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Background: Understanding the pathological characteristics of various mild cognitive impairment (MCI) subtypes is crucial for the differential diagnosis of dementia. The purpose of this study was to feature divergent symptom-deficit profiles in amnestic MCI (aMCI) and non-amnestic MCI (naMCI)., Methods: T1 and DTI MRI data from a total of 158 older adults with 50 normal controls, 56 aMCI, and 52 naMCI were included. The voxel-wise gray matter volumes and the number of seed-based white matter fiber bundles were compared among these three groups. Furthermore, correlation and mediation analyses between the neuroimaging indices and cognitive measures were performed., Results: The aMCI with specific memory abnormalities was characterized by volumetric atrophy of the left hippocampus but not by damage in the linked white matter fiber bundles. Conversely, naMCI was characterized by both the altered volume of the right inferior frontal gyrus and the significant damage to fiber bundles traversing the region in all three directions, not only affecting fibers around the atrophied area but also distant fibers. Mediation analyses of gray matter-white matter-cognition showed that gray matter atrophy affects the number of fiber bundles and further affects attention and executive function. Meanwhile, fiber bundle damage also affects gray matter volume, which further affects visual processing and language., Conclusions: The divergent structural damage patterns of the MCI subtypes and cognitive dysfunctions highlight the importance of detailed differential diagnoses in the early stages of pathological neurodegenerative diseases to deepen the understanding of dementia subtypes and inform targeted early clinical interventions., (© 2023. The Author(s).)

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., (© 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

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., (© 2022. The Author(s).)

Background: Lobar cerebral microbleeds (CMBs), which can impair white matter (WM), are often concomitant with definite Alzheimer's disease (AD)., Objective: To explore the features of cognitive impairments and WM disruptions due to lobar CMBs in patients with AD., Methods: There were 310 participants who underwent Florbetapir F18 (AV45) amyloid PET and susceptibility-weighted imaging. Participants with cognitive impairment and amyloid-β positive (ADCI) were included into three groups: ADCI without CMBs, with strictly lobar CMBs (SL-CMBs), and with mixed CMBs (M-CMBs). Tract-based spatial statistics were performed to detect the group differences in WM integrity., Results: There were 82 patients and 29 healthy controls finally included. A decreasing tendency in memory and executive performance can be found among HCs > no CMBs (n = 16) >SL-CMBs (n = 41) >M-CMBs (n = 25) group. Compared to no CMBs, M-CMBs group had significantly decreased fractional anisotropy in left anterior thalamic radiation (ATR), forceps major, forceps minor and inferior longitudinal fasciculus, bilateral inferior fronto-occipital fasciculus (IFOF), and superior longitudinal fasciculus. M-CMBs group also had lower fractional anisotropy in left ATR, IFOF, uncinate fasciculus, and forceps minor compared with SL-CMBs. Furthermore, analysis of Pearson correlation indicated damages in discrepant WMs were positively associated with impairment of memory, executive function, and attention., Conclusion: This study showed lobar CMBs had intensively aggravated cognitive impairments associated with extensive WM damages in definite AD. These findings highlight that lobar CMBs play an important role in AD progression and need to be taken into consideration for the early detection of AD.

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., (© 2021 European Academy of Neurology.)

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., (© 2021 the Alzheimer's Association.)

White matter hyperintensity (WMH) is a common finding in aging population and considered to be a contributor to cognitive decline. Our study aimed to characterize the spatial patterns of WMH in different severities and explore its impact on cognition and brain microstructure in non-demented elderly. Lesions were both qualitatively (Fazekas scale) and quantitatively assessed among 321 community-dwelled individuals with MRI scanning. Voxel- and atlas-based analyses of the whole-brain white matter microstructure were performed. The WMH of the same severities was found to occur uniformly with a specific pattern of lesions. The severity of WMH had a significant negative association with the performance of working and episodic memory, beginning to appear in Fazekas 3 and 4. The white matter tracts presented significant impairments in Fazekas 3, which showed brain-wide changes above Fazekas 4. Lower FA in the superior cerebellar peduncle and left posterior thalamic radiation was mainly associated with episodic memory, and the middle cerebellar peduncle was significantly associated with working memory. These results support that memory is the primary domain to be affected by WMH, and the effect may potentially be influenced by tract-specific WM abnormalities. Fazekas scale 3 might be the critical stage predicting a future decline in cognition.

Advanced age and apolipoprotein E ( APOE ) ε4 allele are both associated with increased risk of the Alzheimer's disease (AD). However, the extent of the joint contribution of APOE ε4 allele and age on the brain white matter integrity, cognition and their relationship are unclear. We assessed the age-related variation differences of major cognitions in 846 non-demented elderly, and brain major white matter tracts in an MRI sub-cohort of 111 individuals between ε4 carriers and noncarriers. We found that: (i) carriers showed a steeper age-related decline after age 50 in general mental status, attention, language, and executive function and performed worse than noncarriers at almost all ages; (ii) main effect of age on anterior fibers, but main effect of APOE ε 4 on posterior fibers, and the interactive effect of them existed on anterior and posterior fibers; (iii) carriers showed an accelerated age-related integrity reduction of these fibers compared to noncarriers who had a slight decrease but not significant; and (iv) significant associations of the higher white matter integrity with better multi-cognitive performance in old ε4 carriers. Overall, combining APOE status with age may be useful in assessing possible mechanisms of disease development in AD.

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., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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.

The ε4 allele of the apolipoprotein E (APOE) gene and mild cognitive impairment (MCI) are both risk factors for Alzheimer's disease (AD). One factor is genetic, and the other is a developed condition during the aging process. The current study intended to discover the interactions of these two factors, which may be useful in the construction of a sensitive biomarker for early identification and intervention. Eight hundred eighty-five Chinese Han ethnic subjects (aged 55 and older) completed neuropsychological tests and APOE genotyping. One hundred ten of these participants underwent magnetic resonance imaging (MRI) for T1 structural and diffusion tensor imaging scans. Subjects were divided into four groups according to APOE ε4 carrying status and MCI condition: ε4+ MCI, ε4+ normal cognition (NC), ε4- MCI, and ε4- NC. In the studied Han population in Beijing, 16.9 % (ε2ε4 = 1.1 %, ε3ε4 = 14.8 %, and ε4ε4 = 0.9 %) carried at least one ε4 allele. Significant interactions between APOE ε4 and MCI were found in general cognitive function (p = 0.001) and white matter connectivity network (clustering coefficient, p = 0.004, and local efficiency, p = 0.011); the combination of ε4 positivity and MCI was accompanied by reductions in Mini-Mental Status Examination (MMSE) scores, global white matter network connectivity, and the right hippocampus (rHIP) nodal efficiency within that network (false discovery rate (FDR), p < 0.05). Our results suggest the presence of a genetic risk and MCI led to more severe pathological symptoms and could be informative in the implementation of clinical trials for early stages of AD.

The alteration of the default mode network (DMN) functional connectivity (FC) has been reported in patients with amnestic mild cognitive impairment (aMCI) as a predictor of Alzheimer's disease (AD). However, no studies exist that examined stage-dependent DMN FC changes throughout the course of aMCI. The present study aims to characterize patterns of DMN FC over three aMCI stages as first defined. Utilizing the extreme groups approach on the performance of memory tasks, aMCI subjects were divided into mild, moderate, and severe stages. Independent component analysis was used to assess DMN for individual patients in each of the three cross-sectionally defined stages. Instead of finding that continued monotonic decline was the case for the hippocampus volume, which we also investigated in this study, we observed an increase in DMN functional connectivity from mild aMCI to moderate aMCI and a decrease to severe aMCI, mainly in the left precuneus and superior parietal lobe. Moreover, the FC was significantly associated with cognitive performance. Though a longitudinal study is needed to confirm these results, our cross-sectional finding is that non-linear FC changes in DMN could be a characteristic of prodromal early disease development.

Background: As a risk factor for Alzheimer's disease (AD), type 2 diabetes mellitus (T2DM) itself causes cognitive impairment and has higher prevalence of mild cognitive impairment (MCI)., Objective: The aim of this study was to explore the cognition especially the episodic memory difference, the DMN functional connectivity and DMN-related white matter integrity in patients with both T2DM and amnestic MCI (T2DM-MCI) as compared to patients with T2DM only., Methods: Focusing especially on T2DM population, we investigated the default mode network (DMN) through resting-state functional magnetic resonance imaging among 22 elderly T2DM-MCI patients and 24 elderly T2DM patients. Including primarily the bilateral cingulum, hippocampus and uncinate fasciculus, these DMN white matter fibers were also closely associated with episodic memory and the integrity of them was also investigated using diffusion tensor imaging in 19 elderly T2DM-MCI patients and 23 elderly T2DM patients., Results: Compared with the patients with T2DM, the T2DM-MCI patients performed worse in several areas of cognition besides episodic memory, and showed stronger DMN functional connectivity in the left precuneus and weaker functional connectivity in the left calcarine, as well as decreased integrity of the left cingulate bundle and bilateral uncinate fasciculus. Furthermore, a correlation analysis indicated that higher left calcarine connectivity was associated with better episodic memory performance among the overall group., Conclusion: Our results demonstrated that T2DM patients with comorbid amnestic MCI had abnormal functional connectivity patterns and decreased white matter integrity, which could potentially serve as AD or AD risk biomarkers for early detection of those elderly individuals with T2DM., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Aims: Episodic memory depends on the maintenance of an intact default mode network (DMN), and is one of the earliest cognitive domains to become impaired in type 2 diabetes mellitus (T2DM). Therefore, exploring the alterations in task-related DMN deactivation and functional connectivity that affect episodic memory in T2DM will help to enhance our understanding of the allocation patterns underlying memory function in T2DM., Methods: The current study assessed changes in DMN activation and architecture during the encoding of a functional magnetic resonance imaging task in 39 patients with T2DM and 41 healthy controls which were recruited from local communities in Beijing, China., Results: We found that patients with T2DM and intact episodic memory performance exhibited reduced deactivation in the right precuneus and the middle temporal gyrus during the episodic memory task. Furthermore, an anterior-posterior disconnection phenotype and altered topological configuration of the DMN were observed in patients with T2DM using graph-theoretical approaches. Correlation analysis showed that altered deactivation during the episodic memory task was closely related to connectivity dysfunction and topological properties in the DMN., Conclusions: Our findings demonstrate that the maintenance of memory in patients with T2DM involves reduced deactivation and impaired anterior-posterior connections in the DMN during encoding., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Type 2 diabetes mellitus is accompanied by cognitive impairment and is associated with an increased risk of dementia. Damage to brain structures such as white matter network disruption may underlie this cognitive disturbance. In the present study, 886 non-diabetic and 163 type 2 diabetic participants completed a battery of neuropsychological tests. Among them, 38 diabetic patients and 34 non-diabetic participants that matched the patients for age/sex/education received a magnetic resonance imaging-based diffusion tensor imaging. Then we calculated the topological properties of the white matter network using a graph theoretical method to investigate network efficiency differences between groups. We found that type 2 diabetic patients had inferior performances compared to the non-diabetic controls, in several cognitive domains involving executive function, spatial processing, memory, and attention. We also found that diabetic patients exhibited a disrupted topological organization of the white matter network (including the global network properties, i.e., network strength, global efficiency, local efficiency and shortest path length, and the nodal efficiency of the right rolandic operculum) in the brain. Moreover, those global network properties and the nodal efficiency of the right rolandic operculum both had positive correlations with executive function in the patient group. The results suggest that type 2 diabetes mellitus leads to an alteration in the topological organization of the cortical white matter network and this alteration may account for the observed cognitive decline.

Previous studies have demonstrated that Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI) exhibited anatomical and functional abnormalities in the anterior cingulate cortex (ACC) and accumulating evidence supported the hypothesis that changes in the ACC predict the progression from aMCI to AD. In this study, we aimed to explore how the two functional and structural heterogeneous sub-regions of ACC, namely the dorsal ACC (dACC) and the ventral ACC (vACC), changed in aMCI and whether the structural connectivity affects the functional connectivity between the two ACC subregions. To investigate this hypothesis, we studied resting-state fMRI and DTI images in a group of 24 aMCIs and 29 healthy controls. The dACC exhibited a significantly increased functional connectivity in the Salience Network (SN) and a decreased functional connectivity with the vACC in aMCI. The DTI results showed that the bilateral cingulum fibers were the most damaged tracts in aMCI and that the fractional anisotrophy of the left anterior cingulum was significantly correlated with the functional connectivity between the two ACC sub-regions. In conclusion, this study revealed the pathological changes in the intrinsic functional connectivity of the ACC within SN, as well as the connectivity between the dACC and vACC in aMCI. Our study also revealed that disrupted white matter integrity of the anterior regions of the cingulum was associated with the alterations in subregional connectivity in the ACC.

Objective: Type 2 diabetes mellitus (T2DM) has important effects on cognition and the risk for Alzheimer disease (AD). Working memory (WM) is a susceptible cognitive domain of mild cognitive impairment and AD. Thus, the identification of brain activation patterns under different WM loads can potentially enhance our understanding of the mechanisms underlying cognitive dysfunction in T2DM., Research Design and Methods: The current study assessed the effects of T2DM on cognitive performance and explored the related neuronal damage through a visual n-back task and functional magnetic resonance imaging., Results: We found that patients with T2DM exhibited worse executive and memory abilities than control subjects. Furthermore, the patterns of brain activation changed under different WM loads in the T2DM patients, who exhibited reduced activation in the left inferior frontal gyrus under low loads and reduced activation in the left middle frontal gyrus and superior frontal gyrus (SFG) under high loads. Thus, more regions of diminished activation were seen in the frontal cortex with increasing task difficulty. Furthermore, we found that lower SFG activation was associated with worse cognitive function., Conclusions: The findings demonstrate deficient WM in patients with T2DM and the relation between cognitive function and degree of neuronal activity and their relevance to AD risk. Further longitudinal studies are needed to replicate these results and to evaluate the clinical value of brain imaging methods in the prediction of disease progress in these patients., (© 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Background: Various amnestic mild cognitive impairment (aMCI) subtypes have been identified as single domain (SD) or multiple domain (MD), with differential probabilities of progression to Alzheimer disease (AD). Detecting the differences in the alterations in gray matter (GM) and intrinsic brain activity between the subtypes of aMCI help to understand their pathophysiological mechanisms and was conducive to construct such potential biomarkers to monitor the progression of aMCI., Methods: In all, 22 normal controls (NCs), 18 patients with SD-aMCI, and 17 patients with MD-aMCI participated in the study. The amplitude of low-frequency fluctuations (ALFFs) during rest represented intrinsic brain activity. Voxel-based morphometry analysis was used to measure the GM volume., Results: The MD-aMCI showed reduced GM in hippocampus (Hip), parahippocampal gyrus (PHG), and other regions than SD-aMCI. The SD-aMCI had reduced GM only in Hip and PHG than in NC. The MD-aMCI showed decreased ALFF in posterior cingulate cortex (PCC) and precuneus and increased ALFF in anterior cingulate cortex (ACC), PHG, and Hip compared with both SD-aMCI and NC. However, no ALFF difference was found between SD-aMCI and NC. Neuropsychological measures were correlated with ALFF in PCC and ACC only in the MD-aMCI., Conclusions: Patients with MD-aMCI displayed more severe GM atrophy and ALFF changes than patients with SD-aMCI. The results suggested that aMCI is heterogeneous and that MD-aMCI may be a prodromal stage which is more close to AD., (© The Author(s) 2014.)

Objective: To investigate effects and functional mechanism of compound Congrongyizhi Capsule (CCRC), a Chinese medicine, on cognitive functions against amnestic mild cognitive impairment (aMCI) patients with functional magnetic resonance imaging (fMRI) based on n-back task., Methods: Forty-one aMCI participants from hospital and local communities in Beijing and randomly divided into treatment (16 patients with CCRC capsule treatment), placebo (12 patients with placebo capsules) and control group (13 patients with no treatment). The duration of intervention lasted for 3 months. Neuropsychological tests and fMRI were applied to assess cognitive ability and brain activation changes after three months treatment., Results: Drug group (n=16) presented increased significance in the MMSE (P=0.008) and digit span (P<0.001) tests, while other scores of neuropsychological tests showed no statistical significance. fMRI results showed an increased brain negative activation in drug group during performing the n-back working-memory task in posterior cingulate (PCC), inferior frontal gyrus and lingual gyrus regions after 3 months; placebo and control group did not show the same effect. Meanwhile, there were negative correlations between left PCC activation levels and changed values of MMSE and digit span separately since increased negative activation was associated with better performance on the scores of MMSE and Digit Span tests., Conclusions: CCRC can increase negative activation degree of PCC under performing working memory tasks while this modulation are associated with better performance on the MMSE and Digit Span.

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., (© 2013, Copyright the Authors Journal compilation © 2013, The American Geriatrics Society.)

Patients with amnestic mild cognitive impairment (aMCI) often display deficits in episodic memory. Amnestic MCI is now recognized as a prodromal form of Alzheimer's disease. Various aMCI clinical subtypes have been identified as ingle-domain (SD) or multi-domain (MD). The various subtypes represent heterogeneous syndrome indicating the probability of progression to AD, impaired cognitive domains and so on. To examine the characteristics of brain regions of aMCI subtypes is likely to be important for early diagnosis and prediction to AD. This study investigated brain functional activation and hippocampal atrophy during a visually complex scene encoding in 20 individuals with aMCI-SD, 14 individuals with aMCI-MD and 25 healthy controls. During the encoding task, aMCI-MD patients had reduced activation in right superior medial frontal, right inferior and middle temporal, right middle occipital and left inferior frontal regions compared to controls. The different active brain regions between aMCI-MD and aMCI-SD patients are the right middle occipital and left middle cingulum regions. The aMCI-MD group had significantly lower left hippocampus volumes compared to the aMCI-SD group and controls, but there was no difference between aMCI-SD patients and the control group in terms of left hippocampus atrophy. The findings provide evidence that aMCI may represent a heterogeneous group. The aMCI-MD patients displayed more severe hippocampcal atrophy and fMRI activation changes than aMCI-SD. The aMCIMD may represent a more advanced prodromal stage of AD.