HLA A2 allele is associated with age at onset of Alzheimer's disease

The prevalence of the HLA A2 allele was investigated in a group of Italian patients with sporadic and early-onset familial Alzheimer's disease (AD and FAD) to analyze the potential association of this allele with early age of onset of the disease. The possible interaction between the HLA A2 allele and apolipoprotein E epsilon4 allele was analyzed. Our data suggest that A2 and epsilon4 alleles may have additive effects on AD onset, and that A2 may play an important role in determining or contributing to a very early age at onset. These findings further support the hypothesis of the involvement of an immune/inflammatory mechanism in the pathogenesis of AD.     

Age at onset is associated with disease severity in Lewy body variant and Alzheimer's disease

This study investigated the influence of age at onset on cognitive performance, neuropathological and neurochemical features in autopsy-confirmed sporadic Lewy body variant (LBV) and in Alzheimer's disease (AD). We compared 28 early-onset (< or = 70 years) LBV subjects with 28 matched late-onset (> 70 years) subjects. Similarly, we examined the same features in 89 early onset AD and 89 matched late onset AD patients. Patients with early onset LBV and early onset AD declined more rapidly, had more neuritic plaques, and greater neocortical cholinergic loss compared to late onset LBV and late onset AD subjects. Taken together, these results suggest that for both LBV and AD, earlier age at onset may predict a more aggressive disease course.     

Early onset Alzheimer's disease in a South American pedigree from Argentina

We report the clinical, SPET, immunohistochemical and DNA features of an early-onset familial Alzheimer's disease (FAD) in an Argentine pedigree of South American indian ethnic background. Pedigree spans 5 generations comprising more than 110 biological relatives. Clinical data supported the diagnosis of early onset FAD (mean age at onset 38.9 years) in 10 family members, including 3 with pathological confirmation (mean age at death 48.5). The pattern of transmission suggested autosomal dominant inheritance. Prominent features were mood changes, early language impairment, myoclonus, seizures and cerebellar signs. SPET displayed bilateral frontal, temporo-parietal and cerebellar hypoperfusion in early stages and in an asymptomatic member at risk, suggesting that SPET may have predictive value in this family. Immunohistochemistry showed β amyloid deposits within neuritic plaques and vessel walls and no anti-PrP immunoreactivity. DNA analysis showed no abnormalities in the β amyloid precursor protein gene. The identification of additional genetic defects in well characterized independent FAD pedigrees will contribute to the understanding of the pathogenesis of Alzheimer's disease.     

Early detection and differential diagnosis of Alzheimer's disease and depression with neuropsychological tasks

The development of novel treatments for Alzheimer's disease (AD), aimed at ameliorating symptoms and modifying disease processes, increases the need for early diagnosis. Neuropsychological deficits such as poor episodic memory are a consistent feature of early-in-the-course AD, but they overlap with the cognitive impairments in other disorders such as depression, making differential diagnosis difficult. Computerised and traditional tests of memory, attention and executive function were given to four subject groups: mild AD (n = 26); questionable dementia (QD; n = 43); major depression (n = 37) and healthy controls (n = 39). A visuo-spatial associative learning test accurately distinguished AD from depressed/control subjects and revealed an apparent sub-group of QD patients who performed like AD patients. QD patients' performance correlated with the degree of subsequent global cognitive decline. Elements of contextual and cued recall may account for the task's sensitivity and specificity for AD.     

Saitohin gene is not associated with Alzheimer's disease

BACKGROUND: The deposition of tau protein in neurofibrillary tangles constitutes an important feature of many neurodegenerative disorders, including Alzheimer's disease. A polymorphic gene, saitohin (STH), nested within the tau gene (microtubule associated protein tau, MAPT), was recently identified and an association of a non-synonymous polymorphism in STH with increased risk for Alzheimer's disease was suggested. Objective and methods: To test the above hypothesis in a case-control association study of two independent white populations within Switzerland and Greece, comparing genotype and allele frequencies from 225 Alzheimer's disease patients and 144 healthy control subjects. RESULTS: No differences in allelic or genotypic distributions between Alzheimer's disease patients and controls was found in the individual samples (Swiss/Greek) or in the combined sample. Stratification for the presence of apolipoprotein E (APOE) epsilon 4 allele, sex, or age did not show significant effects in the populations studied, nor was there an effect on the age of onset. CONCLUSIONS: No evidence was found for an association of the non-synonymous polymorphism (Q7R) in STH and Alzheimer's disease. This finding is in line with earlier studies showing no association between MAPT and Alzheimer's disease.     

Early onset Alzheimer's disease - diagnosis, therapy and management

This work describes the characteristics of diagnosis, therapy and management of patients with presenile, early onset Alzheimer's disease on the basis of two case reports. The current state of knowledge regarding aetiological, pathophysiological and clinical characteristics is presented. The diagnostic procedures and differential diagnostic considerations are illustrated. The importance of the disclosure of the diagnosis is highlighted. Options for non-cognitive treatment, counselling and support are described.     

Werner helicase polymorphism is not associated with Alzheimer's disease

Alzheimer disease (AD) is the most common neurodegenerative disorder in the elderly and is also considered a progeroid genetic syndrome. The etiology of AD is complex and the mechanisms underlying its pathophysiology remains to be clarified. Werner syndrome (WS) is a rare autosomal recessive disorder characterized as a segmental progeroid syndrome. The gene (WRN) was recently identified. Its product acts as a DNA helicase and exonuclease. This study investigates the association of AD with the WRN 1367 polymorphisms in samples of 67 DA patients, 56 elderly healthy and 66 young healthy controls. DNA was isolated from blood cells, amplified by PCR and digested with PmaCI. We observed that the genotype distributions of WRN 1367 variants were within Hardy-Weinberg equilibrium in all subject samples. Furthermore, chi-square test comparison for genotype distributions and allele frequencies did not reveal any significant difference among the three groups of subjects (P>0.05). These results support the idea that these variants are not involved as a risk factor for developing AD.     

Autonomic dysfunction is associated with neuropsychological impairment in Lewy body disease

Journal of Neurology - This study aimed to analyze the association of autonomic dysfunction with cognition, depression, apathy, and fatigue in Lewy body disease (LBD). We included 61 patients [49...     

Plasma cytokines profile in older subjects with late onset Alzheimer's disease or vascular dementia

Some cytokines have been involved in the pathogenesis of late onset Alzheimer's disease (LOAD). A possible increase in plasma cytokines levels has been reported in LOAD and vascular dementia (VD), but the results of previous studies are conflicting. We evaluated the plasma levels of IL-6, TNF-alpha, IL-1beta, and IL-10 in four groups of older individuals: 60 patients with LOAD, 80 patients with VD, 40 subjects with cerebrovascular disease but without dementia (CDND), and 42 controls (C). By analysis of covariance (adjustment for age, gender, coronary heart disease, diabetes, hypertension, smoking, and alcohol consumption) we found that: *IL-1beta was higher in VD, LOAD, and CDND compared with controls (p<0.005). *TNF-alpha was higher in VD and LOAD compared to C (p<0.05), and in VD compared to LOAD (p<0.03). *IL-6 was higher in VD compared with LOAD (p<0.03). No differences in IL-10 values were found (Kruskal-Wallis, Asymp. Sig. 0.14). By logistic regression analysis, we demonstrated that high levels (defined as above the median) of IL-1beta and TNF-alpha, but not of IL-6, were associated with increased likelihood of having VD and LOAD compared to C, while high IL-6 levels were associated with a increased probability of having VD, compared with LOAD. Our study support the notion of a low-grade systemic inflammation in older patients with LOAD or VD, characterized by an increase in plasma IL-1beta and TNF-alpha levels. The high IL-6 levels found in VD might be not a specific finding, as it might come from several conditions including atherosclerosis and related vascular risk factors, comorbidity, and frailty.     

Alzheimer's disease is associated with distinctive semantic feature loss

A central topic of discussion in the exploration of semantic disturbance in Alzheimer's disease (AD) concerns the relative contribution of semantic content (e.g., semantic features) and semantic process. Studies have suggested that semantic dysfunction in AD is the result of deficits to either semantic process, semantic content or both. Studies that have supported the loss of semantic content have been criticised for their use of verbal stimuli and cognitively challenging experimental tasks. The current study used a novel version of the yes–no recognition memory task to compare the processing of distinctive and non-distinctive features in participants with AD whilst controlling the cognitive demands of the task. The task involved five conditions which denoted the relationship between the items in the test and study phase. A ‘non-distinctive’ and a ‘distinctive’ condition were included where non-distinctive and distinctive semantic features were manipulated between study and test, respectively. Task accuracy of participants with AD decreased relative to control participants when distinctive features were manipulated between the study and test phase of the experiment. There was no significant difference between groups when non-distinctive features were manipulated. These findings provide evidence to support the loss of semantic content in AD.     

The neuropsychological diagnosis of Alzheimer's disease

Neuropsychological assessment potentially subserves several functions in subjects in whom Alzheimer's disease (AD) is suspected. Such assessment can detect the presence of brain disease once significant neuronal disruption has occurred. Analysis of the pattern and evolution of cognitive deficits allows inferences to be drawn regarding the likely underlying pathology. Neuropsychological assessment enables delineation of the particular cognitive strengths and weaknesses of individual patients, facilitating the construction of individual management programs. Lastly, cognitive testing provides a cost-effective means of monitoring disease progression and the effects of treatment. This review describes the typical pattern and evolution of cognitive deficits in AD, outlines a number of variant presentations, discusses the differential diagnosis from other dementias, and addresses the issue of progression to clinically probable AD in the cognitively impaired, non-demented elderly. It is anticipated that biomarkers for AD will complement neuropsychological assessment by enabling disease detection before unequivocal cognitive deterioration has ensued, and by improving the accuracy of clinical diagnosis of dementia type. The development of reliable biomarkers will also enable improvements in the sensitivity and accuracy of neuropsychological assessment in AD to be made, more quickly and efficiently than is currently possible using longitudinal studies.     

Early neuropsychological detection and the characteristics of Parkinson's disease associated with mild dementia

Parkinson's disease (PD) may exhibit patterns of cognitive deficits, yet physicians are currently lacking operational criteria to define the clinical boundaries between PD and PD dementia (PDD). Therefore, we investigated the characteristics of the cognitive impairments in mild PDD. We recruited 30 PDD, 20 PD-MCI (PD with mild cognitive impairment without dementia) and 33 controls. All subjects were evaluated with detailed neuropsychological tests. Our results showed that visual memory, visuospatial functions, naming and calculation displayed more marked impairment than that of the other domains. Thus we suggest that adding cognitive dysfunctions of cortical type to the early cognitive deficits of PD-MCI can help predict the development of dementia.     

Deficient glutamate tranport is associated with neurodegeneration in Alzheimer's disease

The mechanisms of synapse damage in Alzheimer's disease (AD) are not fully understood. Deficient functioning of glutamate transporters might be involved in synaptic pathology and neurodegeneration by failing to clear excess glutamate at the synaptic cleft. In AD, glutamate transporter activity as assessed by D-[³H]aspartate binding is decreased; however, it is not clear to what extent it is associated with the neurodegenerative process and cognitive alterations. For this purpose, levels of D- and L-[³H]asparate binding in midfrontal cortex were correlated with synaptophysin levels, brain spectrin degradation product levels, and clinical and neuropathological indicators of AD. Compared to control brains AD brains displayed a 34% decrease in levels of D-[³H]aspartate binding, a 30% decrease in L-[³H]aspartate binding, and a 48% loss of synaptophysin immunoreactivity. Increased levels of brain spectrin degradation products correlated with a decrease in levels of D-[³H] and L-[³H]aspartate binding, and decreased levels of synaptophysin immuno-reactivity. Levels of L-[³H]asparatate binding correlated with levels of synaptophysin immunoreactivity. These results suggest that decreased glutamate transporter activiyt in AD is associated with increased excitotoxicity and neurodegeneration, supporting the possibility that abnormal functioning of this system might be involved in the pathogenesis of synaptic damage in AD.     

Isolated hallucinosis in Alzheimer's disease is associated with African-American race

OBJECTIVES: The aim of this investigation was to study the relationship between isolated hallucinosis and race in Alzheimer's disease. METHODS: This was a cross-sectional, case control study carried out at the Neuropsychiatry Service, outpatient clinic at the Johns Hopkins School of Medicine, USA. The participants were 237 community-residing patients with probable Alzheimer's disease according to NINCDS/ADRDA criteria were included in the study. 9 patients with isolated hallucinosis were compared to a control group of 228 patients who had neither delusions nor hallucinations. Patients with only delusions or both delusions and hallucinations were excluded based on prior research. Patients were assessed clinically for the presence of hallucinations using the DSM-IV glossary definitions. They were also rated on standardized measures of cognitive impairment, depression, functional impairment, and general health. RESULTS: There was a significant association between hallucinations and race in patients with Alzheimer's disease. Before adjustment for other variables, the African-American race conferred a 5.5-fold (95% CI = 1.4-21.6; p = 0.02) increased risk for isolated hallucinosis. After adjustment for multiple other variables, this risk increased further to 27.2-fold (95% CI = 1.6-457.3; p = 0.02). CONCLUSIONS: African-American patients with Alzheimer's disease are more likely to have isolated hallucinations than Caucasian patients even after statistical adjustment for multiple confounding variables, which might distort this association. This finding has implications for our understanding of the etio-pathogenesis of hallucinations in Alzheimer's disease and for meeting health service needs of African-American patients.