To evaluate the differential diagnostic role of apolipoprotein E (apoE) genotype in dementia, we carried out a meta- analysis of 78 case-control series, including our own new data. The dementia subjects were grouped into Alzheimer's disease (AD) and non-AD. AD patients were subgrouped according to their subtypes, and non-AD patients into vascular dementia (VD), mixed dementia (MD), and non-AD non-VD dementia (NAVD). The apoE allele frequencies and apoE genotype-specific odds ratio (OR) of each group were estimated. The (4 allele frequency was higher in all of the dementia subgroups than in the elderly controls, and the associations with (4 allele were lower in the non-AD (OR 1.8) patients than in the AD (OR 4.2) patients. However, the apoE-related risk alsovaried as a function of the subgroup, in both the AD and non-AD groups; for AD, it was dependent on the subtype of AD (OR 2.3 - 11.3), and higher in late- onset and familial cases than in early-onset and sporadic cases, respectively; among non-AD patients, it was higher in MD (OR 2.6) than in VD (OR 1.3), and intermediate in NAVD (OR 1.9), in which a significant difference was also found between Lewy body dementia (LBD) type (OR 5.1) and non-LBD type (OR 1.3). In conclusion, variability in the apoE-related risk was found in both the AD and non-AD cases, depending on the subgroup. Therefore, precise subgrouping of both AD and non-AD patients should be performed, and this information should taken into consideration when interpreting the results of apoE genotyping.
Aged ; Aged, 80 and over ; Alzheimer Disease/diagnosis/genetics ; Apolipoproteins E/*genetics ; Dementia/*diagnosis/*genetics ; Dementia, Vascular/diagnosis/genetics ; Diagnosis, Differential ; Female ; Genotype ; Human ; Male ; Middle Aged

OBJECTIVETo explore the mechanism of acupuncture in treatment of multi-infarct dementia (MID).

METHODSThe multi-infarct dementia model was made by injection of emboli into the internal carotid artery. The dementia rats were randomly divided into 3 groups: model group, acupuncture group and non-acupoint acupuncture group, and a normal group and a sham operation group were set up. The expression of CuZnSOD in the hippocampus of the rats were detected by in situ hybridization and immunohistochemical assay, and effects of acupuncture were analyzed.

RESULTSThe expressions of mRNA and protein of CuZnSOD in the hippocampus of the model group were significantly attenuated as compared with that in the normal control group. Both the parameters above were significantly increased in the acupuncture group as compared with the model control group, but with no significant difference between the acupuncture group and the normal control group.

CONCLUSIONAcupuncture can up-regulate the expressions of mRNA and protein of CuZnSOD in the rat with MID, so as to strengthen activity of antioxidase and effectively remove free radicals and improve intelligence of MID rats.

Acupuncture ; Acupuncture Therapy ; Animals ; Dementia, Multi-Infarct ; Hippocampus ; metabolism ; Humans ; RNA, Messenger ; genetics ; Rats ; Rats, Wistar

Alzheimer's disease (AD) is characterized by decreased neuronal activity and atrophy, while hyperactivity of neurons seems to make them resistant to aging and neurodegeneration, a phenomenon which we have paraphrased as 'use it or lose it'. Our hypothesis proposes that (1) during their functioning, neurons are damaged; (2) accumulation of damage that is not repaired is the basis of aging; (3) the vulnerability to AD is determined by the genetic background and the balance between the amount of damage and the efficiency of repair, and (4) by stimulating the brain, repair mechanisms are stimulated and cognitive reserve is increased, resulting in a decreased rate of aging and risk for AD. Environmental stimulating factors such as bilingualism/multilingualism, education, occupation, musical experience, physical exercise, and leisure activities have been reported to reduce the risk of dementia and decrease the rate of cognitive decline, although methodological problems are present.
Animals ; Brain ; pathology ; physiopathology ; Dementia ; genetics ; pathology ; physiopathology ; prevention & control ; Humans ; Models, Neurological

BACKGROUND: The burden of dementia is growing rapidly and has become a medical and social problem in Japan. Prospective cohort studies have been considered an effective methodology to clarify the risk factors and the etiology of dementia. We aimed to perform a large-scale dementia cohort study to elucidate environmental and genetic risk factors for dementia, as well as their interaction. METHODS: The Japan Prospective Studies Collaboration for Aging and Dementia (JPSC-AD) is a multisite, population-based prospective cohort study of dementia, which was designed to enroll approximately 10,000 community-dwelling residents aged 65 years or older from 8 sites in Japan and to follow them up prospectively for at least 5 years. Baseline exposure data, including lifestyles, medical information, diets, physical activities, blood pressure, cognitive function, blood test, brain magnetic resonance imaging (MRI), and DNA samples, were collected with a pre-specified protocol and standardized measurement methods. The primary outcome was the development of dementia and its subtypes. The diagnosis of dementia was adjudicated by an endpoint adjudication committee using standard criteria and clinical information according to the Diagnostic and Statistical Manual of Mental Disorders, 3rd Revised Edition. For brain MRI, three-dimensional acquisition of T1-weighted images was performed. Individual participant data were pooled for data analyses. RESULTS: The baseline survey was conducted from 2016 to 2018. The follow-up surveys are ongoing. A total of 11,410 individuals aged 65 years or older participated in the study. The mean age was 74.4 years, and 41.9% were male. The prevalence of dementia at baseline was 8.5% in overall participants. However, it was 16.4% among three sites where additional home visit and/or nursing home visit surveys were performed. Approximately two-thirds of dementia cases at baseline were Alzheimer's disease. CONCLUSIONS The prospective cohort data from the JPSC-AD will provide valuable insights regarding the risk factors and etiology of dementia as well as for the development of predictive models and diagnostic markers for the future onset of dementia. The findings of this study will improve our understanding of dementia and provide helpful information to establish effective preventive strategies for dementia in Japan.
Aged ; Alzheimer Disease/genetics* ; Dementia/genetics* ; Environment ; Female ; Humans ; Incidence ; Japan/epidemiology* ; Male ; Middle Aged ; Prevalence ; Prospective Studies ; Risk Factors

We report a 52-yr-old Korean woman with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) whose diagnosis was confirmed by skin biopsy and the presence of a novel mutation in the NOTCH3 gene. The patient's clinical features were rather unusual in that 1) clinical presentations were only two episodes of stroke and mild dementia unaccompanied by mood disturbances or migraine, and 2) there was no family history. Brain MRI showed T2 hyperintensities in both temporal pole areas in line with the recent suggestion by O'Sullivan et al. that the abnormality could be a radiologic marker of CADASIL. FDG-PET also showed a hypometabolism in the temporal pole areas with an abnormal finding on MRI in addition to the hypometabolism in cortical and subcortical regions. We could learn from this case that CADASIL may be included in the differential diagnoses in patients with vascular dementia associated with a small vessel disease, even in the absence of a family history, especially when there are no known stroke risk factors and when the MRI shows T2 hyperintensity in the temporal pole regions.
Amino Acid Substitution ; Biopsy ; Brain/pathology ; Codon/genetics ; Dementia, Multi-Infarct/diagnosis ; Dementia, Multi-Infarct/genetics* ; Dementia, Multi-Infarct/pathology ; Dementia, Multi-Infarct/radionuclide imaging ; Female ; Human ; Korea ; Magnetic Resonance Imaging ; Middle Aged ; Mutation, Missense* ; Neuropsychological Tests ; Point Mutation* ; Proto-Oncogene Proteins/genetics* ; Skin/pathology ; Tomography, Emission-Computed

OBJECTIVETo explore the relationship between Alzheimer's disease and its family history of the patients.

METHODSStratified analyses and logistic regression analysis were used to examine the association between Alzheimer's disease and its family history exposure in 127 cases and 254 matched controls from a population-based case-control study.

RESULTSThe risk of Alzheimer's disease was significantly higher in those who had at least one first-degree relative with dementia or major psychosis as compared to those who had no dementia or major relatives with psychosis (OR = 6.25; 8.33). Adjusted for age and level of education, family history of dementia was still associated with Alzheimer's disease positively (OR = 2.07).

CONCLUSIONThis study provides evidence that familial aggregation of Alzheimer's disease might exist among people living Beijing.

Adult ; Aged ; Aged, 80 and over ; Alzheimer Disease ; genetics ; Case-Control Studies ; China ; Dementia ; genetics ; Family Health ; Female ; Humans ; Male ; Middle Aged ; Psychotic Disorders ; genetics

This study aims to assess the expression of Klotho and insulin-like growth factor-1 (IGF-1) and the association between Klotho and IGF-1 in rats with dementia model. Thirty rats were randomly divided into three groups. Morris water maze was used to investigate the learning and memory functions, and enzyme linked immunosorbent assay was used to analyze the levels of Klotho and IGF-1. Klotho and IGF-1 levels in the model group were lower than those in other 2 groups. Morris water maze test showed that the model group had longer escape latency times and shorter step platform times compared to other groups. Line correlation model demonstrated that Klotho level was positively correlated with IGF-1 level in rats with dementia (P= 0. 029). The levels of Klotho and IGF-1 both reduced at hippocampus in rats with dementia model, suggesting that it may be a close relationship between Klotho and IGF-1 in the pathogenesis of dementia.
Animals ; Dementia ; metabolism ; Female ; Glucuronidase ; genetics ; metabolism ; Hippocampus ; metabolism ; Insulin-Like Growth Factor I ; genetics ; metabolism ; Male ; Maze Learning ; Memory ; physiology ; Rats ; Rats, Wistar

TAR DNA binding protein-43(TDP-43) and fused in sarcoma/translocated in liposarcoma protein (FUS/TLS) have been found to be associated with two neurodegenerative diseases - amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Mutations in TDP-43 and FUS/TLS lead to abnormal protein expressions, which result in altered RNA processing. The pathological changes of TDP-43 and FUS/TLS-associated ALS and FTD are similar. Although the interactions between ALS and FTD remain unknown, it is speculated that TDP-43 and FUS/TLS-associated neurodegenerative diseases may share similar pathogenesis.
Amyotrophic Lateral Sclerosis ; DNA-Binding Proteins ; genetics ; metabolism ; Frontotemporal Dementia ; Humans ; Mutation ; RNA Processing, Post-Transcriptional ; RNA-Binding Protein FUS ; genetics ; metabolism

Frontotemporal dementia (FTD) is a degenerative disease characterized by the selective frontal and temporal lobe atrophy, and progressive deficits in behavior, executive function, or language. The prevalence and incidence of FTD are 15-22/100000 and 2.7-4.1/100000, respectively, in midlife. Hereditary is an important risk factor for FTD. Although there is some controversy regarding the further syndromatic subdivision of the different types of FTD, FTD is clinically classified into behavioral variant of frontotemporal dementia, semantic dementia and progressive nonfluent aphasia. FTD can be misdiagnosed as many psychiatric disorders because of similarity of the prominent behavioral features. Advances in clinical, imaging, and molecular characterization have increased the accuracy of FTD diagnosis, thus developing for the accurate differentiation of these syndromes from psychiatric disorders. We also discuss about therapeutic strategies for symptom management of FTD. Medications such as serotonin reuptake inhibitors, antipsychotics, and other novel treatments have been used in FTD with various rates of success. Further advanced research should be directed at understanding and developing new diagnostic and therapeutic modalities to improve the FTD patients' prognosis and quality of life.
Antipsychotic Agents ; Atrophy ; Diagnosis ; Drug Therapy ; Executive Function ; Frontotemporal Dementia* ; Genetics ; Incidence ; Prevalence ; Primary Progressive Nonfluent Aphasia ; Prognosis ; Quality of Life ; Risk Factors ; Serotonin Uptake Inhibitors ; Temporal Lobe

AIMTo investigate the resting [Ca2]i level and expression of calmodulin (CaM), calmodulin-dependent protein kinase II (CaMPKII) mRNA in hippocampal neurons of the mice with vascular dementia (VD) and their roles in the pathogenesis of VD.

METHODSThe mice were subjected for ischemia/reperfusion repeatedly on bilateral common carotid arteries by knots to establish the VD models. Animals with the sham-operation were taken as control group. The changes of behavior were observed through the step-down avoidance test and water maze test on the day 29, 30 after the operations. The hippocampal neurons were obtained immediately after mice were sacrificed and the resting [Ca2+]i was measured using laser scanning confocal microscopy with Fluo-3/AM as fluorescence indicator. RT-PCR technique was used to measure the mRNA expression of CaM, CaMPKII in hippocampal neurons.

RESULTS(1) The abilities of learning and memorizing in model group were inferior to those of sham-operation group( P < 0.05). (2) The resting [Ca2]i level in model group was significantly higher than sham-operation group (P < 0.05), while the expression of CaMmRNA, CaMPKIImRNA in VD group was significantly reduced than sham-operation group (P < 0.01).

CONCLUSIONOur study indicates that excessive resting[Ca2+ ]i level and lower CaM, CaMPKII expression in hippocampal neurons might participate in the pathogenesis of VD.

Animals ; Calcium ; analysis ; Calcium-Calmodulin-Dependent Protein Kinase Type 2 ; genetics ; metabolism ; Calmodulin ; genetics ; metabolism ; Dementia, Vascular ; metabolism ; Hippocampus ; cytology ; metabolism ; Male ; Mice ; Mice, Inbred Strains ; Neurons ; metabolism ; RNA, Messenger ; genetics