S-100B and tau protein have a high differential diagnostic potential for the diagnosis of Creutzfeldt-Jakob disease (CJD). So far there has been only limited information available about the dynamics of these parameters in the cerebrospinal fluid (CSF). However, there is a special interest in finding biochemical markers to monitor disease progression for differential diagnosis and treatment.
We analyzed CSF of 45 patients with CJD and of 45 patients with other neurological diseases for tau protein and S-100B in a follow-up setting. All diagnoses of CJD were later neuropathologically verified. A ratio between tau protein differences and the time between lumbar puncture was calculated. The same was done for S-100B.
Tau protein levels of 34 cases were above the cut-off level for CJD (>1,300 pg/ml) in the first CSF sample. In 7 of 11 patients with lower tau levels in the first CSF sample, tau levels rose. The above-mentioned ratio was significantly higher in the CJD group than in the group with other neurological diseases. Similar results were obtained for S-100B.
We conclude that follow-up investigations and calculation of ratios is a useful tool in the differential diagnosis of CJD. Variations in this pattern were observed in single cases.
The intra vitam diagnosis of dementia with Lewy bodies (DLB) is still based on clinical grounds. So far no technical investigations have been available to support this diagnosis. As for tau protein and beta-amyloid(1-42) (Abeta42), promising results for the diagnosis of Alzheimer's disease (AD) have been reported; we evaluated these markers and S-100B protein in cerebrospinal fluid (CSF), using a set of commercially available assays, of 71 patients with DLB, 67 patients with AD and 41 nondemented controls (NDC) for their differential diagnostic relevance. Patients with DLB showed significantly lower tau protein values compared to AD but with a high overlap of values. More prominent differences were observed in the comparison of DLB patients with all three clinical core features and AD patients. Abeta42 levels were decreased in the DLB and AD groups versus NDC, without significant subgroup differences. S-100B levels were not significantly different between the groups. Tau protein levels in CSF may contribute to the clinical distinction between DLB and AD, but the value of the markers is still limited especially due to mixed pathology. We conclude that more specific markers have to be established for the differentiation of these diseases.
Neuropsychiatric symptoms (NPS) of Alzheimer's disease (AD) occur throughout the course of AD. Behaviors include mood alterations, psychosis, agitation, and apathy. These symptoms are a major cause of diminished quality of life for both patients and caregivers. Evidence suggests that a cholinergic deficit resulting from a loss of cholinergic neurons is the biological basis of some NPS in AD and related dementias. The basal forebrain nuclei, the primary source of cholinergic projections to the cortex, become atrophied in AD. Cholinesterase inhibitors (ChE-Is) enhance neuronal transmission by increasing the availability of acetylcholine at the receptors. This effect is believed to be beneficial in improving or stabilizing many behavioral symptoms of AD. Preliminary studies of ChE-Is have shown mixed results; however, the results of more recent studies have been favorable.
To review major trials of ChE-Is and summarize effects on behavioral symptoms. Agents reviewed include donepezil, galantamine, rivastigmine, tacrine, and metrifonate.
The review of the studies favors a benefit of the ChE-Is in reducing NPS. Of the three agents in current use, studies of all showed significant benefit in AD. Most studies showed a positive trend toward reduction of NPS on a scaled measuring tool in the treatment group even if statistical significance was not reached. In some studies, specific behavioral symptoms, particularly apathy and hallucinations, were reduced.
Evidence suggests that ChE-Is have psychotropic effects and may be of value in managing neuropsychiatric behavioral symptoms in AD. Further studies will be necessary to fully understand the potential of these agents.
AL-108-211 was a placebo-controlled, ascending-dose study that explored the safety, tolerability and efficacy of 12 weeks of treatment with AL-108 in subjects with amnestic mild cognitive impairment.
A total of 144 subjects were randomized in a 2:1 drug:placebo ratio. Subjects were enrolled into the low-dose group or placebo and then to the high-dose group or placebo. Pooling of the placebo groups yielded 3 groups (approx. 48/group) whose baseline demographics and disease characteristics were well matched.
AL-108 was generally safe and well tolerated. Analyses of efficacy data failed to detect a statistically significant difference between the treatment groups on the composite cognitive memory score. Analyses of the individual cognitive tasks identified signals of potential efficacy in 2 tests of memory and attention.
These data suggest that AL-108 was generally safe, well tolerated and merits additional investigation as a treatment for Alzheimer's disease.
In mild cognitive impairment (MCI), Alzheimer's disease (AD)-type cerebrospinal fluid (CSF) biomarker profiles predict rapid progression and conversion to AD. An increased brain amyloid burden in AD and MCI has been demonstrated with PET using [(11)C]PIB (Pittsburgh compound B). Little is known about the relationship between these biomarkers in MCI.
We studied 15 patients with amnestic MCI and 22 controls with PET using [(11)C]PIB. In MCI patients, CSF levels of Abeta42, pTAU, totalTAU and the Abeta42/pTAU ratio were measured.
In MCI patients, CSF Abeta42 was abnormal in 53% of patients, totalTAU in 67%, pTAU in 64% and the Abeta42/pTAU ratio in 64%. A composite neocortical [(11)C]PIB uptake score was increased in 87% of the MCI patients. Only 54% of [(11)C]PIB-positive subjects showed AD-type Abeta42 values. During a 2-year follow-up, 6 MCI patients converted to AD, all of them had increased neocortical PIB scores at the MCI stage. Abnormal CSF Abeta42 was found in 3 patients, pTAU in 3 patients and Abeta42/pTAU ratio in 4 patients.
Follow-up studies are needed to confirm whether [(11)C]PIB uptake might be more sensitive than CSF Abeta42 concentration in detecting increased amyloid burden in MCI, as suggested by the results of this study.
To determine early brain changes in the distribution of an amyloid positron emission tomography (PET) probe, (11)C-labeled BF-227 or [(11)C]BF-227, in order to accurately predict the progression of mild cognitive impairment (MCI) to Alzheimer's disease (AD).
Amyloid plaque burden was evaluated using [(11)C]BF-227 PET in AD, MCI and aged normal controls. A voxel-based analysis of [(11)C]BF-227 PET images was performed to characterize the culprit brain lesion in patients with MCI who were destined to progress to AD, referred to as MCI converters (MCI-C). In addition, binding characteristics of BF-227 to amyloid deposits were examined using postmortem AD brain samples.
Voxel-based statistical analyses of the BF-227 PET images clearly demonstrated an abnormal distribution of BF-227 mainly in the posterior association area in MCI-C and patients with AD. BF-227 uptake in the lateral temporal cortex was consistently observed in almost all MCI-C and patients with AD, and it distinguished MCI-C from MCI nonconverters. BF-227 binding strongly correlated with dense amyloid-β protein plaque density, but not with diffuse plaque density in the frontal cortex.
BF-227 uptake in the lateral temporal cortex is a reliable indicator that can be used for predicting prognosis in patients with MCI.
The applicability of category verbal fluency test (VFT) as a screening test for Alzheimer's disease (AD) in the Chinese population was studied.
VFTs with categories of 'animal', 'fruit' and 'vegetable' were administrated to 72 subjects with AD and 81 aged-matched, community-dwelling, non-demented elderly (NC) in Hong Kong.
A significant difference in VFT scores between NC and AD groups was found (t-test, p < 0.05). CMMSE scores were significantly correlated with VFT performances in both subject groups. The correlation of combined VFT scores with age and educational level was significant only in the NC group (Pearson correlation, p < 0.05). At a cut-off score of 24/25, the sensitivity and specificity of the VFT in screening of dementia were 86.8 and 93.4% for subjects with no formal education. For literate subjects, an optimal cut-off score of 31/32 was identified across different educational levels.
Although VFT performance was influenced by demographic factors like age and education, cognitive function was the most determining factor. With easy administration and satisfactory sensitivity and specificity, VFT is a useful and quick clinical screening test for AD in Chinese elderly.
Reduction in cardiac (123)I-metaiodobenzylguanidine (MIBG) uptake is a characteristic feature of Parkinson's disease (PD) and dementia with Lewy bodies (DLB), and is useful in distinguishing them from other neurodegenerative disorders. The aim of this study was to investigate the role of this method of scintigraphy in the differential diagnosis of dementia in our Memory Clinic. We performed MIBG scintigraphy in patients with dementia referred to the Memory Clinic and compared the heart-to-mediastinum (H/M) ratio of MIBG uptake. Thirty out of 32 patients with DLB and all 9 PD with dementia patients had reduced H/M ratios, whereas 37 out of 40 patients with Alzheimer's disease had normal H/M ratios. Most patients with vascular dementia, frontotemporal dementia, and other dementias had normal H/M ratios. The overall sensitivity to positively identify patients with Lewy body disease (including DLB and PD with dementia) was 95%, and the specificity to distinguish them from patients with other types of dementias was 87%. MIBG scintigraphy showed a high sensitivity for the detection of Lewy body disease, and also a high specificity for discrimination from other types of dementia. The scintigraphy may provide a valuable and adjunctive method in the diagnosis of Lewy body disease and a differential diagnostic tool for patients with dementias.
We assessed the role of the APOE genotype and prion protein polymorphism at codon 129 in predicting the clinical duration of 92 neuropathologically confirmed sporadic Alzheimer's disease patients. Analyses of survival showed that the absence of the APOE epsilon 4 allele in heterozygous codon 129 PRNP carriers is a negative predictor of survival. When this subgroup of patients was stratified by sex, the effect of APOE was observed in women, but not in men.
The subject presented with intellectual decline followed by progressive muscle weakness of the bilateral upper limbs when he was 60 years old. He had a point mutation (methionin-valine) at 129 prion protein codon. He died at the age of 63 and necropsy revealed bilateral frontal lobe atrophy. The frontal cortex showed neuronal cell loss in layers II and III with spongiform change. Reusche silver impregnation technique for beta-peptide combined with ubiquitin immunostaining revealed perineuronal structures encircling degenerated neurons and ubiquitin-immunoreactive (IR) dot-like deposits. They were distributed particularly in the temporal neocortex and entorhinal cortex. They differed from either classic senile or diffuse plaque by the absence of amyloid core in the center and of amyloid fibrils. Ubiquitin-IR materials were also found as neuronal inclusions in the hippocampal granular cells. Nigral degeneration and neuronal loss in the hypoglossal nerve nucleus and in the anterior horn of the spinal cord were also found and spinal cord motoneurons had Bunina body inclusions. The clinical features and pathological findings were consistent with non-Alzheimer dementia with status spongiosus and neuronal cell loss. The unusual perineuronal structures found in our case might be a specific cellular pathology of dementia of the frontal lobe type.
Polymorphisms of the prion protein gene (PRNP) are known to cause a strong susceptibility to the occurrence of prion diseases, such as Creutzfeldt-Jakob disease, and might be associated with other neurodegenerative disorders. However, an association between PRNP polymorphisms and vascular dementia (VaD) has not been reported thus far.
To investigate whether the PRNP polymorphisms are associated with an increased risk for developing VaD in the Korean population.
We compared the genotype, allele and haplotype frequencies of PRNP polymorphisms in 160 VaD patients with those in 236 healthy Koreans.
Codon 129 (M129V) and 219 (Q219K) polymorphisms in Korean VaD patients were found in the open reading frame of PRNP. Our study shows that there is no significant difference in the genotype, allele and haplotype frequencies of PRNP codon 129 and 219 polymorphisms between Korean VaD patients and normal controls. This was the first genetic association study of the polymorphisms of PRNP with VaD.
Fatal familial insomnia (FFI) and genetic Creutzfeldt-Jakob disease (CJD(D178N,)(129V)) are two phenotypes that share a common point mutation at codon 178 of the prion protein gene (PRNP), but differ in their polymorphism at codon 129 of the mutant allele. A mutation at codon 171 of the PRNP gene has been described in a family with a strong psychiatric history without prion disease.
Clinical and genetic information of a family with CJD was obtained from medical records and family informants.
We identified an African-American family with molecular and genetically confirmed CJD(D178N,)(129V) that also carried the N171S, 129V polymorphism and had a strong psychiatric clinical presentation.
This is a complex family that carries the D178N, 129V and N171S, 129V genotype. This report is the first description of both genotypes occurring within a family with genetic human prion disease.
Recent linkage and association studies have implicated the chromosome 12p13 locus as possibly harboring genetic variants predisposed to Alzheimer's disease (AD). We attempted to replicate this association in a Chinese data set comprised of 256 AD cases and 264 age-matched normal controls. A total of 14 single nucleotide polymorphisms (SNPs) were examined. Single marker association revealed the two SNPs in NCAPD2 (rs7311174 and rs2072374) as showing nominal significant p values (p = 0.0491 and 0.0116, respectively). Haplotype analysis found LD block one to be significantly associated with AD (global p = 0.0250). Haplotypes CGGATG and CAGTCG were also significantly associated with AD (p = 0.0498 and p = 0.0482, respectively). These genetic analyses provide evidence that the chromosome 12p13 locus is associated with AD in Chinese.
We obtained follow-up data on 22 sets of twins where at least one twin had Alzheimer's disease (AD). The concordance rate for monozygotic twins (n = 17 pairs) was 59%, whereas that for dizygotic twins was 40%. In our series 8 monozygotic twins had hysterectomies; all had AD. The twins with hysterectomies also had a tendency to develop AD at an earlier age than their co-twin. Five twins with serious systemic infection developed AD, and they tended to have earlier onset than their corresponding twin. We found no strong evidence that head injury predisposed to AD.
To identify prognostic factors associated with functional outcome at 13 months in a sample of stroke rehabilitation patients. Specifically, we hypothesized that cognitive functioning early after stroke would predict long-term functional outcome independently of other factors.
163 stroke rehabilitation patients underwent a structured neuropsychological examination 2-3 weeks after hospital admittance, and their functional status was subsequently evaluated 13 months later with the modified Rankin Scale (mRS) as outcome measure. Three predictive models were built using linear regression analyses: a biological model (sociodemographics, apolipoprotein E genotype, prestroke vascular factors, lesion characteristics and neurological stroke-related impairment); a functional model (pre- and early post-stroke cognitive functioning, personal and instrumental activities of daily living, ADL, and depressive symptoms), and a combined model (including significant variables, with p value <0.05, from the biological and functional models).
A combined model of 4 variables best predicted long-term functional outcome with explained variance of 49%: neurological impairment (National Institute of Health Stroke Scale; β = 0.402, p < 0.001), age (β = 0.233, p = 0.001), post-stroke cognitive functioning (Repeatable Battery of Neuropsychological Status, RBANS; β = -0.248, p = 0.001) and prestroke personal ADL (Barthel Index; β = -0.217, p = 0.002). Further linear regression analyses of which RBANS indexes and subtests best predicted long-term functional outcome showed that Coding (β = -0.484, p < 0.001) and Figure Copy (β = -0.233, p = 0.002) raw scores at baseline explained 42% of the variance in mRS scores at follow-up.
Early post-stroke cognitive functioning as measured by the RBANS is a significant and independent predictor of long-term functional post-stroke outcome.
This study examines the associations between education, cerebral perfusion, and cognitive test performance among 132 patients with Alzheimer's disease. The participants had had between 0 and 19 years of formal schooling, and had either mild or moderate dementia according to the Clinical Dementia Rating Scale. Cerebral perfusion was evaluated by the (99m)Tc-hexamethylpropylene amine oxime single photon emission computed tomography. The Mini-Mental State Examination and the Cognitive Abilities Screening Instrument were used to assess cognitive performance. For patients at each clinical dementia severity level, statistical parametric mapping was used to examine voxel by voxel the association between education and cerebral perfusion, and Pearson's correlation coefficients were calculated between education and cognitive test scores. Years of formal schooling had negative associations with cerebral perfusion and positive associations with cognitive test scores. The brain regions showing a significant education effect on perfusion involved bilateral posterior association areas in mild dementia, and bilateral parieto-temporo-frontal areas in moderate dementia. The present findings indicate that the cognitive reserve effect starts at the low end of the education range. They also suggest that the main effect of more education is a more facile use of alternative brain circuits instead of locally increased synaptic connections.
The apolipoprotein E (APOE) gene epsilon 4 allele is known to be associated with late-onset familial and sporadic Alzheimer's disease (AD). We assessed the possible relationship between APOE genotypes and morphological or functional changes in AD brains by x-ray computed tomography (CT), magnetic resonance imaging (MRI) and Xe-133 single photon emission CT (SPECT). First, we estimated the change in size of the whole brain and total ventricular system by using two x-ray CT indices, the cerebral index (CI) and ventricular index (VI), respectively. Neither CI nor VI differed significantly among APOE genotypes. Then, we focused on the inferior temporal lobe regions by introducing new MRI indices, the inferior temporal index (ITI), temporal horn index (THI) and infero-medial temporal index (IMTI). We found a significant difference in each MRI index among APOE subgroups; ITI and IMTI were lower, while THI was higher in AD patients with at least one APOE epsilon 4 allele (epsilon 4+ group) than in those without such an allele (epsilon 4-group). Finally, we compared relative regional cerebral blood flow (rCBF) of Xe-133 SPECT among the AD subgroups. Relative rCBF in the cerebral cortex, particularly in the temporal lobe, was lower in the epsilon 4+ group than in the epsilon 4- group. These results indicate that possession, and thus expression, of the APOE epsilon 4 allele affects preferentially the inferior temporal lobe, encompassing the hippocampus and amygdala, in AD patients.
Abnormal tau hyperphosphorylation has been suggested as being one of the central events in the development of neurofibrillary tangles, which are one of the characteristic neuropathological lesions found in Alzheimer's disease (AD) brains. 14-3-3 zeta protein is associated with tau in brain and stimulates tau phosphorylation. In a case-control study in 293 AD patients and 396 healthy controls, we examined whether the combined gene effects between 14-3-3 zeta (intron 4, rs 983583) polymorphism and tau (intron 9, rs 2471738) polymorphism might be responsible for susceptibility to AD. Subjects carrying both the 14-3-3 zeta (intron 4, rs 983583) AA and the tau (intron 9, rs 2471738) CC genotypes had a two and a half times lower risk of developing AD than subjects without these risk genotypes (OR = 0.4, 95% CI = 0.2-0.8, p = 0.016). Considering synergistic effects between polymorphisms in tau phosphorylation related genes may help in determining the risk profile for AD.
We explored simultaneously 14-3-3 protein, neuron-specific enolase (NSE), and one astroglial protein, S-100, recently proposed as Creutzfeld-Jakob disease (CJD) markers, in the cerebrospinal fluid (CSF) of 129 patients with suspected CJD. Cutoff values for NSE and S-100 were established at 25 and 2.5 ng/ml, respectively. The highest sensitivity was observed for S-100 (94.2%) followed by 14-3-3 (89.8%) and NSE (79.7%), while the highest specificity in CJD diagnosis was obtained with 14-3-3 protein (100%) as compared with NSE (91.5%) and S-100 (85.4%). No influence of sex, genotype at codon 129 of the prion protein gene, time between sampling, and death or disease duration has been found. Based on 90 cases initially referred as 'probable' or 'possible' CJD, with 14-3-3, NSE, or S-100 we could correctly discriminate between 'CJD' or 'non-CJD' categories in 94.4, 86.5, and 90% of the cases, respectively. When limited to 'possible CJD' cases, diagnosis based on one of the three CSF proteins was accurate in 98, 90.7 and 87.3%, respectively. In view of the fact that the CSF 14-3-3 protein test alone has the highest specificity and good sensitivity, it appears that there is no additional advantage at the moment to include NSE and/or S-100 protein in the exploration of clinically suspected CJD cases.
To examine the mortality of very mildly to severely demented persons compared to nondemented persons.
Participants in a randomly drawn population-based cohort study on dementia were followed for 14 years from 1992 to 2006. Participants were examined at baseline (3,065 nondemented and 234 prevalent demented), after 2 years (2,286 nondemented and 145 incident demented) and again after 5 years (1,669 nondemented and 124 new cases of dementia). Causes of death were ascertained in 884 nondemented and 286 demented participants. Survival for demented compared to nondemented persons was analyzed with the Cox proportional hazards model with time-dependent covariates adjusted for gender and age.
The hazard ratio of death (95% confidence interval) increased from 1.82 (1.55-2.14) for the very mildly demented to 9.52 (6.60-13.74) for the severely demented subjects. The demented participants died significantly more often of neurological causes other than dementia and of pneumonia than the nondemented participants. No other significant differences in causes of death were found.
Dementia increased the risk of death. Even in the very early stages of dementia the risk of death was increased.
We report the second phenotype of frontotemporal dementia and parkinsonism linked to chromosome 17 with S305N similar to Pick's disease pathology in two brothers. The brain of the older brother showed macroscopic atrophy compatible with Pick's disease, and subsequent tau gene analysis revealed heterozygous S305N mutation in exon 10 of the tau gene. Round-shaped neuronal inclusions similar to Pick's bodies were positive for phosphorylated serine 262 as well as other anti-tau antisera, which is different from immunoexpression of Pick's bodies. Ultrastructurally, these neuronal inclusions consisted of straight, randomly orientated fibrils measuring approximately 10-20 nm in width and 60-600 nm in length. This ultrastructural profile is similar to that of the first case of S305N. S305N reported here can cause another phenotype closely resembling Pick's disease.
Hereditary frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) caused by mutations in the tau gene shows a wide range in age at onset, several distinct clinical presentations, and a spectrum of tau pathology. Although the clinical and pathological phenotype often correlate with the location of the mutation, there also exists considerable interfamilial and intrafamilial phenotypical variation. Not all families with FTDP-17 do have mutations and deposition of hyperphosphorylated tau in the brain, but show ubiquitin-positive, tau-negative inclusions. Future research should focus on the role of other genetic and environmental factors in this form of FTDP-17, whereas the responsible gene defect(s) has still to be identified for hereditary FTD without tau mutations.
We describe the characteristic neuropathologic changes in chromosome-17-linked dementia. Identified cases to date demonstrate a uniform pathology consisting of neuronal loss, gliosis and vacuolization of frontal, anterior cingulate and temporal cortex and occipital association areas. Similar changes are present in substantia nigra, ventral striatum and amygdala. Hippocampus itself is spared, whereas the afferent perforant tract is consistently affected. Characteristic neuronal inclusions consisting of lattice-like neurofilaments are present in subcortical nuclei and glial cytoplasmic tau-positive inclusions are present throughout the white matter. These pathologic changes appear to be unique for chromosome-17-linked dementia.
Remarkable improvement in the life expectancy of the Indian population is expected to commensurate with the increase in number of dementia cases. Among various types of dementia, Alzheimer's disease (AD) and vascular dementia (VaD) are common and widely studied. We evaluated the role of apolipoprotein E (ApoE) and interleukin-6 (IL-6)-174 G/C gene polymorphism along with serum IL-6 levels in AD and VaD patients.
The polymorphisms in ApoE and IL-6-174 G/C genes were assessed using RFLP. Serum IL-6 level was measured by ELISA.
The allele ε4 of the ApoE gene was found to be associated with AD and VaD patients (p < 0.05). No association of IL-6-174 G/C polymorphism was observed in AD patients, while the IL-6-174 C allele increased the odds of having VaD twofold. Regression analysis to assess possible interaction between ApoE and the IL-6-174 G/C genes revealed that presence of both the ε4 and C alleles increased the odds of having AD 13.75-fold and VaD 14.7-fold. Serum IL-6 levels did not correlate with either presence or severity of disease among AD or VaD patients.
The ApoE ε4 allele is an important genetic marker for AD and VaD. Presence of both ApoE ε4 and IL-6 C genes increases the OR of having AD and VaD markedly.
The multifunctional mitochondrial enzyme 17beta-hydroxysteroid dehydrogenase type 10 could play a role in the development of Alzheimer disease via its high-affinity binding to amyloid-beta peptides and its overexpression.
We evaluated the specificity of alterations in mRNA/enzyme expression levels in human right and left hippocampi.
We observed a trend towards right/left laterality in nondemented nonpsychotic controls; however, the degree of asymmetry was higher for mRNA when compared to enzyme expression levels. In Alzheimer disease and schizophrenia, significant shifts to left/right asymmetry were found and the changes were associated with more marked increases in mRNA/enzyme expression in the left hemisphere. On the other hand, no alterations were observed in people with multi-infarct dementia.
Our results support studies reporting an impairment of mitochondria in Alzheimer disease or schizophrenia and a higher vulnerability of the dominant hemisphere to pathological processes. Overexpression of the enzyme could be used to distinguish Alzheimer disease from multi-infarct dementia.
In this study, we aimed to compare cerebrospinal fluid (CSF) levels of total tau (t-tau), phosphorylated tau (p-tau(181)) and positron emission tomography with (18)F-fluorodeoxyglucose (FDG-PET) in the differential diagnosis of Alzheimer's disease (AD) under clinical conditions.
In a cross-sectional, blinded, single-center study, we examined a sample of 75 unselected memory clinic patients with clinical diagnoses of dementia of Alzheimer type (DAT; n = 24), amnestic mild cognitive impairment (MCI; n = 16), other dementias (n = 13) and nondemented controls (n = 22). Discriminative accuracy, sensitivity and specificity were calculated and compared using ROC analyses.
p-tau(181) and FDG-PET were comparable in separating DAT from controls (sensitivity: 67 vs. 79%; specificity: 91% for both) and patients with other dementias (sensitivity: 71 vs. 79%; specificity: 100% for both). The sensitivity of p-tau(181) in differentiating MCI patients from controls was significantly (p < 0.05) superior to that of FDG-PET (75 vs. 44%) at a comparably high specificity (82 vs. 91%); t-tau measures were less accurate in all analyses.
FDG-PET and CSF p-tau(181) levels are able to discriminate DAT in heterogeneous and unselected samples with a high accuracy. CSF p-tau(181) might be somewhat superior for a sensitive detection of patients with MCI.
The first study to validate the diagnostic value of the DemTect, a short neuropsychological screening test for dementia (8-10 min), using 18-fluoro-2-deoxy-glucose positron emission tomography (FDG-PET) in patients of a memory clinic.
DemTect results were compared to the clinical diagnosis and to FDG-PET as a reference method for the early in vivo detection of Alzheimer's disease (AD). Results: 38 patients (age 65.2 +/- 9.8 years, 16 men, 22 women) were investigated using clinical standard examination, FDG-PET, and cranial magnetic resonance imaging. According to NINCDS-ADRDA and Petersen's criteria, 18 patients had dementia of the Alzheimer type (DAT) and 13 patients received the diagnosis of mild cognitive impairment (MCI). Compared to the clinical diagnosis, a DemTect cutoff score of < or =11 points demonstrated good sensitivity (83.3%) and specificity (70.0%) for the detection of DAT, whereas the best cutoff score for MCI was < or =13 points with comparable sensitivity (84.6%) and specificity (85.7%). With regard to FDG-PET, the DemTect demonstrated excellent sensitivity (93%) and low specificity (50%) for the detection of AD-typical patterns of cerebral glucose metabolism (cutoff < or =13 points).
DemTect is a favorable neuropsychological screening instrument for detecting cognitive dysfunction even in predementia stages of AD. For definite cross-sectional diagnosis, further diagnostic evaluation with higher specificity, e.g. comprehensive neuropsychological examination, FDG-PET or other biomarkers, is necessary.
We sought to identify markers of motor and nonmotor function in Parkinson's disease (PD) using advanced neuroimaging techniques in subjects with PD.
We enrolled 26 nondemented PD subjects and 12 control subjects. All subjects underwent [(18)F]fluorodeoxyglucose positron emission computed tomography (FDG-PET) and magnetic resonance imaging, and a complete neuropsychological battery.
FDG-PET of subjects with PD revealed significant metabolic elevations in the bilateral posterior lentiform nucleus, posterior cingulate, and parahippocampus, and metabolic reductions in the bilateral temporoparietal association cortex and occipital lobe versus controls. PD subjects had significant reductions in executive/attention function, memory/verbal learning, and speed of thinking, and significantly increased depression, anxiety and apathy scores compared with controls. Motor dysfunction correlated with increased metabolism in the posterior lentiform nucleus, pons, and cerebellum, and decreased metabolism in the temporoparietal lobe. Cognitive dysfunction correlated with increased posterior cingulate metabolism and decreased temporoparietal lobe metabolism. Depressive symptoms correlated with increased amygdala metabolism; anxiety scores correlated with decreased caudate metabolism, and apathy scores correlated with increased metabolism in the anterior cingulate and orbitofrontal lobe and decreased metabolism in the temporoparietal association cortex.
Our findings showed that motor, cognitive, and emotional dysfunction in PD are associated with distinct patterns of cerebral metabolic changes.
We determined cerebrospinal fluid (CSF) concentrations of amyloid-β (Aβ)(1-38), Aβ(1-40), Aβ(1-42), total tau and phospho-tau (p-tau) in order to study their differential expression in frontotemporal dementia (FTD, n = 25) and primary progressive aphasia (PPA, n = 12) as compared to Alzheimer's dementia (AD, n = 25) and nondemented controls (n = 20).
Commercially available ELISA and electrochemiluminescence methods were applied.
High CSF p-tau and low ratios of Aβ(1-42)/Aβ(1-40) and Aβ(1-42)/Aβ(1-38), respectively, were specific for AD. CSF Aβ(1-38) was reduced in FTD as compared to each of the other diagnostic groups, including PPA. CSF tau and p-tau levels were elevated in PPA as compared to FTD.
This is the first detailed report on biomarker patterns in PPA, indicating distinct CSF biomarker patterns in FTD and PPA as major subgroups of frontotemporal lobar degeneration. The diagnostic and pathophysiological implications of our results warrant further studies on larger and neuropathologically diagnosed patient populations.
The aim of this study was to examine the pattern of glucose uptake and the changes over time of metabolic deficits in patients with frontotemporal dementia (FTD).
10 patients who had received the clinical diagnosis of FTD underwent positron emission tomography scanning at the time of their first examination (baseline) and at follow-up (after 17.1 +/- 6.0 months). For statistical analysis, we used the SPM 99 software. First, we compared the data of the patients at baseline with an age-matched healthy control group. Second, we compared glucose uptake at follow-up with baseline measurements.
Compared with normal controls, FTD patients showed significant metabolic deficits primarily in frontal cortical areas, but also in the caudate nuclei and the thalami. At follow-up, a significant progression of metabolic deficit was exclusively observed in the orbitofrontal parts of the frontal lobe and in the subcortical structures.
These findings demonstrate that the clinical progression in patients with FTD is accompanied by a region-specific decline in cerebral glucose metabolism.
It is not known yet whether temporoparietal glucose hypometabolism in patients with probable Alzheimer's disease (AD) reflects disease severity or different subtypes of patients.
Twenty-five subjects with mild probable AD [NINCDS-ADRDA criteria; age 65.8 +/- 9.3 years (mean +/- SD); Mini-Mental State Examination (MMSE) 26.0 +/- 3.3] were investigated. [(18)F]FDG-PET data were analyzed visually with raters blinded to the diagnosis and with a quantitative analysis in the region of interest on individual anatomically normalized PET scans.
Thirteen of 25 patients showed temporoparietal hypometabolism on visual inspection (PET+; age 65.7 +/- 10.7), 12 patients had normal FDG-PET results (PET-; age 65.9 +/- 8.0; n.s.). The MMSE and immediate reproduction of the Wechsler Memory Scale (WMS-R-I) were 27.7 +/- 1.9 and 31.1 +/- 6.1 in the PET- vs. 24.5 +/- 3.6 (p = 0.012) and 22.0 +/- 7.4 (p = 0.006) in the PET+ group. Immediate and delayed recall in the California Verbal Learning Test and delayed reproduction in the Wechsler Memory Scale were alike. Regression analysis revealed a significant correlation of temporoparietal glucose metabolism with the block span (r = 0.60; p < 0.01) and the WMS-R-I (r = 0.68; p < 0.01) but not with measures of hippocampal function.
Temporoparietal glucose metabolism in patients with very mild AD is a sign of disease spread beyond the temporal lobe. This may aid in establishing objective parameters for future therapeutic studies.
Patients with dementia and leukoaraiosis may have either Alzheimer's disease (AD) with cerebrovascular changes or a form of vascular dementia (VaD). The presence or absence of the characteristic AD pattern of bilateral temporoparietal hypometabolism on (18)FDG-PET was used to differentiate 30 patients with progressive dementia and severe leukoaraiosis. Compared to 18 patients with the typical AD pattern (group I), the remaining 12 (group II) had better recognition memory, and greater difficulty with sustained attention and serial reversals. Better recognition memory, confluent periventricular leukoaraiosis, and poorer sustained attention distinguished all group II patients from group I. Dementia patients with severe leukoaraiosis and bilateral temporoparietal hypometabolism may have predominant AD; those who lack this pattern and have confluent leukoaraiosis may have a greater contribution from VaD. Copyrightz1999S.KargerAG,Basel
Cognitive impairment has been associated with increased mortality. Most studies, however, have only included small numbers, if at all, of the very old. In a large nationwide survey of all Danes born in 1905 and still alive in 1998, where the baseline examination was conducted, we examined the impact of cognitive impairment on mortality over a 2-year period. No cognitive impairment was defined as a score of 24-30 points on the Mini Mental State Examination, mild cognitive impairment was defined as a score of 18-23 points, and severe impairment was defined as a score of 0-17 points. Cox regression analysis was applied to adjust for a number of known and suspected factors known or suspected of being associated with cognition and mortality (e.g. sociodemographic factors, sex, smoking, alcohol consumption, depressive symptoms, and physical abilities), and yielded hazard ratios (95% confidence interval) of 1.24 (1.00-1.55) for mildly impaired and 1.73 (1.37-2.20) for severely impaired Danes compared to individuals with no impairment. Cognitive impairment predicts mortality among the very old, even after controlling for most known predictors of mortality.
Alzheimer's disease (AD) is characterized by deposition of oxidized low-density lipoprotein (LDL) forming the senile plaque and by structural changes and cell death in acetylcholine-producing neurons. Paraoxonase-1 (PON-1) is a secreted protein primarily associated with high-density lipoproteins (HDL) and participates in the prevention of LDL oxidation. PON-1 is also an arylesterase that hydrolyzes paraoxon, an active toxic metabolite of parathion, thus providing protection against organophosphate poisoning and metabolization of environmental neurotoxins that might be responsible for neurodegeneration with aging. Serum levels of PON-1 are genetically determined and strongly influenced by a common polymorphism on the position 192 of the PON-1 gene. The aim of this study was to evaluate whether the polymorphism of the PON-1 gene is associated with AD. We studied 124 Italian subjects affected by probable AD and 135 age- and sex-matched controls. The distribution of PON-1 genotypes was 64 QQ, 46 QR, 14 RR in the AD patients and 57 QQ, 59 QR, 19 RR in the control subjects. No statistically significant difference was found between the two groups in our population (p = 0.130 for homozygous QQ, p = 0.279 for heterozygous QR, and p = 0.502 for homozygous RR). These results suggest that the human Gln-Arg 192 Q/R polymorphism of the PON-1 gene is not associated with AD in an Italian population.
Previous studies used 192 IgG-saporin to study cholinergic function because of its facility for selective lesioning; however, results varied due to differences in the methods of administration and behavioral tests used. We examined an animal model of dementia using 192 IgG-saporin to confirm its features before applying this model to research of therapeutic drugs or electrical stimulation techniques.
Features were verified by the Morris water maze test, immunochemistry, and Western blotting. Animals were examined after intraventricular injection of 192 IgG-saporin (0.63 μg/μl; 6, 8, and 10 μl) or phosphate-buffered saline.
In the acquisition phase of the Morris water maze test, the latencies of the injection groups were significantly delayed, but recovered within 1 week. In the probe test, 2 of 4 indices (time in the platform zone and the number of crossings) were significantly different in the 8-μl injection group. Immunohistochemistry revealed the extent of cholinergic destruction. Activity-regulated cytoskeleton-associated protein and glutamate decarboxylase expression significantly decreased in the frontal cortex (8- and 10-μl groups), but not in the hippocampus.
Spatial memory impairment was associated with cholinergic basal forebrain injury as well as frontocortical GABAergic hypofunction and synaptic plasticity deceleration.
We examined a 65-year-old patient with clinicopathological features that met the criteria of frontotemporal dementia (FTD), particularly frontal lobe degeneration (FLD). He came from a family with concentrated occurrence of dementia symptoms in the presenium. Neuropathological examination disclosed brain atrophy locally pronounced on the frontotemporal lobes with characteristic neuronal loss, microvacuolation and astrocytic gliosis. There were no pathological hallmarks such as senile plaques, Pick bodies (PBs), achromatic cells and neurofibrillary tangles. Precise separation of FTD from Pick disease (PD) and motor neuron disease with dementia (MNDD) has not yet been established, and they are included in one spectrum. Antibodies against paired helical filament tau protein demonstrated immunopositive cytoskeletal structures within the neurons as well as the glial cells in the brain of the present case. They were selectively stained with tau 199/202 but not tau 396, which were provided newly to recognize phosphorylation at Ser 199/202 or Ser 396 in tau, respectively. We investigated tau pathology in the present case in comparison to 8 cases with PD that were clinicopathologically confirmed. Neither tau 199/202 nor tau 396 stained the CNS structures in PD cases with few PBs, while both stained evidently those as well as PBs in PD cases associated with many PBs; so that the present case could be distinguished from PD on the basis of the immunoreactivity to site-specific phosphorylated tau. Our result suggests that FTD, especially familial FLD type might involve unique tau pathology, no matter whether FLD is a distinct entity from PD, or a variant form in the wide FTD spectrum including PD and MNDD and other related disorders.
Inconsistencies in the relationship between depression and cognitive decline may exist because the expected cognitive domains at risk have not been specified in previous study designs. We aimed to examine the relationship between depressive symptoms and verbal episodic memory functioning over time.
Data from a prospective cohort study (Health and Retirement Study; 1998-2004; n = 18,465), a multistage national probability sample of older adults in the United States, were analyzed. Verbal learning and memory of a 10-word list learning task were the main outcomes. Depressive symptoms (Center for Epidemiologic Studies - Depression Scale) constituted the main predictor.
Depressive symptoms were associated with significantly lower immediate (-0.05; p < 0.001) and delayed (-0.06; p < 0.001) word list recall scores after controlling for demographics and baseline and time-varying cardiovascular disease risks and diseases.
In this US national study of older adults, elevated depressive symptoms were associated with declines in episodic learning and memory over time. These associations were little affected by the demographic or medical conditions considered in this study. The results suggest that learning and memory decline may be a long-term feature associated with depressive symptoms among the nation's older adult population.
Sterol regulatory element-binding proteins (SREBPs) are transcription factors involved in cholesterol and fatty acid synthesis. Recently, a polymorphism in the 5'-region of the SREBP-1a gene has been described to be correlated with alterations in the plasma levels of cholesterol. Consequently the relationship between this SREBP-1a gene polymorphism and Alzheimer's disease (AD) alone and in combination with the apolipoprotein E (ApoE) 4 allele was evaluated. No association between SREBP-1a polymorphism alone and AD could be seen. However, in the group of healthy ApoE4 allele carriers, the number of homozygote SREBP-1a DeltaG allele carriers was significantly higher than in AD patients. Cerebrospinal fluid levels of cholesterol were lower in AD patients who were carriers of the SREBP-1a DeltaG allele, and the ratio of 24S-hydroxycholesterol to cholesterol was increased in these probands. Our data suggest a reduced risk of AD in carriers of an ApoE4 allele who are additionally homozygous for the SREBP-1a DeltaG allele, which is possibly due to the influence of SREBP-1a polymorphism on brain cholesterol metabolism. This is the first report on a genetic factor which prevents the deleterious effect of the ApoE4 allele and thus reduces the risk of AD.
Serotonin 1A receptors (5-HT(1A)) have not been studied in dementia with Lewy bodies (DLB) or Parkinson's disease dementia (PDD) patients with depression.
To examine 5-HT(1A) in DLB and PDD postmortem in relation to depression.
[(3)H]8-hydroxy-2-dipropylaminotetralin binding to 5-HT(1A) was determined in temporal cortex (Brodmann areas, BA20 and BA36) from 10 DLB patients, 17 PDD patients and 9 controls.
5-HT(1A) density was significantly higher in BA36 in combined DLB/PDD patients with depression, but was unaltered in BA20.
Higher BA36 5-HT(1A) density in PDD and DLB patients than in control is dependent on whether the patient had experienced depression during life, not DLB/PDD diagnosis. A 5-HT(1A) antagonist adjuvant may improve treatment of depression in dementia.
Excessive release of proinflammatory cytokines by activated microglia surrounding senile plaques might contribute to the neurodegeneration associated with Alzheimer's disease (AD). Poly(ADP-ribose) polymerase 1 (PARP-1) is a nuclear protein recently implicated in the initial inflammatory response by modulating expression of inflammation-related genes, like interleukin 1 (IL-1). As PARP-1 overactivity has been shown in the AD brain, we tested the hypothesis that the PARP-1 -410 and -1672 polymorphisms would predispose people to AD due to overexpression of the PARP-1 gene, independently or in concert with the proinflammatory IL-1A -889 polymorphism. So, we performed a case-control study in 263 Spanish AD patients and 293 healthy controls. PARP-1 -410 and PARP-1 -1672 haplotypes were associated with an increased risk for AD (global haplotype association p value=0.019), and, in addition, PARP-1 haplotypes increased the risk of AD by interaction with the IL-1A -889 allele 2.
A disturbed sleep-wake rhythm cycle can be seen in delirium and as melatonin regulates this cycle via melatonin receptors, genetic variations in these receptors may contribute to susceptibility to delirium. The purpose of this study was to investigate whether genetic variants in the melatonin receptor 1B (MTNR1B) gene are associated with delirium.
Elderly medical and hip surgery patients were included in the study. Five single-nucleotide polymorphisms (SNPs) were determined in the MTNR1B gene, i.e. rs18030962, rs3781638, rs10830963, rs156244 and rs4753426.
In total, 53% of 171 hip fracture patients and 33% of 699 medical patients were diagnosed with delirium. None of the polymorphisms were found to be associated with the occurrence of delirium.
Future research could focus on sequencing this gene to look for other functional SNPs in relation to delirium.
The transcription factor LBP-1c/CP2/LSF (LBP-1c) is a candidate gene for Alzheimer's disease (AD) because it is located in a putative hotspot for an AD risk gene on chromosome 12. We investigated the effect of LBP-1c polymorphism on the risk of AD in 162 AD patients, 180 patients with major depression as hospitalized controls and 225 healthy subjects. We observed no significant association of the LBP-1c A allele with AD. Nor did we detect an interaction of the LBP-1c A allele with the apolipoprotein E4 (ApoE4) allele or the low-density lipoprotein receptor-related protein T allele which could have been related to the risk of AD. However, exploratory data analysis revealed that the LBP-1c A allele might act as a protective factor in major depression. A recent study also described an association of another gene located on chromosome 12, the mannose 6-phosphatase receptor gene, with major depression. These data suggest the presence of a putative risk gene for major depression at chromosome 12.
The polymorphism (rs1800587) in the 5'-flanking regulatory region at -889 of the interleukin-1alpha gene has been shown to be associated with inflammatory diseases and Alzheimer's disease (AD). The aim of the current study is to determine whether there is an association between the promoter region polymorphism of the interleukin-1alpha gene and late-onset AD in a cohort of Turkish patients.
One hundred and four subjects with dementia of the Alzheimer type and 103 age-matched controls were genotyped according to the PCR with confronting two-pair primers method.
Although the distribution of genotypes did not significantly differ (p = 0.107), the difference between allelic frequency was nearly significant according to a chi(2) test (p = 0.05) when the controls and patients were compared.
Our results showed that there is no association between the -889 C/T transition on the interleukin-1alpha gene and late-onset AD in the Turkish population.
Over the past few years, a number of genetic risk factors for Alzheimer's disease (AD) have been proposed. IL-1beta gene polymorphism such as IL-1beta-511 and IL-1beta+3953 have been reported to be associated with the risk of AD in a number of studies in a Caucasian population. However, conflicting results have been reported recently which showed that IL-1beta was not universally associated with the risk of AD in other populations. In order to validate these associations, we investigated the IL-1beta polymorphisms (IL-1beta-31, IL-1beta-511 and IL-1beta+3953) in a Chinese population, which has not been studied before. In our study, the allelic frequencies of IL-1beta-31C, IL-1beta-511T and IL-1beta+3953T for the AD group were 0.49, 0.57 and 0.03, respectively. The allelic frequencies of IL-1beta-31C, IL-1beta-511T and IL-1beta+3953T for the control group were 0.53, 0.61 and 0.03, respectively. No significant difference was detected in the genotypic or allelic frequencies (p > 0.25). We conclude that IL-1beta polymorphism is unlikely to be a significant risk factor for AD in the Chinese Population.
There is a lack of evidence to explain why patients with dementia are admitted to a general hospital.
Main reasons for hospitalisation were investigated in all patients admitted to a multi-ethnic general hospital during 2002-2007, by analysis of type of admission and primary diagnosis on admission. Anonymised data from the Hospital Activity Analysis Register was used to trace these patients; 505 were diagnosed with Alzheimer's disease (AD), 283 with vascular dementia (VD) and 1,773 patients were classified as unspecified dementia (UnD). Logistic regression analysis was used to compare these groups to 53,123 age-matched controls. Statistical significance of p < 0.001 was accepted.
More dementia patients were admitted as emergency cases compared to controls (AD = 95.8%, VD = 95.4%, UnD = 96.7%, controls = 54.4%; p < 0.001 for all comparisons). The proportion of patients admitted for dementia as their primary diagnosis was small (AD = 5.9%, VD = 10.6%, UnD = 6.0%). Primary diagnoses such as syncope and collapse, bronchopneumonia, urinary tract infection and dehydration were more frequent in all dementia patients than controls.
Dementia patients are frequently admitted as emergency cases, but dementia itself is often not the primary diagnosis. Earlier detection of the specific conditions mentioned above may reduce emergency hospital admissions amongst dementia patients.
Dementia disorders are today considered to be a major driver of costs in health care and social systems and worrying estimates of future dementia prevalence have been presented. It is of great interest for policy makers to have an estimate of dementia disorders' contribution to global social and health care costs, particularly in light of the demographic prognoses. The worldwide costs of dementia were estimated from prevalence figures for different regions, and cost-of-illness studies from key countries using a model based on the relationship between direct costs of care per demented and the gross domestic product per capita in each country. The worldwide direct costs for dementia in 2003 are estimated at 156 billion USD in the main scenario based on a worldwide prevalence of 27.7 million demented persons (sensitivity analysis: 129-159 billion USD). Ninety-two percent of the costs are found in the advanced economies with 38% of the prevalence. Although there are several sources of uncertainty, it is obvious that the worldwide costs are substantial and the expected increase in elderly people in the developing countries presents a great challenge.
To identify outpatient and hospital health care usage among dementia patients compared to controls.
Analysis of the French National Health Insurance general regime reimbursement database, linked to the national hospitalization database for 2007; 258,809 subjects over the age of 60 with dementia were compared to a sample of 88,296 controls.
Dementia patients more frequently had at least one annual visit to private psychiatrists and neurologists (21.9%, relative risk, RR = 7.0), nursing care (52%, RR = 1.3), physiotherapy (37%, RR = 1.45), and hospitalization (40.8%, RR = 1.7), and they less frequently consulted other private specialists (62%, RR = 0.85). Many diagnosis groups were significantly more frequent in dementia patients: nervous system (RR = 5.3), psychiatry (RR = 9.1), respiratory medicine (RR = 1.8), unspecified (RR = 2.4). Hospitalizations for endoscopy, radiotherapy, chemotherapy, and treatment of disabilities such as cataracts (RR = 0.7) were less frequent. Higher relative levels of health care use decreased with age for dementia patients.
Although the use of some forms of health care can be explained by the clinical condition induced by dementia, others must be interpreted in light of modes of medical and social management and ethical justification for screening and investigations.
A large multicenter trial of donepezil 23 mg/day versus donepezil 10 mg/day for moderate-to-severe Alzheimer's disease allowed patients taking concomitant memantine. We evaluated the efficacy/safety of donepezil 23 and 10 mg/day in this trial, with respect to concomitant memantine use.
Prespecified analysis of data from a 24-week, randomized, double-blind trial. Patients were randomized to donepezil doses (23 vs. 10 mg/day) and stratified by concomitant memantine use (yes or no). Efficacy and safety were assessed for each donepezil dose in subgroups taking or not taking concomitant memantine.
At week 24, donepezil 23 mg/day provided significant cognitive benefits over 10 mg/day (p < 0.01) on the Severe Impairment Battery, with or without concomitant memantine (ANCOVA adjusted for baseline score, country and treatment). The higher dose showed no benefit on the global function, Mini-Mental State Examination or activities of daily living measures in either memantine subgroup. Rates of treatment-emergent adverse events (AEs) were higher for donepezil 23 mg/day with memantine (80.7%) than 23 mg/day without memantine (69.7%) or 10 mg/day with/without memantine (66.7/62.0%); across all treatment groups, most events were mild/moderate in severity. Individual rates of serious AEs were low (<1.0%), regardless of concomitant memantine use.
In this population, concomitant memantine use did not alter the response profile of donepezil 23 vs. 10 mg/day. Donepezil 23 mg was generally safe and well tolerated among patients receiving donepezil alone and among patients receiving a combination of donepezil and memantine therapy.
It has been hypothesized that choline acetyltransferase (ChAT) activity might be associated with cognitive impairment in Alzheimer's disease (AD). A functional single nucleotide polymorphism (2384 G/A) of ChAT was proposed to be associated with AD risk and age of onset. The aim of this study was to evaluate this polymorphism in a cohort of Chinese AD patients and patients with mild cognitive impairment (MCI).
We conducted a case-control study in 273 cases of sporadic AD, 97 MCI patients and 271 nondemented controls from the Chinese Han population.
In AD, ChAT 2384 A carriers had a significantly earlier age of onset and worse individual cognitive function in Fuld Object-Memory Evaluation; in MCI, the carriers of both 2384 A and ApoE epsilon4 had a significantly earlier age of onset.
ChAT 2384 A allele is a risk factor for AD and MCI.