's Disease Neuroimaging Initiative participants to investigate body mass index (BMI) trajectories preceding the progression from normal cognition to MCI (N‐t‐M progression), and to explore the association between brain pathology and BMI trajectories preceding incident MCI. Result: During N‐t‐M progression, participants developed multiple brain pathologies, and amyloid β (Aβ) accumulation in the frontotemporal region at baseline was associated with decreased BMI (Figure 1, false discovery rate‐corrected p<0.05). For pathological changes, participants had increased accumulation of Aβ and tau, accelerated hypometabolism, and decreased gray matter volume in the brain during N‐t‐M progression. More importantly, accelerated hypometabolism (p<0.001) and gray matter atrophy (p = 0.011) were associated with a rapid decline in BMI during N‐t‐M progression. Conclusion: These findings highlight the importance of regular monitoring of weight changes in older adults as faster BMI decline and lower BMI may be the result of brain pathology and associated with rapid progression of pathology, and provide a theoretical basis for strategies to minimize weight loss to prevent or delay MCI onset. [ABSTRACT FROM AUTHOR]

Facing considerable challenges associated with aging and dementia, China urgently needs an evidence‐based health‐care system for prevention and management of dementia. The Beijing Aging Brain Rejuvenation Initiative (BABRI) is a community‐based cohort study initiated in 2008 that focuses on asymptomatic stages of dementia, aims to develop community‐based prevention strategies for cognitive impairment, and provides a platform for scientific research and clinical trials. Thus far, BABRI has recruited 10,255 participants (aged 50 and over, 60.3% female), 2021 of whom have been followed up at least once at a 2‐ or 3‐year interval. This article presents aims and study design of BABRI; summarizes preliminary behavioral and neuroimaging findings on mild cognitive impairment (MCI) and results of clinical trials on MCI; and discusses issues concerning early prevention in community, MCI diagnosis methods, and applications of database of aging and dementia. BABRI is proposed to build a systematic framework on brain health in old age. [ABSTRACT FROM AUTHOR]

Background: Dysfunction of the thalamus has been proposed as a core mechanism of fatal familial insomnia. However, detailed metabolic and structural alterations in thalamic subnuclei are not well documented. We aimed to address the multimodal structuro‐metabolic pattern at the level of the thalamic nuclei in fatal familial insomnia patients, and investigated the clinical presentation of primary thalamic alterations. Method: Five fatal familial insomnia patients and 10 healthy controls were enrolled in this study. All participants underwent neuropsychological assessments, polysomnography, electroencephalogram, and cerebrospinal fluid tests. MRI and fluorodeoxyglucose PET were acquired on a hybrid PET/MRI system. Structural and metabolic changes were compared using voxel‐based morphometry analyses and standardized uptake value ratio analyses, focusing on thalamic subnuclei region of interest analyses. Correlation analysis was conducted between gray matter volume and metabolic decrease ratios, and clinical features. Result: The whole‐brain analysis showed that gray matter volume decline was confined to the bilateral thalamus and right middle temporal pole in fatal familial insomnia patients, whereas hypometabolism was observed in the bilateral thalamus, basal ganglia, and widespread cortices, mainly in the forebrain. In the regions of interest analysis, gray matter volume and metabolism decreases were prominent in bilateral medial dorsal nuclei, anterior nuclei, and the pulvinar, which is consistent with neuropathological and clinical findings. A positive correlation was found between gray matter volume and metabolic decrease ratios. Conclusion: Our study revealed specific structuro‐metabolic pattern of fatal familial insomnia that demonstrated the essential roles of medial dorsal nuclei, anterior nuclei, and pulvinar, which may be a potential biomarker in diagnosis. Also, primary thalamic subnuclei alterations may be correlated with insomnia, neuropsychiatric, and autonomic symptoms sparing primary cortical involvement. [ABSTRACT FROM AUTHOR]

Abstract: Exploring how risk genes cumulatively impair brain function in preclinical phase (i.e., in cognitively normal elderly) could provide critical insights into the pathophysiology of Alzheimer's disease (AD). Working memory impairment has always been a considerable cognitive deficit in AD, which is likely under complex genetic control. Though, the APOE ɛ4 allele could damage the working memory performance in normal elderly, dissociable results have been reported. This allele may exert specific effects in contexts with other genetic variants. The rs2618516 in the spondin 1 gene (SPON1) has been associated with AD risk and brain structure in the elderly. SPON1 may interact with APOE through processing the amyloid precursor protein and suppressing amyloid‐β levels. Using neuropsychological tasks from 710 individuals, we found significant SPON1 × APOE genotype interactions in working memory and executive function performances. Moreover, such interaction was also found in regional brain activations based on functional magnetic resonance imaging data with the n‐back working memory task performed in a sub‐cohort of 64 subjects. The effects of ɛ4 allele on activation of right inferior frontal gyrus, triangular part (IFGtriang.R) were modulated by rs2618516 in a working memory task. Furthermore, lower IFGtriang.R activation was associated with better cognitive functions. Moreover, the IFGtriang.R activation could mediate the impacts of SPON1 × APOE interactions on working memory performance. These findings suggested the importance of weighing APOE effects on brain activation under the working memory task within the context of the SPON1 genotype. [ABSTRACT FROM AUTHOR]

Neurodegenerative diseases such as Alzheimer's disease (AD) have been recognized to exhibit disease-specific brain vulnerability patterns. Apolipoprotein E ( APOE) ɛ4 allele imparts a high genetic risk of developing AD. Whether the APOE ɛ4 allele damages the brain when cognitive functions are still intact is important to understand, especially for possible early detection and intervention. This study aimed to examine the selective degeneration pattern associated with the APOE ɛ4 allele in the brains of cognitively normal elderly subjects. We enrolled 35 cognitively healthy ɛ4 carriers and 40 non-carriers (53 to 81 years old) to evaluate group differences in cortical thickness and brain activation during a memory-encoding task. We also assessed the functional connectivity of the brain regions with both structural and functional damages. The results from the neuropsychological tests showed that the performances of ɛ4 carriers and non-carriers were comparable. Primarily, we found that the precuneus exhibited thinner cortical thickness and decreased deactivation during memory encoding. Furthermore, the connectivity analyses show that carriers exhibited damaged connectivity of the precuneus to several regions in the default mode network and the attention/executive control network. Our study reveals the degeneration pattern of the ɛ4 allele, which could be used as a potential biomarker for early detection for possible interventions and treatments. Hum Brain Mapp 38:271-282, 2017. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The polymorphism of the Apolipoprotein E (APOE) promoter rs405509 can regulate the transcriptional activity of the APOE gene and is related to Alzheimer's disease (AD). However, its effects on cognitive performance and the underlying brain mechanisms remain unknown. Here, we performed a battery of neuropsychological tests in a large sample (837 subjects) of nondemented elderly Chinese people, and explored the related brain mechanisms via the construction of diffusion MRI-based structural connectome and graph analysis from a subset (84 subjects) of the sample. Cognitively, the rs405509 risk allele (TT) carriers showed decreased attention and execution functions compared with noncarriers (GG/GT). Regarding the topological alterations of the brain connectome, the risk allele group exhibited reduced global and local efficiency of white matter structural networks, mainly in the left anterior and posterior cingulate cortices (PCC). Importantly, the efficiency of the left PCC is correlated with the impaired attention function and mediates the impacts of the rs405509 genotype on attention. These results demonstrated that the rs405509 polymorphism affects attention function in nondemented elderly people, possibly by modulating brain structural connectivity of the PCC. This polymorphism may help us to understand the neural mechanisms of cognitive aging and to serve as a potential marker assessing the risk of AD. [ABSTRACT FROM AUTHOR]

Objectives To estimate the prevalence of mild cognitive impairment ( MCI) in Beijing, China, and to explore the potential protective and risk factors for MCI. Design Population-based survey. Setting The Beijing Ageing Brain Rejuvenation Initiative ( BABRI). Participants Participants randomly recruited from BABRI (N = 1,211). Measurements Participants underwent a battery of neuropsychological examinations to determine cognitive function and answered a series of personal questions. The prevalence of MCI and its subtypes were computed using Petersen's criteria. Influencing factors for MCI were estimated based on participant medical history, lifestyle, diet, and leisure activities. Results One thousand twenty (aged >55, mean 63.9 ± 6.6; 36.7% male) subjects completed the neuropsychological tests. The overall prevalence of MCI was 15.7%, with single-domain amnestic, multiple-domain amnestic, and nonamnestic subtype prevalences of 6.4%, 3.7%, and 5.6%, respectively. Eight hundred sixty-four subjects were used for the case-control analysis. Hypertension, diabetes mellitus, and cerebrovascular disease were found to be associated with MCI. Healthy diet and greater involvement in physical, intellectual, and social activities were associated with a lower risk of MCI. Conclusion The prevalence of MCI was compatible with that found in previous published reports, and the information on the epidemiology of MCI, especially risk factors, may help to explore therapeutic strategies and preventive approaches to delay conversion to dementia. [ABSTRACT FROM AUTHOR]