Cortical thickness reveals sex differences in verbal and visuospatial memory.

Although previous studies have reported the sex differences in behavior/cognition and the brain, the sex difference in the relationship between memory abilities and the underlying neural basis in the aging process remains unclear. In this study, we used a machine learning model to estimate the association between cortical thickness and verbal/visuospatial memory in females and males and then explored the sex difference of these associations based on a community-elderly cohort (n = 1153, age ranged from 50.42 to 86.67 years). We validated that females outperformed males in verbal memory, while males outperformed females in visuospatial memory. The key regions related to verbal memory in females include the medial temporal cortex, orbitofrontal cortex, and some regions around the insula. Further, those regions are more located in limbic, dorsal attention, and default-model networks, and are associated with face recognition and perception. The key regions related to visuospatial memory include the lateral prefrontal cortex, anterior cingulate gyrus, and some occipital regions. They overlapped more with dorsal attention, frontoparietal and visual networks, and were associated with object recognition. These findings imply the memory performance advantage of females and males might be related to the different memory processing tendencies and their associated network.

Lesion Network Mapping for Neurological Deficit in Acute Ischemic Stroke.

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.

The characteristics of glucose metabolism and functional connectivity in posterior default network during nondemented aging: relationship with executive function performance.

BACKGROUND: Understanding the characteristics of intrinsic connectivity networks (ICNs) in terms of both glucose metabolism and functional connectivity (FC) is important for revealing cognitive aging and neurodegeneration, but the relationships between these two aspects during aging has not been well established in older adults. OBJECTIVE: This study is to assess the relationship between age-related glucose metabolism and FC in key ICNs, and their direct or indirect effects on cognitive deficits in older adults. METHODS: We estimated the individual-level standard uptake value ratio (SUVr) and FC of eleven ICNs in 59 cognitively unimpaired older adults, then analyzed the associations of SUVr and FC of each ICN and their relationships with cognitive performance. RESULTS: The results showed both the SUVr and FC in the posterior default mode network (pDMN) had a significant decline with age, and the association between them was also significant. Moreover, both decline of metabolism and FC in the pDMN were significantly correlated with executive function decline. Finally, mediation analysis revealed the glucose metabolism mediated the FC decline with age and FC mediated the executive function deficits. CONCLUSIONS: Our findings indicated that covariance between glucose metabolism and FC in the pDMN is one of the main routes that contributes to age-related executive function decline.

The association between household and family composition and mental health of the elderly: mediating role of lifestyle.

BACKGROUND: Mental health in the elderly has multiple determinants, and studies indicate household and family composition, economic status, and family support are key factors. However, these are difficult to modify, and better lifestyle for the elderly can be a possible intervention. The current study examined the mediating role of lifestyle in the association between these three types of the household and family composition (living alone, living with a spouse, and living with children) and mental health in older adults. METHODS: We studied 5,407 participants (58.7% female, age 45 + years) from the Beijing Aging Brain Rejuvenation Initiative Project. All participants underwent a battery of examinations to measure degree loneliness, depression, and global cognitive function. We also surveyed personal lifestyles. We used a mediation analysis to determine the relative contribution of each lifestyle factor on mental health outcomes. RESULTS: Older adults living alone rarely participated in mental and social activities and often had irregular diets; those adults living with children spent most of their time caring for grandchildren and had irregular eating and sleeping schedules; those living with a spouse often engaged in a variety of leisure activities and had the best life habits. Mediation analyses showed that dietary and sleeping irregularity partially mediated the negative effects of living alone on mental health, and were moderated by age and gender. CONCLUSIONS: Living with a spouse was associated with benefits for the mental health of middle-aged and older adults (especially older and female individuals), through modifying better lifestyles than those of individuals with the other two types of the household and family composition.

From local properties to brain-wide organization: A review of intraregional temporal features in functional magnetic resonance imaging data.

Based on the fluctuations ensembled over neighbouring neurons, blood oxygen level-dependent (BOLD) signal is a mesoscale measurement of brain signals. Intraregional temporal features (IRTFs) of BOLD signal, extracted from regional neural activities, are utilized to investigate how the brain functions in local brain areas. This literature highlights four types of IRTFs and their representative calculations including variability in the temporal domain, variability in the frequency domain, entropy, and intrinsic neural timescales, which are tightly related to cognitions. In the brain-wide spatial organization, these brain features generally organized into two spatial hierarchies, reflecting structural constraints of regional dynamics and hierarchical functional processing workflow in brain. Meanwhile, the spatial organization gives rise to the link between neuronal properties and cognitive performance. Disrupted or unbalanced spatial conditions of IRTFs emerge with suboptimal cognitive states, which improved our understanding of the aging process and/or neuropathology of brain disease. This review concludes that IRTFs are important properties of the brain functional system and IRTFs should be considered in a brain-wide manner.

Tau as a biomarker of cognitive impairment and neuropsychiatric symptom in Alzheimer's disease.

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, Aß, 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, Aß, 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 Aß were unique and the regions affected by hypometabolism were widely distributed. Unlike Aß, 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 Aß. Finally, hypometabolism and tau had higher accuracy in differentiating the AD patients from controls (accuracy = 0.88, accuracy = 0.85) than Aß (accuracy = 0.81), and the combined three were the highest (accuracy = 0.95). These findings suggest tau pathology is superior over Aß 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.

Brain Network Organization and Aging.

Despite recent substantial progress in neuroscience, the mechanisms and principles of the complex structure, functions, and the relationship between the brain and cognitive functions have not been fully understood. The modeling method of brain network can provide a new perspective for neuroscience research, and it is possible to provide new solutions to the related research problems. On this basis, the researchers define the concept of human brain connectome to highlight and emphasize the importance of network modeling methods in neuroscience. For example, using diffusion-weighted magnetic resonance imaging (dMRI) technology and fiber tractography methods, a white matter connection network of the whole brain can be constructed. From the perspective of brain function, functional magnetic resonance imaging (fMRI) data can build the brain functional connection network. A structural covariation modeling method is used to obtain a brain structure covariation network, and it appears to reflect developmental coordination or synchronized maturation between areas of the brain. In addition, network modeling and analysis methods can also be applied to other types of image data, such as positron emission tomography (PET), electroencephalogram (EEG), and magnetoencephalography (MEG). This chapter mainly reviews the research progress of researchers on brain structure, function, and other aspects at the network level in recent years.

The Aging Patterns of Brain Structure, Function, and Energy Metabolism.

The normal aging process brings changes in brain structure, function, and energy metabolism, which are presumed to contribute to the age-related decline in brain function and cognitive ability. This chapter aims to summarize the aging patterns of brain structure, function, and energy metabolism to distinguish them from the pathological changes associated with neurodegenerative diseases and explore protective factors in aging. We first described the normal atrophy pattern of cortical gray matter with age, which is negatively affected by some neurodegenerative diseases and is protected by a healthy lifestyle, such as physical exercise. Next, we summarized the main types of age-related white matter lesions, including white matter atrophy and hyperintensity. Age-related white matter changes mainly occurred in the frontal lobe, and white matter lesions in posterior regions may be an early sign of Alzheimer's disease. In addition, the relationship between brain activity and various cognitive functions during aging was discussed based on electroencephalography, magnetoencephalogram, and functional magnetic resonance imaging. An age-related reduction in occipital activity is coupled with increased frontal activity, which supports the posterior-anterior shift in aging (PASA) theory. Finally, we discussed the relationship between amyloid-ß deposition and tau accumulation in the brain, as pathological manifestations of neurodegenerative disease and aging.

Sex Differences in Cortical Morphometry and White Matter Microstructure During Brain Aging and Their Relationships to Cognition.

Changes in brain structure are associated with aging, and accompanied by the gradual deterioration of cognitive functions, which manifests differently in males and females. Here, we quantify the age-related spatial aging patterns of brain gray and white matter structures, their volume reduction rate, their relationships with specific cognitive functions, as well as differences between males and females in a cross-sectional nondementia dataset. We found that both males and females showed extensive age-related decreases in the volumes of most gray matter and white matter regions. Females have larger regions where the volume decreases with age and a greater slope (females: 0.199%, males: 0.183%) of volume decrease in gray matter. For white matter, no significant sex differences were found in age-related regions, and the slope of volume decrease. More significant associations were identified between brain structures and cognition in males during aging than females. This study explored the age-related regional variations in gray matter and white matter, as well as the sex differences in a nondemented elderly population. This study helps to further understand the aging of the brain structure and sex differences in the aging of brain structures and provides new evidence for the aging of nondemented individuals.

Contributions of early-life cognitive reserve and late-life leisure activity to successful and pathological cognitive aging.

BACKGROUND: The identification of factors that specifically influence pathological and successful cognitive aging is a prerequisite for implementing disease prevention and promoting successful aging. However, multi-domain behavioral factors that characterize the difference between successful and pathological cognitive aging are not clear yet. METHODS: A group of community-dwelling older adults (N = 1347, aged 70-88 years) in Beijing was recruited in this cross-sectional study, and a sub-cohort was further divided into successful cognitive aging (SCA, N = 154), mild cognitive impairment (MCI, N = 256), and cognitively normal control (CNC, N = 173) groups. Analyses of variance, regression models with the Shapley value algorithm, and structural equation model (SEM) analyses were conducted to determine specific influencing factors and to evaluate their relative importance and interacting relationships in altering cognitive performance. RESULTS: We found that abundant early-life cognitive reserve (ECR, including the level of education and occupational attainment) and reduced late-life leisure activity (LLA, including mental, physical, and social activities) were distinct characteristics of SCA and MCI, respectively. The level of education, age, mental activity, and occupational attainment were the top four important factors that explained 31.6% of cognitive variability. By SEM analyses, we firstly found that LLA partially mediated the relationship between ECR and cognition; and further multi-group SEM analyses showed ECR played a more direct role in the SCA group than in the MCI group: in the SCA group, only the direct effect of ECR on cognition was significant, and in the MCI group, direct effects between ECR, LLA and cognition were all significant. CONCLUSIONS: Results of this large-sample community-based study suggest it is important for older adults to have an abundant ECR for SCA, and to keep a high level of LLA to prevent cognitive impairment. This study clarifies the important rankings of behavioral characteristics of cognitive aging, and the relationship that ECR has a long-lasting effect on LLA and finally on cognition, providing efficient guidance for older adults to improve their cognitive function and new evidence to explain the heterogeneity of cognitive aging.

Relationship between the disrupted topological efficiency of the structural brain connectome and glucose hypometabolism in normal aging.

Normal aging is accompanied by structural degeneration and glucose hypometabolism in the human brain. However, the relationship between structural network disconnections and hypometabolism in normal aging remains largely unknown. In the present study, by combining MRI and PET techniques, we investigated the metabolic mechanism of the structural brain connectome and its relationship with normal aging in a cross-sectional, community-based cohort of 42 cognitively normal elderly individuals aged 57-84 years. The structural connectome was constructed based on diffusion MRI tractography, and the network efficiency metrics were quantified using graph theory analyses. FDG-PET scanning was performed to evaluate the glucose metabolic level in the cortical regions of the individuals. The results of this study demonstrated that both network efficiency and cortical metabolism decrease with age (both p < 0.05). In the subregions of the bilateral thalamus, significant correlations between nodal efficiency and cortical metabolism could be observed across subjects. Individual-level analyses indicated that brain regions with higher nodal efficiency tend to exhibit higher metabolic levels, implying a tight coupling between nodal efficiency and glucose metabolism (r = 0.56, p = 1.15 × 10-21). Moreover, efficiency-metabolism coupling coefficient significantly increased with age (r = 0.44, p = 0.0046). Finally, the main findings were also reproducible in the ADNI dataset. Together, our results demonstrate a close coupling between structural brain connectivity and cortical metabolism in normal elderly individuals and provide new insight that improve the present understanding of the metabolic mechanisms of structural brain disconnections in normal aging.

Disrupted anterior and posterior hippocampal structural networks correlate impaired verbal memory and spatial memory in different subtypes of mild cognitive impairment.

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.

Accelerating Structural Degeneration in Temporal Regions and Their Effects on Cognition in Aging of MCI Patients.

Age is the major risk factor for Alzheimer's disease (AD) and for mild cognitive impairment (MCI). However, there is limited evidence about MCI-specific aging-related simultaneous changes of the brain structure and their impact on cognition. We analyzed the brain imaging data from 269 subjects (97 MCI patients and 172 cognitively normal [CN] elderly) using voxel-based morphometry and tract-based spatial statistics procedures to explore the special structural pattern during aging. We found that the patients with MCI showed accelerated age-related reductions in gray matter volume in the left planum temporale, thalamus, and posterior cingulate gyrus. The similar age×group interaction effect was found in the fractional anisotropy of the bilateral parahippocampal cingulum white matter tract, which connects the temporal regions. Importantly, the age-related temporal gray matter and white matter alterations were more significantly related to performance in memory and attention tasks in MCI patients. The accelerated degeneration patterns in the brain structure provide evidence for different neural mechanisms underlying aging in MCI patients. Temporal structural degeneration may serve as a potential imaging marker for distinguishing the progression of the preclinical AD stage from normal aging.

Age-Related Decline in the Topological Efficiency of the Brain Structural Connectome and Cognitive Aging.

Brain disconnection model has been proposed as a possible neural mechanism for cognitive aging. However, the relationship between structural connectivity degeneration and cognitive decline with normal aging remains unclear. In the present study, using diffusion MRI and tractography techniques, we report graph theory-based analyses of the brain structural connectome in a cross-sectional, community-based cohort of 633 cognitively healthy elderly individuals. Comprehensive neuropsychological assessment of the elderly subjects was performed. The association between age, brain structural connectome, and cognition across elderly individuals was examined. We found that the topological efficiency, modularity, and hub integration of the brain structural connectome exhibited a significant decline with normal aging, especially in the frontal, parietal, and superior temporal regions. Importantly, network efficiency was positively correlated with attention and executive function in elderly subjects and had a significant mediation effect on the age-related decline in these cognitive functions. Moreover, nodal efficiency of the brain structural connectome showed good performance for the prediction of attention and executive function in elderly individuals. Together, our findings revealed topological alterations of the brain structural connectome with normal aging, which provides possible structural substrates underlying cognitive aging and sensitive imaging markers for the individual prediction of cognitive functions in elderly subjects.

Early prevention of cognitive impairment in the community population: The Beijing Aging Brain Rejuvenation Initiative.

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.

The Contribution of Genetic Factors to Cognitive Impairment and Dementia: Apolipoprotein E Gene, Gene Interactions, and Polygenic Risk.

Alzheimer's disease (AD) is a progressive neurodegenerative disease. Although it has been studied for years, the pathogenesis of AD is still controversial. Genetic factors may play an important role in pathogenesis, with the apolipoprotein E (APOE) gene among the greatest risk factors for AD. In this review, we focus on the influence of genetic factors, including the APOE gene, the interaction between APOE and other genes, and the polygenic risk factors for cognitive function and dementia. The presence of the APOE ε4 allele is associated with increased AD risk and reduced age of AD onset. Accelerated cognitive decline and abnormal internal environment, structure, and function of the brain were also found in ε4 carriers. The effect of the APOE promoter on cognition and the brain was confirmed by some studies, but further investigation is still needed. We also describe the effects of the associations between APOE and other genetic risk factors on cognition and the brain that exhibit a complex gene⁻gene interaction, and we consider the importance of using a polygenic risk score to investigate the association between genetic variance and phenotype.

APOE influences working memory in non-demented elderly through an interaction with SPON1 rs2618516.

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-ß 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.

Precuneus degeneration in nondemented elderly individuals with APOE ɛ4: Evidence from structural and functional MRI analyses.

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.

The effects of an APOE promoter polymorphism on human cortical morphology during nondemented aging.

Apolipoprotein E (APOE) is the best-known susceptibility gene for AD. It has been well demonstrated that the ε4 allele of the APOE gene can affect brain structure/function in nondemented individuals; however, other polymorphisms in the APOE gene have been largely overlooked when assessing the effects of APOE on the neural system. Rs405509 is a newly recognized AD-related polymorphism located in the APOE promoter region that can regulate the transcriptional activity of the APOE gene. To date, it remains unknown whether and how this APOE promoter polymorphism affects the human brain in aging. Here, for the first time, we investigate the effects of the rs405509 genotype (T/T vs G-allele) on human cortical morphology using a large cohort of nondemented elderly subjects (120 subjects in total; aged 52- 81 years). High-resolution structural MRI was performed; cortical thickness and surface area were analyzed separately. Intriguingly, nondemented carriers of the rs405509 T/T genotype showed an accelerated age-related reduction of thickness in the left parahippocampal gyrus compared with the G-allele carriers. Furthermore, the cortical thickness covariance between the left parahippocampal gyrus and left medial cortex, including the left medial superior frontal gyrus, supplementary motor area, and paracentral lobule, was modulated by the interaction of the rs405509 genotype and age. These novel findings suggest an important role for the APOE promoter polymorphism in the human brain and also provide valuable insights into how the rs405509 genotype shapes the neural system to modulate the risk of developing AD.

Disrupted Frontoparietal Network Mediates White Matter Structure Dysfunction Associated with Cognitive Decline in Hypertension Patients.

Some previous reports have suggested that hypertension is a risk factor for dementia and cognitive impairments. Using behavioral data from 1007 elderly human subjects (405 hypertensive patients) of Han ethnicity from Beijing, China, the present study aimed to assess the effects of hypertension on cognitive performance and explore related neuronal changes via advanced resting-state functional magnetic resonance imaging and diffusion tensor imaging data from 84 of these subjects (44 hypertensive patients). Cognitively, we found that patients with hypertension showed decreased executive functions and attention compared with those with normotension in the large sample. In magnetic resonance imaging scan sample, using independent component analysis to examine the functional connectivity difference between the two groups, we found that the frontoparietal networks in the hypertensive group exhibited altered patterns compared with the control group, mainly in the inferior parietal lobe, left inferior frontal lobe, and precuneus. Using tract-based spatial statistics to investigate the between-group structural difference, we found that the hypertensive group showed significantly reduced integrity of white matter in the bilateral superior longitudinal fasciculus. Importantly, using the mediation analysis, we found that the functional connectivity of the frontoparietal networks mediates the impact of white matter on executive function in the hypertensive group. The results demonstrate that hypertension targets a specific pattern of cognitive decline, possibly due to deficits in the white matter and functional connectivity in frontal and parietal lobes. Our findings highlight the importance of brain protection in hypertension. SIGNIFICANCE STATEMENT: Hypertension is a risk factor for cognitive decline and dementia. However, the neural mechanism underlying cognitive decline in hypertension is largely unknown. We studied the relationship among cognitive decline, brain functional, and structural changes in hypertensive patients via advanced resting-state functional magnetic resonance imaging and diffusion tensor imaging data in a Chinese cohort. Hypertensive patients showed executive dysfunction, along with disrupted functional connectivity in frontoparietal (FP) networks and reduced integrity of white matter in the bilateral superior longitudinal fasciculus. Importantly, the functional connectivity changes mediate the impact of white matter alterations on cognitive decline in the hypertensive group. Our findings provide a better understanding of the mechanism of cognitive decline in hypertension and highlight the importance of brain protection in hypertension.