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Background Mutations in microtubule associated protein tau (MAPT), progranulin (GRN), chromosome 9 open-reading frame 72 (C9orf72) and CHCHD10 genes have been reported causing frontotemporal dementia (FTD) in different populations. However, collective analysis of mutations in these four genes in Chinese FTD patients has not been reported yet. Methods The aim of this study was to investigate the genetic features of Chinese patients with MAPT, GRN, C9orf72 or CHCHD10 gene mutations in an FTD cohort recruited from multi clinical centers in Shanghai metropolitan areas, China. MAPT, GRN and CHCHD10 genes were analysed by direct sequencing, and C9orf72 hexanucleotide repeat expansion was analysed by repeat-primed PCR in 82 patients with sporadic FTD. The identified gene variants were screened in 400 age matched controls. Results We found one known pathogenic variant (rs63750959) and one novel mutation (NG_007398.1: g.120962C>T; H299Y) of MAPT gene, one novel variant (c.750C>A; D250E) of GRN gene and two novel mutations in CHCHD10 gene (c.63C>T, no AA change; c.71G>A, P24L). No abnormal C9orf72 gene hexanucleotide repeat expansion was identified in this cohort. Collectively, genetic testing could discover 4.9% sporadic FTD patients with genetic causes. In addition, MAPT and CHCHD10 might be more important genes affecting Chinese with FTD.

The semantic system is a core component underlying many cognitive functions, and its deterioration can lead to various behavioral deficits. The Pyramids and Palm Trees Test (Howard & Patterson, 1992) and the Kissing and Dancing Test (Bak & Hodges, 2003) are among the most widely used semantic assessments, and they have been adapted into many languages and for many populations. We adapted these tests to the Mainland Chinese population by adopting culturally appropriate items and collecting normative data in healthy Chinese participants. In addition, accumulating research has shown that semantic representations have multidimensional structures that include various types of knowledge, and in the Pyramids and Palm Trees Test mainly evaluates associative relationships. Therefore, we developed additional tests to examine three other aspects of semantic knowledge: taxonomic, functional, and manipulative. We found significant correlations among all tests in healthy participants. Moreover, the level of education and age affected performance on the tests of associative relationships, taxonomic relationships, and manipulation similarity.

The verbal fluency test (VFT) can be dissociated into “clustering” (generating words within subcategories) and “switching” (shifting between clusters), which may be valuable in differential diagnosis. In the current study, we investigated the validity of VFT in the differential diagnosis of Alzheimer’s disease (AD, n = 65), vascular dementia (VaD, n = 65), mild cognitive impairment (MCI, n = 92), and vascular cognitive impairment without dementia (VCIND, n = 76) relative to cognitively normal senior controls (NC, n = 374). We found that in the NC group, the total correct score was significantly correlated with age and education; males generated more subcategories; cluster size increased with education, and subcategory and switching decreased with age. A significantly progressive advantage was observed in VFT scores in the sequence NC > MCI/VCIND > AD/VaD, and this significantly discriminated dementia patients from the other groups. AD patients performed better in all four VFT scores than VaD patients. Subcategory and switching scores significantly distinguished AD from VaD patients (AD > VaD; mean difference, 0.50 for subcategory, P

Objectives To evaluate the effectiveness of the Chinese version of the Montreal Cognitive Assessment Basic (MoCA-BC) as a screening tool for detecting mild cognitive impairment (MCI) in Chinese elderly adults. Design Cross-sectional. Setting Huashan Hospital, Shanghai, China. Participants Individuals with MCI (n = 264) and mild Alzheimer's disease (AD) (n = 160) were recruited from the Memory Clinic, Huashan Hospital; cognitively normal controls were recruited from Jinshan Community, Shanghai, China (n = 280). Measurements MoCA-BC scores. Results The MoCA-BC had good criterion-related validity (Pearson correlation coefficient MoCA-BC vs MMSE = 0.787) and reliable internal consistency (Cronbach alpha = 0.807). The optimal cutoff scores for MCI screening were 19 for individuals with no more than 6 years of education, 22 for individuals with 7 to 12 years of education, and 24 for individuals with more than 12 years of education. The MoCA-BC was superior to the MMSE for detecting MCI, with optimal sensitivity and specificity across all education groups using the above cutoff scores. Conclusion The MoCA-BC is a reliable cognitive screening test across all education levels in Chinese elderly adults, with high acceptance and good reliability.

Both the apolipoprotein E (APOE) ɛ4 allele and amnestic mild cognitive impairment (aMCI) are considered to be risk factors for Alzheimer's disease (AD). The primary aim of this study was to determine whether the aMCI-related abnormality in gray matter (GM) cortical thickness and white matter (WM) tracts integrity would be modified by the APOE genotype. A total of 146 older adults, including 64 aMCI patients (28 ɛ4 carriers and 36 non-carriers) and 82 healthy controls (39 ɛ4 carriers and 43 non-carriers), underwent a standardized clinical interview, neuropsychological battery assessment, and multi-modal brain magnetic resonance imaging scans. Compared with control subjects, the patients with aMCI showed significantly reduced cortical thickness bilaterally in the parahippocampal gyrus and disrupted WM integrity in the limbic tracts (e.g., increased mean diffusivity in the right parahippocampal cingulum and bilateral uncinate fasciculus). However, no significant main effects of the APOE genotype and diagnosis-by-genotype interaction on GM thickness and WM integrity were observed. Further, diffusivity measures of the limbic WM tracts were significantly correlated with the parahippocampal atrophy in aMCI. Importantly, the parahippocampal thickness and diffusivity measures of the limbic WM tracts were significantly correlated with the cognitive performance (i.e., episodic memory Z score) in patients with aMCI. These results demonstrate that WM microstructural disruptions in the limbic tracts are present at the early stage of AD in an APOE-independent manner; and this degeneration may occur progressively, in parallel with parahippocampal atrophy, and may specifically contribute to early initial impairment in episodic memory.

Background The present study was conducted to detect neuropsychological differences and to identify discriminators between mild dementia with L ewy bodies (DLB ) and mild A lzheimer's disease (AD ). Methods The present study included 37 mild DLB patients, 48 mild AD patients, and 80 healthy elderly individuals. A comprehensive battery of neuropsychological tests was administrated to assess their cognitive function. Linear stepwise discriminant analysis was used to identify the neuropsychological measures with values that could differentiate between mild DLB and mild AD . Results The mild DLB group had greater impairments in attention, executive function, and visuospatial ability, while mild AD patients performed significantly worse on memory tests. Linear stepwise discriminant analysis indicated that the M emory and E xecutive S creening's 5-min delayed recall test was the best neuropsychological discriminator between mild DLB and mild AD . Conclusions Different patterns of cognitive impairment facilitate the differentiation of mild DLB from mild AD . For patients with mild dementia, better performance on the M emory and E xecutive S creening's 5-min delayed recall test suggests that the diagnosis is more likely DLB than AD .

Rapid cognitive decline (RCD) occurs in dementia due to Alzheimer's disease (AD).Literature review, consensus meetings, and a retrospective chart review of patients with probable AD were conducted.Literature review showed that RCD definitions varied. Mini-Mental State Examination scores20 at treatment onset, vascular risk factors, age70 years at symptom onset, higher education levels, and early appearance of hallucinations, psychosis, or extrapyramidal symptoms are recognized RCD risk factors. Chart review showed that RCD (Mini-Mental State Examination score decline ≥3 points/year) is more common in moderate (43.2%) than in mild patients (20.1%; P .001). Rapid and slow decliners had similar age, gender, and education levels at baseline.RCD is sufficiently common to interfere with randomized clinical trials. We propose a 6-month prerandomization determination of the decline rate or use of an RCD risk score to ensure balanced allocation among treatment groups.

Given that extensive cerebral regions are co-atrophic in semantic dementia (SD), it is not yet known which critical regions (SD-semantic-critical regions) are really responsible for the semantic deficits of SD. To identify the SD-semantic-critical regions, we explored the relationship between the degree of cerebral atrophy in the whole brain and the severity of semantic deficits in 19 individuals with SD. We found that the gray matter volumes of two regions [left fusiform gyrus (lFFG) and left parahippocampal gyrus (lPHG)] significantly correlated with the semantic scores of patients with SD. Importantly, the effects of the lFFG remained significant after controlling for the gray matter volumes of the lPHG. Moreover, the effects of the region could not be accounted for by the total gray matter volume, general cognitive ability, laterality of brain atrophy, or control task performance. We further observed that each atrophic portion of the lFFG along the anterior-posterior axis might dedicate to the loss of semantic functions in SD. These results reveal that the lFFG could be a critical region contributing to the semantic deficits of SD.

OBJECTIVE Chronic frontal hemodynamic disturbances are associated with executive dysfunction in adult patients with moyamoya disease (MMD). However, the impact of surgical revascularization on executive dysfunction and its underlying mechanism remains unclear. The aim of the present study was to examine the postoperative radiological correlates of cognitive improvement and thereby explore its underlying mechanism. METHODS Fourteen patients who met the inclusion criteria were identified at Huashan Hospital, were operated on, and were successfully followed up for 6 months. Postoperative changes in cortical perfusion and regional amplitude of low-frequency fluctuations (ALFF) were examined by SPECT and resting-state functional MRI, respectively. Executive function was evaluated by 2 tests (Trail Making Test Part B and the summation of executive subtests of Memory and Executive Screening [MES-EX]). Follow-up neuropsychological outcomes were then correlated with radiological changes to identify nodes functioning as leading contributors to postoperative executive outcomes. RESULTS All patients underwent successful unilateral bypass procedures, with some operations performed on the left side and some on the right side. At the 6-month follow-up, the baseline and follow-up test scores for the different sides did not differ significantly. The group with good collaterals (Matsushima Grade A, 9 patients) exhibited significantly increased postoperative perfusion (change in [△] hemodynamics) in bilateral frontal (left, p = 0.009; right, p = 0.003) and left parietal lobe (p = 0.014). The Spearman's correlation test suggested that only the right frontal lobe exhibited significant positive postoperative radiological correlates with cognitive performance (△MES-EX vs △hemodynamics, r = 0.620, p = 0.018; △MES-EX vs △ALFF, r = 0.676, p = 0.008; △hemodynamics vs △ALFF, r = 0.547, p = 0.043). Subsequent regional ALFF analysis revealed that the right dorsolateral prefrontal cortex (DLPFC) was the only node in the responsible hemisphere to exhibit significant postoperative changes. CONCLUSIONS The results not only advance our understanding of pathological interactions of postoperative executive performance in adult MMD, but also indicate that the right DLPFC amplitude might be a quantitative predictor of postoperative executive control improvement.

Aberrant local connectivity within cerebral intrinsic connectivity networks (ICNs) at rest has not been reported in adult moyamoya disease (MMD). Our aim was to examine the regional homogeneity (ReHo) of executive control (ECN), default mode (DMN), and salience networks (SN) in patients with executive dysfunction to explore the underlying mechanism. Twenty-six adult patients with MMD and 24 normal control (NC) subjects were recruited. Executive function was evaluated by Trail Making Test Part B (TMT-B) and executive subtests of Memory and Executive Screening (MES-EX). Compared with NC, the case group exhibited ReHo decrease mainly in the frontal and parietal gyrus, and increase only in the left middle temporal gyrus. Subsequent ICNs analysis indicated that compared with NC, patients with MMD exhibited significantly decreased ReHo in the dorsolateral prefrontal cortex (DLPFC) and inferior parietal gyrus (IPG) of left ECN; the IPG, superior frontal gyrus, and DLPFC of the right ECN; the right precuneus, left medial superior frontal gyrus, and right medial orbitofrontal gyrus of the DMN; as well as the left middle frontal gyrus and right supplemental motor area of SN. When referring to the Suzuki's 6-stage classification, a trend of ReHo decrease with disease severity was observed in all of the ICNs examined, but only bilateral ECNs reached statistical significance. Finally, only bilateral ECNs exhibited a significant correlation of averaged ReHo values with executive performance. Our results provide new insight into the pathophysiology of adult MMD.

Compelling evidence has shown that exposure to anesthetics used in the clinic can cause neurodegeneration in the mammalian developing brain, but the basis of this is not clear. Neurotoxicity induced by exposure to anesthestics in early life involves neuroapoptosis and impairment of neurodevelopmental processes such as neurogenesis, synaptogenesis and immature glial development. These effects may subsequently contribute to behavior abnormalities in later life. In this paper, we reviewed the possible mechanisms of anesthetic-induced neurotoxicity based on new in vitro and in vivo findings. Also, we discussed ways to protect against anesthetic-induced neurotoxicity and their implications for exploring cellular and molecular mechanisms of neuroprotection. These findings help in improving our understanding of developmental neurotoxicology and in avoiding adverse neurological outcomes in anesthesia practice.

Non-amnestic mild cognitive impairment (naMCI) is one of the clinical subtypes of mild cognitive impairment (MCI). However, the characteristics of memory deficits in naMCI as assessed by clinical neuropsychological evaluations are not clear. In this study, a battery of neuropsychological tests was administered to 122 cognitively normal controls (NC), 133 amnestic mild cognitive impairment (aMCI) patients, and 72 naMCI patients. The results showed that in individuals with naMCI, episodic memory, and other cognitive domains were impaired. The Prospective Memory Test (PMT) event-based prospective memory (EBPM), the Symbol Digit Modalities Test (SDMT) Accidental Memory, Stick test (ST) visuoconstructional memory, and ST Working Memory were impaired, yet did not reach the level of aMCI. Semantic memory was affected to a degree comparable with aMCI. Some functions like Auditory Verbal Learning Test (AVLT) recognition, and Judgment of Confidence (JOC) were maintained, as well as PMT Time-Based Prospective Memory (TBPM). This study verified that memory impairment among individuals with naMCI was mainly in memory functions mediated by the frontotemporal cortex.

We aimed to investigate the natural history of Alzheimer's disease (AD) and the risk factors associated with survival. We performed a 5-year retrospective cohort study on 467 consecutive outpatients clinically diagnosed with AD and treated between January 1, 2003, and December 31, 2006, at Huashan Hospital, Shanghai, China. The primary endpoint in this study was survival. At baseline, we evaluated the patients' demographic characteristics and neuropsychological characteristics, comorbid conditions, neuroimaging findings, complications, and neurological signs. Among the 467 patients, 398 survived. Male gender, age, and disease severity were associated with mortality. Survival analysis using the proportional hazard model with adjustments for gender, age, and disease stage revealed that the cognition factors that predicted longer survival included high total score [hazard ratio (HR), 0.85; 95% confidence interval (CI), 0.76-0.96] and sub-scores in the verbal fluency test (animals, vegetables, and fruits). The presence of at least 1 complication was an independent factor predictive of a decreased lifespan (HR, 5.55; 95% CI, 1.91-16.13). In AD patients, presence of complications was an indicator of poor survival, while good performance in assessments of executive function, such as the verbal fluency test and Stroop test, at baseline was associated with longer survival.

The present retrospective study was to explore the clinical value of Six-Item Screener (SIS), which is constituted by 6 items from mini-mental status examination (MMSE), to identify cognitive impairment.A total number of 1976 patients aged over 50 years, from the Memory Clinic of Huashan Hospital were employed in a battery of neuropsychological tests including MMSE. Subjects with severe conditions, unable to cooperate, or having been previously enrolled, were excluded from this study. The employed subjects were divided into 3 groups: subjective memory complaints (SMCs) (475 cases), patients with mild cognitive impairment (MCI) (440 cases), and patients with Alzheimer's disease (AD) (1061 cases, including 555 mild, 339 moderate, and 167 severe). A total score of MMSE and a score of SIS composed of date, month, year, three-word delayed recall from MMSE were calculated. Data were analyzed based on educational background.The cut-off of SIS score was2 for illiterate,3 for elementary, and4 for junior high school or above. The sensitivity and specificity of SIS for detecting mild AD were 88.5% and 78.3%, respectively, with an overall accuracy of 83.8%, while for detecting MCI, the sensitivity and specificity were 34.3% and 90.1%, respectively, with an overall accuracy of 63.2%.SIS is an effective and reliable instrument for dementia detection in outpatient department. However, it has limited value for MCI identification.

Background Despite rapid development of epidemiology in dementia, reported prevalence in Asia varies among studies and differs from that of Western countries. Few reported the mortality and predictive factors on survival of dementia in Asia, especially China. Methods To characterize the epidemiologic pattern of dementia in Shanghai, China, including prevalence and survival, we conducted a cross-sectional, population-based survey among Shanghai residents (> or =55 y) and followed a subsample for up to 40 months for survival analysis. A stratified, multistage cluster sampling design was adopted. Results Crude and age-standardized prevalence of dementia was 2.99% and 2.66%, respectively, higher in women and increased with age. Prevalence of Alzheimer was higher than vascular dementia. Furthermore, Alzheimer disease was more prevalent in rural areas than in urban, whereas geographic distribution of vascular dementia was quite the opposite. Crude and age-standardized mortality of dementia was 6.06 and 5.30 per 1000 person-years. There was a striking difference in survival between the demented and nondemented, whereas no significant survival discrepancy existed between Alzheimer and vascular dementia. Factors including overall physical and cognitive function, age, and severity of disease strongly influenced survival and might be predictors for fatal events in dementia patients. Conclusions The epidemiologic pattern of dementia in Shanghai, China is similar to that of western countries.

Objective: To determine apolipoprotein E (APOE)-ε4 and -ε2 frequencies and risk of mild cognitive impairment (MCI) and dementia in Shanghai, China. Methods: A total of 34 MCI and 34 dementia cases were recruited from an urban Memory Disorders Clinic and 32 controls were recruited from a residential community served by the clinic. Apolipoprotein E was genotyped using standard methods. Results: Among controls, frequencies were ε2, 0.11; ε3, 0.84; and ε4, 0.05; among MCI, 0.05, 0.77, and 0.18; and for dementia, 0.02, 0.84, and 0.15, respectively. In education-adjusted models, the odds ratio (OR) = 5.6 for dementia (95% CI = 1.09-29.3) and 4.7 for MCI (95% CI = 0.90-25.2) associated with any ε4 allele. The ε2 allele was inversely associated with dementia (OR = 0.12, 95% CI = 0.013-0.997) and MCI (OR = 0.38, 95% CI = 0.08-1.61). Conclusions: APOE-ε4 increases and -ε2 decreases the risk of dementia vs normal cognition. Similar trends were observed for amnestic mild cognitive impairment (aMCI).

Objective: To examine whether 3 common memory tests differ statistically in terms of mild cognitive impairment (MCI) discrimination rates and conversion rates to Alzheimer disease. Methods: A sample of 329 Chinese patients who consulted our memory clinic in Shanghai were tested using tasks including the auditory verbal learning test (AVLT), the logical memory (LM) test, the Rey-Osterrieth complex figure test, and other neuropsychologic tasks. One hundred and forty-nine of these patients were tested again using the identical tests 2 years later. The diagnose standard of probable Alzheimer disease is the same as the standard of the National Institute of Neurological and Communicative Diseases and Stroke-Alzheimer Disease and Related Disorders Association. Results: The results of the MCI discrimination rates are as follows: AVLT-II(51%) > AVLT-I (31%) > complex figure test-II (27%) > LM-1 (21%) = LM-II (21%) (1―immediate recall; II―delayed recall). The MCI group categorized based on LM-II cutoff has a higher conversion rate per year (24%), but also a higher reversal rate and missed diagnosis rate, whereas the group based on AVLT-II cutoff has a lower conversion rate per year (12%), but also a lower reversal rate and missed diagnosis rate. Conclusions: The MCI discrimination rate and the conversion rate among different episodic memory tests are differ considerably.

Objective: Establish cohort of patients with mild cognitive impairment (MCI) in order to identify the risk factors and validation of neuropsychological tests for early detection of Alzheimer disease. Methods: Four hundred participants with MCI were enrolled in at Huashan Hospital in Shanghai, China. All patients will be followed once annually for 3years. The primary endpoint is the time of conversion from diagnosis of MCI to Alzheimer disease (AD). Results: of the 400 subjects, 170 (42.5%) were male, and the average mean age and education was 68.7 (Standard Deviation, SD: 8.2, 45- 90 years old) and 12 years (SD: 3.1), respectively. At baseline age, education and being single influenced MMSE, ADAS-cog13 and most domains of cognition. Conclusions: Baseline characteristics of the Shanghai MCI cohort study indicate the participants were younger, less educated and had a moderate gender ratio compared to other studies conducted so far and represent the target population. 3 years later when the cohort will be finished some risk factors Associated with the conversion will be validated and some novel factors will be identified.

The representation of object categories is a classical question in cognitive neuroscience and compelling evidence has identified specific brain regions showing preferential activation to categories of evolutionary significance. However, the potential contributions to category processing by tuning the connectivity patterns are largely unknown. Adopting a continuous multicategory paradigm, we obtained whole‐brain functional connectivity (FC) patterns of each of four categories (faces, scenes, animals and tools) in healthy human adults and applied multivariate connectivity pattern classification analyses. We found that the whole‐brain FC patterns made high‐accuracy predictions of which category was being viewed. The decoding was successful even after the contributions of regions showing classical category‐selective activations were excluded. We further identified the discriminative network for each category, which span way beyond the classical category‐selective regions. Together, these results reveal novel mechanisms about how categorical information is represented in large‐scale FC patterns, with general implications for the interactive nature of distributed brain areas underlying high‐level cognition. Hum Brain Mapp 37:3685–3697, 2016. © 2016 Wiley Periodicals, Inc.

Chinese processing has been suggested involving distinct brain areas from English. However, current functional localization studies on Chinese speech processing use mostly “indirect” techniques such as functional magnetic resonance imaging and electroencephalography, lacking direct evidence by means of electrocortical recording. In this study, awake craniotomies in 66 Chinese‐speaking glioma patients provide a unique opportunity to directly map eloquent language areas. Intraoperative electrocortical stimulation was conducted and the positive sites for speech arrest, anomia, and alexia were identified separately. With help of stereotaxic neuronavigation system and computational modeling, all positive sites elicited by stimulation were integrated and a series of two‐ and three‐dimension Chinese language probability maps were built. We performed statistical comparisons between the Chinese maps and previously derived English maps. While most Chinese speech arrest areas located at typical language production sites (i.e., 50% positive sites in ventral precentral gyrus, 28% in pars opercularis and pars triangularis), which also serve English production, an additional brain area, the left middle frontal gyrus (Brodmann's areas 6/9), was found to be unique in Chinese production (P

Background The aim of this study was to explore the neuroanatomical bases of vascular mild cognitive impairment (VaMCI) with respect to attention/executive function, memory, language, and visuospatial function. Methods We used voxel-based morphometric analysis to identify brain regions that significantly differed in terms of gray matter volumes (GMVs) between 43 patients with VaMCI and 55 healthy controls. Then, we compared the individual GMVs of the selected regions with the neuropsychological profiles of the VaMCI patients. Results The delayed recall component of the Rey–Osterrieth Complex Figure Test (CFT) (74.4%), the Symbol Digit Modalities Test (74.4%), the Boston Naming Test (51.2%), and the CFT—copy (81.4%) shared the highest incidence of impairment in the 4 cognitive domains, respectively. Compared with controls, patients with VaMCI exhibited significantly reduced GMVs. This effect was mainly present in the frontal regions, including the bilateral dorsolateral prefrontal cortex (DLPFC), the orbital portion of the superior frontal gyrus (SFG), and the left supplemental motor area, and was also observed in the bilateral posterior cingulated cortex (PCC). GMVs were significantly correlated with performance in the Trail Making Test, part B, in the bilateral DLPFC and PCC, the clock drawing test in the right orbital portion of the SFG, and CFT—delayed recall in the right PCC. Conclusions These results, from the perspective of brain morphology, uniquely explored the specific cerebral structural changes of VaMCI, thus providing a deeper understanding of the pathophysiology of the disease.

Background: Anthropometric indexes are powerful indicators of the environment and the plasticity of the human body. This study aimed at exploring the anthropometric indexes that are associated with late-life cognition impairment among the elderly Chinese in the Shanghai Aging Study. Methods: The height, weight, and sitting height of 3,741 participants were measured. Participants were diagnosed with ‘dementia', ‘mild cognitive impairment', or ‘cognitive normal' by neurologists using DSM-IV and Petersen criteria. Logistic regression was used to evaluate the association between height, sitting height, leg length or relative sitting height and cognitive function. Results: Participants with dementia had the shortest body height (mean 157.2 cm, SD 9.1), the shortest sitting height (mean 81.8 cm, SD 5.6), and the lowest relative sitting height (mean 52.0 cm, SD 1.9). After adjustment for age, gender, education, lifestyles, medical history, apolipoprotein genotype and weight, shorter sitting height (OR 1.08, 95% CI 1.01-1.16 per cm), longer leg length (OR 0.93, 95% CI 0.88-0.99 per cm), and lower relative sitting height (OR 1.17, 95% CI 1.04-1.31 per 1%) were found to be significantly associated with dementia in older women. Conclusions: The potential risks for late-life severe cognitive impairment may be related to health problems in childhood and slow growth during puberty in women.

Objective : To carry out meaningful comparisons on results of different research studies on mild cognitive impairment (MCI), it is critical to select an appropriate objective memory test to examine memory deficit. We aim to refine the operational criteria of amnestic MCI (aMCI) on neuropsychological tests that optimally balance the sensitivity and specificity. Methods : We focused on 206 non-demented subjects from memory clinic. We then classified each individual as having MCI or subjective cognitive decline (SCD) according to different neuropsychological criteria. By following them longitudinally, clinical outcomes were compared to evaluate the stability of MCI diagnoses and prediction of progression. Results : The delayed recall of auditory verbal learning test (AVLT_DR) identified 116 subjects as MCI, resulted in the conversion rate as 44% over the roughly 30-month time interval, missed 7.8% incipient Alzheimer’s disease (AD) patients in SCD group who eventually converted to dementia. The delayed recall of complex figure test (CFT_DR) identified fewer MCI patients (n=95) and misdiagnosed more preclinical AD patients (15.3%), in comparison with AVLT criterion. Criterion requiring deficits in both tests produced higher conversion rate (54.3%), but resulted in higher misdiagnosis rate (14.7%) simultaneously. The AVLT criterion had the largest area under the curve (0.7248, p Conclusion : AVLT is superior to CFT in the stability of diagnoses and prediction of progression. In the clinical setting, the “one test” criterion AVLT has similar sensitivity to both-deficits methods, and is optimal in balancing sensitivity and specificity.

Summary Semantic dementia (SD) is a neurodegenerative disorder characterized by the progressive loss of semantic memory and conceptual knowledge, coupled with asymmetric local brain atrophy concentrated in the anterior temporal lobe. Recent developments in neuroimaging techniques, especially the emergence of the “human connectomics,” have made possible the study of the brain's functional and structural connections and the topological properties of the brain networks. Recent studies applying these techniques have shown that SD manifests extensive structural and functional connectivity alterations, providing important insights into the pathogenesis of SD and the neural basis of semantic memory in general. In this review, we present and discuss the existing findings about the brain connectivity changes in SD and how they might be related to the various behavioral deficits associated with this disorder and propose important unanswered questions that warrant further investigation.

Background Oral health has been found to be associated with cognitive function in basic research and epidemiology studies. Most of these studies had no comprehensive clinical diagnosis on cognitive function. This study firstly reported the association between tooth loss and cognitive function among Chinese older population. Methods The study included 3,063 community dwelling older adults aged 60 or above from the Shanghai Aging Study. Number of teeth missing was obtained from self-reporting questionnaire and confirmed by trained interviewers. Participants were diagnosed as “dementia”, “mild cognitive impairment (MCI)”, or “cognitive normal” by neurologists using DSM-IV and Petersen criteria. Multivariate logistic regression model was applied to examine the association between number of teeth missing and cognitive function. Results The study participants had an average of 10.2 teeth lost. Individuals with dementia lost 18.7 teeth on average, much higher than those with MCI (11.8) and cognitive normal (9.3) (p16 were significantly associated with dementia with an OR of 1.56 (95%CI 1.12-2.18). Conclusion Having over 16 missing teeth was associated with severe cognitive impairment among Chinese older adults. Poor oral health might be considered as a related factor of neurodegenerative symptom among older Chinese population.

The apolipoprotein E (APOE) ϵ4 allele is a confirmed genetic risk factor and the APOE ϵ2 allele is a protective factor related to late-onset Alzheimer's disease (AD). Intriguingly, recent studies demonstrated similar brain function alterations between APOE ϵ2 and ϵ4 alleles, despite their opposite susceptibilities to AD. To address this apparent discrepancy, we recruited 129 cognitively normal elderly subjects, including 36 ϵ2 carriers, 44 ϵ3 homozygotes, and 49 ϵ4 carriers. All subjects underwent resting-state functional MRI scans. We hypothesized that aging could influence the APOE ϵ2 and ϵ4 allele effects that contribute to their appropriate AD risks differently. Using the stepwise regression analysis, we demonstrated that although both ϵ2 and ϵ4 carriers showed decreased functional connectivity (FC) compared with ϵ3 homozygotes, they have opposite aging trajectories in the default mode network-primarily in the bilateral anterior cingulate cortex. As age increased, ϵ2 carriers showed elevated FC, whereas ϵ4 carriers exhibited decreased FC. Behaviorally, the altered DMN FC positively correlated with information processing speed in both ϵ2 and ϵ4 carriers. It is suggested that the opposite aging trajectories between APOE ϵ2 and ϵ4 alleles in the DMN may reflect the antagonistic pleiotropic properties and associate with their different AD risks.

To compare vascular cognitive impairment-no dementia (VCI-ND) using different classification methods.We recruited 56 patients with VCI-ND between April 2012 and March 2013. We used a battery of neuropsychological tests to classify patients with VCI-ND into different subtypes based on memory and executive function as follows: cognitive screening (Mini-Mental State Examination, MMSE), memory (Auditory Verbal Learning Test, AVLT), executive/attention (Shape Trails Test, STT; Stroop Color-Word Test, SCWT; Reading the Mind in the Eyes, RME; Digit Ordering Test-A, DOT-A; Symbol Digit Modalities Test, SDMT), language (Action Naming Test, ANT; Boston Naming Test, BNT; Famous Face Test, FFT; Similarity Test, ST; Verbal Fluency Test, VFT) and visuospatial function (Complex Figure Test, CFT).The two groups had comparable demographic information (P0.05). Amnestic VCI-ND (aVCI-ND) patients obtained significantly lower scores compared with individuals with nonamnestic VCI-ND (naVCI-ND) on the AVLT memory test, VFT language test and VFT-alternating executive test (P0.05). Additionally, executive VCI-ND (eVCI-ND) patients performed significantly longer than nonexecutive VCI-ND (neVCI-ND) patients on the SCWT-C timed executive test. Finally, eVCI-ND patients obtained significantly lower scores compared with neVCI-ND patients on the RME, DOT-A and SDMT-correct executive tests and the ANT, BNT and ST language tests (P0.05).aVCI-ND patients performed poorly compared with naVCI-ND patients in terms of executive and language functions, while eVCI-ND patients performed poorly compared with neVCI-ND patients in terms of language function.

To explore the characteristics of cognitive impairment of cerebral ischemia in adults to provide rationales for proper diagnosis and targeted treatment.A battery of standardized neuropsychological tests including mini-mental state examination (MMSE) and memory and executive screening (MES) was administered in a cohort of consecutive patients with cerebral ischemia. According to the screening results, they were divided into 3 subgroups of vascular dementia (VaD), vascular mild cognitive impairment (VaMCI) and non-vascular cognitive impairment (VCI). The general profiles of 3 subgroups were compared and the characteristics of VaMCI subgroup examined. Then the relationship between the composition of cognitive impairment and the type of ischemia (stroke and transient ischemic attack) was analyzed.Fifty-six patients and 48 healthy subjects (normal control group) matched with regards to age, gender and education were recruited. Compared to normal control group, there was a decline in the scores of MMSE [(25.0 ± 5.6) vs (28.0 ± 1.4); t = 2.695, P = 0.007] and MES [(67 ± 21) vs (84 ± 7); z = 3.860, P = 0.000] in case group. There were 33 cases (58.9%) of VCI in case group, including 11 (19.6%) in VaD subgroup, 22 (39.3%) in VaMCI subgroup and 23 (41.1%) in non-VCI subgroup. And the rate of VaD/VaMCI was 1/2. The percentage of males (36.4% vs 78.3%; χ(2) = 5.720, P = 0.017) and education [(8 ± 3) vs (12 ± 4); P = 0.010] of VaD subgroup were significantly lower than that of non-VCI subgroup; the education of VaMCI subgroup was significantly lower than that of non-VCI subgroup [(7 ± 3) vs (12 ± 4); P = 0.001]; a positive correlation existed between scores of MMSE/MES and cognitive impairment. The neuropsychological tests were both sensitive and specific.In VaMCI subgroup, 22 cases (100%) presented with a deficit of at least 1 certain executive function/attention index, 21(95.5%) with at least 1 certain memory index, 17(77.3%) with at least 1 certain language index and 16(72.7%) with at least 1 certain visuospatial function index; all VaMCI cases presented with comprehensive cognitive impairment: 11 (50%) in 4 domains, 10 (45%) in 3 domains and 1 (5%) in 2 domains.No significant difference existed among 3 subgroups with regard to type of ischemia (χ(2) = 1.111, P = 0.574). In the case group, 30 patients suffered stroke and 17 (56.7%) had an onset of VCI with a rate of VaMCI/VCI at 58.8%; transient ischemic attack occurred in 26 patients and 16 (61.5%) suffered VCI with a rate of VaMCI/VCI at 75.0%.Our study not only profiles the prevalence and peculiarity of cognitive impairment in patients with cerebral ischemia, but also provides concrete rationales for further diagnosis and classification of VCI.

Objectives Progressive cognitive decline is a characteristic hallmark of AD. It is important to identify prognostic markers to improve patient care and long-term planning. We aimed to identify the characteristics of disease progression in AD patients, focusing on cognitive decline and its related factors. Methods Clinically diagnosed AD patients in a memory clinic were followed. The mini–mental state examination (MMSE) and a battery of other neuropsychological tests were performed to assess the rate of cognitive decline and to analyze the related factors. Results A total of 165 AD patients were analyzed for cognitive changes. The MMSE scores declined at a rate of 1.52 points per year. Most neuropsychological test scores deteriorated significantly over time. Younger and early-onset AD patients deteriorated more rapidly than older and late-onset patients in global cognition and executive function. Men declined faster in memory but slower in attention than women. Higher education was associated with more rapid deterioration in visuo-spatial ability. Family history, hypertension and cerebral vascular disease were also associated with disease progression. Conclusion Attention, executive and visuo-spatial functions deteriorate at faster rates than other cognitive functions in AD patients. Age and age at onset were the main factors that associated with deterioration.

Background Many scoring systems exist for clock drawing task variants. However, none of them are reliable in evaluating longitudinal changes of cognitive function. The purpose of this study is to create a simple yet optimal scoring procedure to evaluate cognitive decline using a clinic-based sample. Methods Clock-drawings from 121 participants (76 individuals with no dementia and later did not develop dementia after a mean 41.2-month follow-up, 45 individuals with no dementia became demented after a mean 42.3-month follow-up) were analyzed using t-test to determine a new and simplified CDT scoring system. The new scoring method was then compared with other commonly used systems. Results In the converters, there were only 7 items that are significantly different between the initial visits and the second visits. We propose a new scoring system that includes the seven critical items: numbers are equally spaced (12–3–6–9) (p = 0.031), the other eight numbers are marked (p = 0.022), numbers are clockwise (p = 0.002), all numbers are correct (p = 0.030), distance between numbers is constant (p = 0.016), clock has two hands (p = 0.000), arrows are drawn (p = 0.003). Compared with other traditionally used scoring methods, this based change clock drawing test (BCCDT) has one of the most balanced sensitivities/specificities with a clinic-based sample. Conclusions The new CDT scoring system provides further evidence in support of a simple and reliable clock-drawing scoring system in follow-up studies to evaluate cognitive decline, which can be used in assessing the efficacy of medicine.

Background: There is a paucity of research assessing health-related quality of life (HRQoL) and self-efficacy in caregivers of relatives with dementia in mainland China. Aims: To compare the level of HRQoL between caregivers and the general population in mainland China and to assess the role of caregiver self-efficacy in the relationship between caregiver social support and HRQoL. Methods: A cross-sectional study was conducted in Shanghai, China. The caregivers were recruited from the outpatient department of a teaching hospital. A total of 195 participants were interviewed, using a survey package including the Chinese version of the 36-Item Short-Form Health Survey (SF-36), demographic data, the variables associated with the impairments of care recipients, perceived social support and caregiver self-efficacy. The caregivers' SF-36 scores were compared with those of the general population in China. Results: The results indicated that the HRQoL of the caregivers was poorer compared with that of the general population when matched for age and gender. Multiple regression analyses revealed that caregiver self-efficacy is a partial mediator between social support and HRQoL, and a partial mediator between behavioral and psychological symptoms of dementia (BPSD) and caregiver mental health. Conclusion: Assisting with managing BPSD and enhancing caregiver self-efficacy can be considered integral parts of interventions to improve caregiver HRQoL.

BACKGROUND: Sleep disorders causes a significant negative effect on mental and physical health, particularly among the elderly. The disease burden and risk factors of poor sleep quality of the elderly need to be verified using a validated form of measurement in urban mainland China. METHODS: This study included 1086 community residents aged ≥ 60 years who completed the Chinese version of the Pittsburgh Sleep Quality Index (CPSQI). Poor sleeper was defined by a CPSQI global score of >5. Subjects also accepted the neurological and neuropsychological assessments, including the Mini-Mental State Examination, Center for Epidemiological Studies Depression Scale, and Zung Self-Rating Anxiety Scale (ZSAS). A history of chronic diseases was confirmed by the medical records of each participant. RESULTS: The prevalence of poor sleep quality in this population was 41.5% (95% confidence interval (CI) = 38.6-44.5%), with a higher rate observed in elderly females (45.8% [95% CI = 41.9-49.7%]) than that in elderly males (35.8% [95% CI = 31.4-40.1%]). The prevalence rate increased with age, from 32.1% (95% CI = 27.8-36.4%) in those aged 60-69 years to 52.5% (95% CI = 45.9-59.1%) in those aged ≥ 80 years (p value for trend

Summary Aims Alzheimer's disease (AD) and Parkinson's disease (PD) are the most prevalent neurodegenerative disorders that may share some overlapping etiologies. Mutations within leucine-rich repeat kinase 2 (LRRK2) have been reported to be responsible for PD, and the location of LRRK2 is within a linkage peak for sporadic AD (SAD). The aim of this study was to investigate two Asian-specific LRRK2 variants, R1628P and G2385R, with the association of Han Chinese SAD. Methods Genotyping of R1628P and G2385R was performed by PCR-restriction fragment length polymorphism (RFLP) analysis in 390 patients with SAD and 545 unrelated age- and sex-matched healthy controls. Results The frequency of the C allele within R1628P was more than three times higher in control group (1.7%) than in patients with SAD (0.5%) (OR 0.264; 95% CI, 0.088–0.792, P = 0.018). After stratification by the presence of one or two apolipoprotein E e4 alleles, the protective effect becomes stronger (e44: OR 0.028; 95% CI, 0.003–0.303, P = 0.003; e4: OR 0.104; 95% CI, 0.013–0.818, P = 0.031). However, no difference was found in G2385R variant. Conclusion Our study suggested that R1628P variant within LRRK2 plays a protective role in Han Chinese population with SAD and such effect has an interaction with the APOE genotype.

Background and Purpose— We explored the association between pulsatility index (PI) as derived from transcranial Doppler ultrasound with various measures of small vessel disease in the community. Methods— We performed transcranial Doppler and magnetic resonance imaging in 205 consecutive community-dwelling elderly subjects who were participants of the Shanghai Aging Study. We investigated the association between middle cerebral artery (MCA) PI with measures of white matter lesions (WML), lacunes, and microbleeds. Results— Multiple logistic regression found that MCA PI was associated with severe WML (odds ratio, 1.33 per 0.1 increase in PI; 95% confidence interval, 1.04–1.70; P =0.02). At optimal MCA PI cut-off, the area under curve, positive predictive value, and negative predictive value were 0.70 (95% confidence interval, 0.60–0.80), 34.9%, and 85.6%, respectively, for detection of severe WML. No association was found between MCA PI and measures of lacunes or microbleeds. Conclusions— PI correlates with WML severity. With a high negative predictive value, the chance of having severe WML with a normal PI is low. Transcranial Doppler may guide selective magnetic resonance imaging scanning for the detection of WML in the community.

Delayed recall of words in a verbal learning test is a sensitive measure for the diagnosis of amnestic mild cognitive impairment (aMCI) and early Alzheimer's disease (AD). The relative validity of different retention intervals of delayed recall has not been well characterized. Using the Auditory Verbal Learning Test-Huashan version, we compared the differentiating value of short-term delayed recall (AVL-SR, that is, a 3- to 5-minute delay time) and long-term delayed recall (AVL-LR, that is, a 20-minute delay time) in distinguishing patients with aMCI (n = 897) and mild AD (n = 530) from the healthy elderly (n = 1215). In patients with aMCI, the correlation between AVL-SR and AVL-LR was very high (r = 0.94), and the difference between the two indicators was less than 0.5 points. There was no difference between AVL-SR and AVL-LR in the frequency of zero scores. In the receiver operating characteristic curves analysis, although the area under the curve (AUC) of AVL-SR and AVL-LR for diagnosing aMCI was significantly different, the cut-off scores of the two indicators were identical. In the subgroup of ages 80 to 89, the AUC of the two indicators showed no significant difference. Therefore, we concluded that AVL-SR could substitute for AVL-LR in identifying aMCI, especially for the oldest patients.

Diabetes is thought to contribute to cognitive impairment in the elderly. The risk may be modified by genetic factors such as apolipoprotein E (APOE). We aim to determine the prevalence of dementia in Chinese diabetics and non-diabetic individuals, and assess the effect of the APOE genotype. A cross-sectional study was conducted among participants aged 50 and over in an urban community. Subjects were 1:1 matched for age and gender (diabetes group (n = 497) versus non-diabetes group (n = 497)). Each subject was interviewed for dementia and related risk factors. Fasting blood samples were drawn for glucose and APOE. Subjects were screened using the Mini Mental State Examination (MMSE) and were examined by a series of neuropsychological tests if screened positive (indicated by an MMSE score below 19, 21, and 24, respectively according to different educational attainment). A diagnosis of dementia was defined according to DSM-IV criteria. The prevalence of all-cause dementia, Alzheimer's disease, and vascular dementia in diabetics (4.8%, 2.7%, 1.4%) was higher than that of non-diabetics (2.2%, 1.2%, 0.4%) (all-cause dementia, diabetics versus non-diabetics, p < 0.05). APOE e4 carriers had higher prevalence of dementia and AD (diabetics: 9.2%, 7.55%, non-diabetics: 3.3%, 3.3%) than APOE e4 non-carriers (diabetics: 6.3%, 2.3%, non-diabetics: 2.35%, 0.7%) (p < 0.05). Diabetics carrying the APOE e4 allele had a 3.982-fold [95%CI, 1.418-11.184] likelihood of having dementia compared with those without these two factors. This study showed that the prevalence of dementia was significantly higher in diabetics than non-diabetics. APOE e4 further enhanced the risk.

Physical exercise has been shown to increase brain volume and improve cognition in randomized trials of non-demented elderly. Although greater social engagement was found to reduce dementia risk in observational studies, randomized trials of social interventions have not been reported. A representative sample of 120 elderly from Shanghai, China was randomized to four groups (Tai Chi, Walking, Social Interaction, No Intervention) for 40 weeks. Two MRIs were obtained, one before the intervention period, the other after. A neuropsychological battery was administered at baseline, 20 weeks, and 40 weeks. Comparison of changes in brain volumes in intervention groups with the No Intervention group were assessed by t-tests. Time-intervention group interactions for neuropsychological measures were evaluated with repeated-measures mixed models. Compared to the No Intervention group, significant increases in brain volume were seen in the Tai Chi and Social Intervention groups (p < 0.05). Improvements also were observed in several neuropsychological measures in the Tai Chi group, including the Mattis Dementia Rating Scale score (p = 0.004), the Trailmaking Test A (p = 0.002) and B (p = 0.0002), the Auditory Verbal Learning Test (p = 0.009), and verbal fluency for animals (p = 0.01). The Social Interaction group showed improvement on some, but fewer neuropsychological indices. No differences were observed between the Walking and No Intervention groups. The findings differ from previous clinical trials in showing increases in brain volume and improvements in cognition with a largely non-aerobic exercise (Tai Chi). In addition, intellectual stimulation through social interaction was associated with increases in brain volume as well as with some cognitive improvements.

Non-amnestic mild cognitive impairment (naMCI) is one of the clinical subtypes of mild cognitive impairment (MCI). However, the characteristics of memory deficits in naMCI as assessed by clinical neuropsychological evaluations are not clear. In this study, a battery of neuropsychological tests was administered to 122 cognitively normal controls (NC), 133 amnestic mild cognitive impairment (aMCI) patients, and 72 naMCI patients. The results showed that in individuals with naMCI, episodic memory, and other cognitive domains were impaired. The Prospective Memory Test (PMT) event-based prospective memory (EBPM), the Symbol Digit Modalities Test (SDMT) Accidental Memory, Stick test (ST) visuoconstructional memory, and ST Working Memory were impaired, yet did not reach the level of aMCI. Semantic memory was affected to a degree comparable with aMCI. Some functions like Auditory Verbal Learning Test (AVLT) recognition, and Judgment of Confidence (JOC) were maintained, as well as PMT Time-Based Prospective Memory (TBPM). This study verified that memory impairment among individuals with naMCI was mainly in memory functions mediated by the frontotemporal cortex.

The small-world organization has been hypothesized to reflect a balance between local processing and global integration in the human brain. Previous multimodal imaging studies have consistently demonstrated that the topological architecture of the brain network is disrupted in Alzheimer's disease (AD). However, these studies have reported inconsistent results regarding the topological properties of brain alterations in AD. One potential explanation for these inconsistent results lies with the diverse homogeneity and distinct progressive stages of the AD involved in these studies, which are thought to be critical factors that might affect the results. We investigated the topological properties of brain functional networks derived from resting functional magnetic resonance imaging (fMRI) of carefully selected moderate AD patients and normal controls (NCs). Our results showed that the topological properties were found to be disrupted in AD patients, which showing increased local efficiency but decreased global efficiency. We found that the altered brain regions are mainly located in the default mode network, the temporal lobe and certain subcortical regions that are closely associated with the neuropathological changes in AD. Of note, our exploratory study revealed that the ApoE genotype modulates brain network properties, especially in AD patients.

Spontaneous low-frequency fluctuations (LFF) in the blood-oxygenation-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) signal have been shown to reflect cerebral spontaneous neural activity. The objective of this study was to explore brain functional changes in patients with mild cognitive impairment (MCI) by measuring the amplitude of the BOLD signals. Eighteen amnestic MCI patients and 20 healthy elderly individuals underwent the fMRI scan. The amplitude of LFF (ALFF) was calculated using REST software. MCI patients showed decreased ALFF in the right hippocampus and parahippocampal cortex, left lateral temporal cortex and right ventral medial prefrontal cortex and increased ALFF in the left temporal-parietal joint (TPJ) and inferior parietal lobule. The ALFF value in the right hippocampus and parahippocampal cortex was positively correlated with the scores of Mini-Mental State Exam. Reduced medial temporal lobe activity may implicate the underlying memory impairment mechanisms in MCI. Increased TPJ and inferior parietal lobule activity may indicate the compensatory mechanism in MCI patients. These findings suggest that ALFF analysis could provide a useful tool in the fMRI study of MCI.

Alzheimer's disease (AD) is the most common form of senile dementia, and the overall prevalence increases exponentially with age. It is well known that genetic variants may play an important role in the pathogenesis of this disorder. Recently, two independent large-scale genome-wide association studies (GWAS) identified 3 novel single nucleotide polymorphisms (SNPs) (rs11136000 within CLU, rs3851179 within PICALM and rs6656401 within CR1) that are associated with late-onset AD (LOAD), and these results have been replicated by other studies performed in the Caucasian population. Recently, an independent study failed to verify the association for the SNP within CLU in a Han Chinese population, indicating that there may be genetic heterogeneity in this association. In the present study, we studied the SNPs within PICALM and CR1 in 474 sporadic AD patients (SAD) and 591 unrelated age- and sex-matched healthy controls of Han Chinese descent. Our data revealed that the frequencies of both of these SNPs were not significantly difference between the SAD and control groups. Thus, the association between SNPs within PICALM, CR1, and SAD should be studied further in different ethnic groups.

Background/Aims: We investigated the clinical and cognitive features of patients with mild general paresis of the insane (GPI) in comparison to Alzheimer’s disease (AD) patients, mild frontotemporal dementia (FTD) patients and normal elderly individuals. Methods: Twelve patients with mild GPI, 24 patients with mild AD, 11 patients with mild FTD and 36 healthy subjects participated in the current study. A comprehensive neuropsychological battery was used to assess memory, language, attention, executive function, visuospatial ability, etc. In addition, cranial MRI were also obtained from the 3 patient groups. Results: Mild GPI showed a similar pattern of cognitive impairments in memory, language and executive function to mild AD, but a mixed pattern of dissimilarities to mild FTD. Mild GPI patients had more complaints and positive signs in the nervous system than mild AD patients, and cranial MRI results showed that mild GPI patients usually had atrophy of the medial temporal lobe. Conclusion: There is an overall decline in cognitive functions of mild GPI patients, which is comparable to that in AD patients, suggesting that there is a wide range of structural changes in the brains of mild GPI patients as well. However, further studies are needed to verify whether these structural changes are similar to those in AD.

Background Diabetes is a risk factor for mild cognitive impairment (MCI) and dementia. However, the association between high normal fasting blood glucose (FBG) and dementia has not been studied. Methods Polytomous logistic regression was used to assess the association of dementia and MCI with FBG in an age- and sex-matched sample of 32 dementia patients, 27 amnestic MCI (aMCI) patients, and 31 normal controls (NC). Analyses were repeated for those with normal FBG. Correlations between FBG and cognitive test scores were obtained. Results Controlling for age, gender, education, body mass index, Hachinski Ischemic Score, magnetic resonance imaging (MRI) stroke, and normalized brain, hippocampal, and white matter hyperintensity MRI volumes; higher FBG was associated with dementia versus aMCI status (OR = 3.13; 95% CI, 1.28–7.69). This association remained (OR = 7.75; 95% CI, 1.10–55.56) when analyses were restricted to subjects with normal FBG. When dementia patients were compared with NC adjusting for age, gender, and education, a significant association with FBG also was seen (OR = 1.83; 95% CI, 1.09–3.08), but it was lost when vascular covariates were added to the model. FBG was not associated with aMCI status versus NC. Higher FBG was correlated with poorer performance on the Trailmaking Test Part B ( P = .003). The percentage of dementia patients with high normal FBG (90%) was significantly higher than that of aMCI patients with high normal FBG (32.9%) (χ 2 = 13.9, P Conclusions Higher FBG was associated with dementia (vs. aMCI) independent of vascular risk factors and MRI indicators of vascular disease, and remained a significant risk factor when analyses were restricted to subjects with normal FBG. The results of this cross-sectional study suggest that a high normal level of FBG may be a risk factor for dementia.

To investigate the associations among brain morphologic changes as seen on magnetic resonance imaging (MRI), cerebrovascular risk (CVR), and clinical diagnosis and cognition in elderly patients with mild cognitive impairment and dementia living in urban Shanghai.Cross-sectional study performed from May 1, 2007, to November 31, 2008.Memory Disorders Clinic of the Huashan Hospital and the Shanghai community.Ninety-six older people: 32 with normal cognition (NC), 30 with amnestic mild cognitive impairment (aMCI), and 34 with dementia.For each patient, we administered a neurologic and physical examination, neuropsychological evaluation, and brain MRI and genotyped the apolipoprotein E-ε4 (APOE-ε4) gene. The volumes determined by MRI were assessed using a semiautomatic method.Brain volume was significantly smaller in the dementia patients compared with the NC (P .001) and aMCI patients (P = .04). Hippocampal volume (HV) was lower and white matter hyperintensity (WMH) volume was higher in those with aMCI (HV: P = .03; WMH volume: P = .04) and dementia (HV: P .001; WMH volume: P = .002) compared with NC participants. The presence of APOE-ε4 was significantly associated with reduced HV (P = .02). Systolic blood pressure was positively associated with CVR score (P = .04); diastolic blood pressure (P = .02) and CVR score (P = .04) were positively associated with WMH volume. The WMH volume (P = .03) and CVR score (P = .03) were higher among dementia patients compared with NC participants.Brain structure changes seen on MRI were significantly associated with clinical diagnosis. In addition, blood pressure was highly associated with CVR score and WMH volume. These results suggest that MRI is a valuable measure of brain injury in a Chinese cohort and can serve to assess the effects of various degenerative and cerebrovascular diseases.

We aimed to investigate the natural history of Alzheimer's disease (AD) and the risk factors associated with survival. We performed a 5-year retrospective cohort study on 467 consecutive outpatients clinically diagnosed with AD and treated between January 1, 2003, and December 31, 2006, at Huashan Hospital, Shanghai, China. The primary endpoint in this study was survival. At baseline, we evaluated the patients' demographic characteristics and neuropsychological characteristics, comorbid conditions, neuroimaging findings, complications, and neurological signs. Among the 467 patients, 398 survived. Male gender, age, and disease severity were associated with mortality. Survival analysis using the proportional hazard model with adjustments for gender, age, and disease stage revealed that the cognition factors that predicted longer survival included high total score [hazard ratio (HR), 0.85; 95% confidence interval (CI), 0.76-0.96] and sub-scores in the verbal fluency test (animals, vegetables, and fruits). The presence of at least 1 complication was an independent factor predictive of a decreased lifespan (HR, 5.55; 95% CI, 1.91-16.13). In AD patients, presence of complications was an indicator of poor survival, while good performance in assessments of executive function, such as the verbal fluency test and Stroop test, at baseline was associated with longer survival.