Gamma glutamyltransferase and risk of dementia in prediabetes and diabetes.

Diabetes is associated with cognitive impairment and greater risk for dementia, but the role of gamma-glutamyltransferase (γ-GT) in dementia has not been elucidated. We determined incident dementia including Alzheimer's disease and vascular dementia, analyzing data from participants aged 40 years or older in the National Health Insurance Database, collected by the National Health Insurance Service in Korea, from January 2009 to December 2015. During a median follow-up of 7.6 years, 272,657 participants were diagnosed as having dementia. Higher serum γ-GT was associated with increased risk of dementia (HR = 1.22, 95% CI = 1.20-1.24), and had a strong positive association with early onset dementia (HR = 1.32, 95% CI = 1.24-1.40). An additive impact of higher γ-GT on dementia was observed regardless of glycemic status, and prevalent diabetes with the highest γ-GT quartile had a 1.8-fold increased dementia risk (HR = 1.82, 95% CI = 1.78-1.85). This effect of γ-GT concentration in diabetes was more prominent in individuals with vascular dementia (HR = 1.94, 95% CI = 1.84-2.04). In subgroup analysis, young age, male sex, and relatively healthy subjects with a higher γ-GT quartile had more increased dementia risk. In conclusion, γ-GT concentration as well as glycemic status could be a future risk factor for dementia in the general population.

High rates of undiagnosed vascular cognitive impairment among American Indian veterans.

As data on prevalence and etiology of dementia in American Indians are limited, we sought to determine rates and patterns of memory loss among American Indian veterans with vascular risk factors. Sixty consecutive outpatient American Indian veterans with a mean age of 64 years (range 50-86), without prior dementia or mild cognitive impairment (MCI), and with ≥ 2 vascular risk factors were enrolled. The Montreal Cognitive Assessment (MoCA) and the Beck Depression Inventory-II were used to screen for cognitive impairment and depression. Patients with MoCA scores < 26 were referred for additional evaluation, including imaging, serology, and neuropsychological testing. Overall rates, types, and distribution of cognitive impairment were determined. Most prevalent vascular risk factors included hypertension (92%), hyperlipidemia (88%), diabetes (47%), and smoking (78%). Eight patients (13%) with severe depression were excluded, leaving 23/52 with abnormal MoCA scores (44%, 95%CI 30%-59%). Fifteen completed additional evaluation for memory loss, including four with normal MoCA scores who requested evaluation based on symptoms. Results were adjudicated as normal (4), non-amnestic MCI (4), vascular MCI (5), and vascular dementia (2). These results show that rates of undiagnosed cognitive impairment among American Indian veterans with vascular risk factors exceed rates previously published in non-American Indian cohorts. The most common etiology is vascular. Our findings support the need to improve vascular risk reduction in this understudied population.

[Screening and diagnostic framework of vascular dementia in Chinese population].

For lack of cognitive screening standard system and controversy over the value of imaging for cerebrovascular diseases in China, the research group of Alzheimer's Disease Chinese (ADC) studied the knowledge of neuropsychology, neuroimaging and clinical neurology, systematically reviewed the diagnostic techniques such as memory, language, visuospatial, executive, function, and magnetic resonance imaging (MRI) of cerebrovascular diseases, and their optimal threshold and diagnostic value for vascular dementia. Via a consensus meeting, the diagnostic guidelines and practical screening process are combined to construct a framework in Chinese population, which is based on the objective evidence of medical history and clinical evaluation. The diagnosis of vascular dementia is supported by imaging evidence of cerebrovascular diseases and differentiates from other causes of dementia or comorbidities. This consensus is applicable to medical units in China, and is of great significance for early detection, early diagnosis and early treatment of vascular dementia.

Apolipoprotein E gene variants of Alzheimer's disease and vascular dementia patients in a community population of Nanking.

To explore apolipoprotein E gene variants distribution among the patients of Alzheimer's disease and vascular dementia for the elderly community population in Nanking, the polymerase chain reaction and restriction fragment length polymorphism techniques were employed to analyze the gene frequency of apolipoprotein E (ApoE) for 113 cases with Alzheimer's disease (AD), 85 cases with vascular dementia (VaD), 147 cases with questionable dementia (QD), and 396 dementia-free controls. It was found that ApoE ε4 gene container (37.17%) and allele frequency (21.24 ± 2.72) of ApoE ε4 in AD group were significantly higher than those in both control and VaD group (p < 0.05). With the increment of ε4 gene dose, the incidence of the AD was significantly increased. Compared with the control group, ApoE ε4 had risk ratio (RR) of 1.82 to develop AD (p = 4e-4), and attributable risk percentage (ARP) of 45%. These results suggest that ApoE ε4 gene may be responsible for up to 45% of the genetic component of Alzheimer's disease, and may act as a discriminator between AD and VaD as well.

Absence of A673T amyloid-ß precursor protein variant in Alzheimer's disease and other neurological diseases.

The rare variant A673T in the amyloid-ß precursor protein (APP) gene has been shown to reduce the risk of cognitive impairment. We genotyped the variant in 8721 Asian individuals comprising 552 with Alzheimer's disease and vascular dementia, 790 with Parkinson's disease, and 7379 controls. The A673T variant was absent in all of the subjects. Our finding suggests that the A673T protective variant is not relevant in our Asian population. Studies in other ethnic populations would clarify whether this variant is specific to specific races/ethnicities.

Multicentre population-based dementia prevalence survey in Japan: a preliminary report.

Community-based surveys were performed in seven rural areas in Japan to investigate the prevalence of dementia and illnesses causing dementia. A total of 5431 elderly subjects were selected based on census data from 1 October 2009. In total, 3394 participants were examined (participation rate: 62.5%), and 768 dementia cases and 529 mild cognitive impairment cases were identified. Of the illnesses causing dementia, Alzheimer's disease was the most frequent (67.4%), followed by vascular dementia (18.9%), dementia with Lewy body disease (4.6%), mixed dementia (4.2%) and other illnesses. The prevalence of dementia according to 5-year age strata between 65 and 99 years was 5.8-77.7% among the participants. The prevalence of dementia in this study was higher than in previous reports in Japan and other countries. To verify the upward trend of dementia prevalence and its background factors, we have scheduled surveys for three other urban areas in 2011-2012.

Genetic association of the gene encoding RPGRIP1L with susceptibility to vascular dementia.

A previous genome-wide association study (GWAS) failed to discover any nucleotide sequence variant associated with susceptibility to vascular dementia (VaD) and remained a problem of false negatives produced by a low statistical power. The current study was conducted to identify such potential false negatives and to provide comprehensive evidence for the most plausible predisposing genetic factor using large-scale Korean cohorts. We identified the gene encoding retinitis pigmentosa GTPase regulator-interacting protein 1-like (RPGRIP1L) with multiple nucleotide variants associated with susceptibility to VaD by a modest significant threshold (P<10(-4)). Genetic associations were intensively examined with its sequence variants using 207 VaD patients and 207 age- and gender-matched control subjects. Genetic association analysis with dense variants in the region associated with VaD revealed 3 variants (P<0.0017) in strong linkage. Further analysis with VaD-related phenotypes using Korean Association REsource (KARE) cohort data showed that the region of the gene was associated with alanine aminotransferase (ALT), aspartate aminotransferase (AST), and blood pressure (BP) (P<7.6×10(-4)). The current study provided the first evidence of the association between RPGRIP1L gene and susceptibility of VaD. Functional studies are needed to understand underlying biological mechanism of the genetic association.

Roles of the tau gene short tandem repeats in late-onset Alzheimer's disease.

This study assessed the roles of Tau gene short tandem repeats (STRs) nested within intron 1 (rs5820604 and rs10675722) and Apolipoprotein E (ApoE) gene polymorphisms in 70 late-onset Alzheimer's disease (AD) subjects, 70 vascular dementia (VD) subjects, and 70 normal controls (NCs) in Guizhou Han population. Our data suggest that the Tau gene STR loci rs5820604 (CA)(19) allele may increase the risk of AD, whereas the (CA)(16) allele may be protective. The Tau gene STR loci rs10675722 (TA)(17) allele may increase the risk for AD and VD. In addition, a synergistic effect of polymorphisms in ApoE ε4 and Tau gene STR loci rs5820604 (CA)(19) allele was found in the pathogenesis of AD (p = .025, OR [odds ratio] = 3.178, 95% CI [confidence interval] = 1.156-8.741).

Apolipoprotein genotype for prediction of Alzheimer's disease in older Japanese: the Hisayama Study.

OBJECTIVES: To estimate the effects of the apolipoprotein E (APOE)-ɛ4 allele on the development of dementia and to elucidate its usefulness in the risk prediction of dementia in Japanese. DESIGN: Prospective cohort study. SETTING: The Hisayama Study, in Japan. PARTICIPANTS: Five hundred twenty-three participants with deoxyribonucleic acid samples from a population of 1,073 community-dwelling participants without dementia aged 60 to 79. MEASUREMENTS: The risk estimates of the APOE-ɛ4 allele on the development of all-cause dementia, Alzheimer's disease (AD), and vascular dementia (VaD). RESULTS: During 17 years of follow-up, 136 participants developed dementia, 81 of whom had AD and 39 VaD. After adjusting for age, sex, education, smoking, alcohol intake, systolic blood pressure, use of antihypertensive agents, glycosylated hemoglobin, serum total cholesterol, body mass index, and regular exercise, the risks of all-cause dementia and AD were significantly higher in APOE-ɛ4 carriers than in noncarriers, but no such association was observed for VaD (all-cause dementia: hazard ratio (HR)=1.81, P=.004; AD: HR=3.42, P<.001; VaD: HR=1.08, P=.86). The area under the receiver operating characteristic curve was significantly greater when the APOE genotype was incorporated into a model with potential risk factors for AD (0.74 vs 0.68, P=.02). Other measures of model discrimination (net reclassification improvement: 0.18, P=.01; integrated discrimination improvement: 6.25, P<.001) also confirmed this improvement in AD risk assessment. CONCLUSION: The APOE-ɛ4 allele is a risk factor for AD in the Japanese population. Information on APOE genotype improves AD risk assessment substantially beyond a model based on potential risk factors.

Validation of the Chinese Revised Algase Wandering Scale-Community Version for persons with dementia in northern Taiwan.

OBJECTIVE: Wandering in persons with dementia is perceived as significant due to its prevalence and negative outcomes. However, lack of a validated wandering measure in Taiwan has limited scientific investigation and clinical practice. Therefore, the purpose of this study was to validate the Chinese Revised Algase Wandering Scale-Community Version (CRAWS-CV) in northern Taiwan. METHOD: For this cross-sectional study, the sample comprised 180 elders with dementia and their family caregivers (FCs). FCs responded to the CRAWS-CV in interviews with trained research assistants. RESULTS: The structure of CRAWS-CV was examined by exploratory principal component analysis with varimax rotation. This analysis derived nine factors, explaining 71.48% of variance: eloping behavior (EB), mealtime impulsivity/temporal aspects, getting lost inside the house (GLI), pacing, impulsivity, negative outcomes, random pattern (RANDOM), and getting lost outside. The total scale and subscales showed excellent internal consistency. Good construct validity was shown by significant inter-scale correlation coefficients, and significant correlations between scores on the total CRAWS-CV and its subscales with scores on the Mini-Mental State Examination and Chinese Neuropsychiatric Inventory. The receiver operating characteristic curve showed a cutoff score of 67, with sensitivity and specificity of 83.6% and 76.9%, respectively. CRAWS-CV scores were significantly different for wanderers and non-wanderers. The one-week test-retest reliability using intra-class correlation coefficients (ICCs) showed significant correlations except for the EB and RANDOM subscales. Inter-rater reliability using an ICC was significant and acceptable except for GLI. CONCLUSION: This study supports the CRAWS-CV as a valid measure of wandering in community-dwelling elders with dementia in northern Taiwan.

Coffee intake in midlife and risk of dementia and its neuropathologic correlates.

While animal data suggest a protective effect of caffeine on cognition, studies in humans remain inconsistent. We examined associations of coffee and caffeine intake in midlife with risk of dementia, its neuropathologic correlates, and cognitive impairment among 3494 men in the Honolulu-Asia Aging Study (mean age 52 at cohort entry, 1965-1968) examined for dementia in 1991-1993, including 418 decedents (1992-2004) who underwent brain autopsy. Caffeine intake was determined according to self-reported coffee, tea, and cola consumption at baseline. Logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI) for overall dementia, Alzheimer's disease (AD), vascular dementia (VaD), cognitive impairment (Cognitive Abilities Screening Instrument score <74), and neuropathologic lesions at death (Alzheimer lesions, microvascular ischemic lesions, cortical Lewy bodies, hippocampal sclerosis, generalized atrophy), according to coffee and caffeine intake. Dementia was diagnosed in 226 men (including 118 AD, 80 VaD), and cognitive impairment in 347. There were no significant associations between coffee or caffeine intake and risk of cognitive impairment, overall dementia, AD, VaD, or moderate/high levels of the individual neuropathologic lesion types. However, men in the highest quartile of caffeine intake (>/=411.0 mg/d) [corrected] were less likely than men in the lowest quartile (

Prevalence of dementia and its subtypes in an elderly urban korean population: results from the Korean Longitudinal Study on Health And Aging (KLoSHA).

BACKGROUND/AIMS: We estimated the prevalence of dementia and its major subtypes in an elderly urban Korean population. METHODS: A study population of 1,118 Korean elders was randomly sampled from the residents aged 65 years or older living in Seongnam, Korea. Standardized face-to-face interviews, and neurological and physical examinations were conducted on 714 respondents. Dementia was diagnosed according to the DSM-IV diagnostic criteria, and its subtypes were determined according to the criteria of the NINCDS-ADRDA, the NINDS-AIREN, and the consensus guideline proposed by McKeith et al. [Neurology 1996;47:1113-1124]. RESULTS: The estimated age- and gender-standardized prevalences were 6.3% for dementia (95% CI = 4.5-8.1), 4.8% for Alzheimer's disease (AD; 95% CI = 3.3-6.4), 1.0% for vascular dementia (VD; 95% CI = 0.3-1.8), and 0.4% for dementia with Lewy bodies (DLB; 95% CI = 0.0-0.9). The prevalence of AD consistently increased with age, whereas that of VD peaked at age 75-79 years and decreased thereafter. Of the dementia patients, 72.0% were in the very mild or mild stages of the disease. CONCLUSIONS: The prevalence of dementia in a typical urban area of Korea was estimated to be 6.3%, and AD was the most prevalent subtype. DLB was less prevalent than VD among these community-dwelling Korean elders.

Lack of association between apolipoprotein E polymorphism and vascular dementia in Koreans.

To investigate an association of vascular dementia (VD) with the apolipoprotein E (APOE) polymorphism, the APOE polymorphism of 100 VD patients, 100 age- and gender-matched Alzheimer disease (AD) patients, and 200 age- and gender-matched nondemented control (NC) subjects was genotyped. The distribution of APOE polymorphism was compared. Neither the APOE epsilon4 allele nor the APOE epsilon2 allele was more prevalent in the VD patients compared with the NC subjects (P > .1 by the chi 2 test), which was the case when both men and women were analyzed separately (P > .1 by the chi2 test) and when young patients (75 years old or less) and old patients (more than 75 years old) were analyzed separately (P > .1 by the chi2 test). The estimated statistical power was over 0.80 when the odds ratios (OR) for VD conferred to the APOE epsilon4 are assumed to be higher than 2.2 and the type I error probability is set at 0.05, which is much higher than the power of the previous studies on the VD/APOE association. In conclusion, the results suggested that APOE epsilon4 allele does not confer the risk for VD, and even if it does, it does so very modestly.

Cross-cultural studies using a modified mini mental test for healthy subjects and patients with various forms of vascular dementia.

Existing neuropsychological tests are often complex and time-consuming. We designed a modified Mini Mental Test (MMT) battery for clinical assessment of the global and regional higher cortical functions of the brain. We tested its applicability in healthy subjects with different ethnic, cultural and educational backgrounds. The usefulness of our MMT as a tool for the clinical evaluation of patients with various forms of vascular dementia was determined. The MMT comprises five subtests, including clinical evaluations of: (A) orientation (6 points); (B) attention, right-left discrimination, speech, and calculation (20); (C) immediate recall, and recent and remote memory retrieval (10); (D) praxis (10); and (E) visuospatial orientation, agnosia, hemianopsia, and visual hemineglect (14). The MMT was administered to 100 healthy subjects from two different ethnic backgrounds (Indonesian and Chinese/Taiwanese) and diverse cultural and educational backgrounds, and to 61 patients with various forms of vascular dementia. MMT scores were significantly lower in healthy subjects with a low level of education regardless of their ethnic background (p<0.001). Patients with vascular dementia had much lower MMT scores than did the comparable age-adjusted normal controls (p<0.001). Of the patients with vascular dementia, those with Binswanger's disease had the lowest MMT scores (25.5+/-28.9), followed by those with large cerebral infarcts (48.0+/-7.1), cerebral haemorrhage (49.0+/-8.5), and multiple lacunar infarctions (55.0+/-0.5) (P<0.001). With a cut-off point of 33/55 (partial score/total score), the sensitivity and positive predictive value of the MMT were 0.98 and 0.94, respectively. The MMT is a simple and useful tool for clinical assessment of the cognitive functions of healthy subjects and patients with or without vascular dementia. It can be used for individuals with different ethnic, cultural and educational backgrounds.

Vascular and Alzheimer-type pathology in an autopsy study of African-Americans.

The authors studied 13 autopsy brains from a larger cohort of 270 African-Americans with a clinical diagnosis of Alzheimer disease (AD), vascular dementia (VaD), or stroke without dementia. Two subjects exhibited changes of pure VaD, 5 had pure AD, and 6 showed a mixture of AD pathology and strokes. Overall, there was good agreement between the pathologic diagnoses and the clinical diagnoses.

Ethnic variability in dementia: results from Singapore.

The diversity of Singapore's population affords a unique opportunity to study ethnic variability in the dementias. We sought to explore the effects of ethnicity on the frequency of Alzheimer disease and vascular dementia in a large Singaporean sample. A total of 357 patients were studied: 190 with vascular dementia and 167 with Alzheimer disease. Vascular dementia was more common among Chinese and Malays, whereas Alzheimer disease was more common in Indians and Eurasians. Factors that may contribute to the observed ethnic variability in dementia etiologies include differential frequency of the ApoE-e4 allele, frequency of vascular risk factors, lifestyle choices, and cultural attitudes toward health care utilization.

Progression of mild cognitive impairment to Alzheimer's or vascular dementia versus normative aging among elderly Chinese.

To compare differences in evolutionary progressions from Mild Cognitive Impairment (MCI) to dementia of Alzheimer's type (DAT) or to vascular dementia (VaD) versus normal aging, subjects identified as MCI or as cognitively normal (CN) during standard cognitive evaluations among a large epidemiological study designed to determine prevalence and incidence of dementia and its major subtypes in Beijing, China were re-examined after an interval of approximately 3 years, repeating the same investigation protocol as at baseline. MCI subjects meeting criteria for dementia and the two major subtypes, DAT and VaD were identified at follow-up evaluation. Annual conversion rates for combined dementias and for major subtypes of DAT and VaD, from MCI, were compared with conversion rates among CN subjects. Relative risks for conversion from MCI to major subtypes of dementia were also compared with CN subjects by Cox regression models. 175 MCI and 400 CN subjects were identified at baseline. Among 121 MCI subjects available at follow-up, 51 were diagnosed with dementia (29 with DAT, 18 with VaD and 4 with other dementias), compared with 14(10 DAT, 3 VaD and 1 other type dementia) diagnosed as dementia among 281 CN subjects available at follow-up. Annual conversion rates calculated from MCI to all dementias, compared with conversion rates from CNs, were 14.1% versus 1.6%. Specifically for DAT, annual conversion rates were 8.0% versus 1.1% and for VaD were 5.0% versus 0.3%. Relative risks for developing all dementias, DAT and VaD among MCI subjects were 9, 6 and 5 times greater than among CN subjects. Conversion rates among MCI subjects to dementia, and major subtypes, for elderly Chinese residents of Beijing were comparable with results reported among similar studies worldwide. Risks of developing dementia, and major subtypes, among MCI subjects in Beijing were significantly higher than among normal subjects. Identification of MCI among elderly populations provides the possibilities for dementia prevention and treatment within prodromal stages.

Influence of neuroticism, ethnicity, familism, and social support on perceived burden in dementia caregivers: pilot test of the transactional stress and social support model.

In this study we assessed the new transactional stress and social support model, postulating the role of neuroticism, ethnicity, familism, and social support in perceived burden in dementia caregivers. We used a convenience sample (N=77) of African American and White dementia caregivers. Results substantiated interrelationships among social support variables, and the influence of perceived positive social support on burden. Neuroticism was related to the perception of positive social support and burden. Results corroborated the model, focusing on neuroticism and quality of social support in modeling perceived burden in family caregivers. Findings call attention to the role of presumably long-standing individual differences in neuroticism that influence caregiver appraisals of stress and social support.