Dementia in Swedish Twins: Predicting Incident Cases

Thirty same-sex twin pairs were identified in which both members were assessed at baseline and one twin subsequently developed dementia, at least 3 years subsequent to the baseline measurement, while the partner remained cognitively intact for at least three additional years. Eighteen of the 30 cases were diagnosed with Alzheimer’s disease. Baseline assessments, conducted when twins’ average age was 70.6 (SD = 6.8), included a mailed questionnaire and in-person testing. Which twin would develop dementia was predicted by less favorable lipid values (higher apoB, ratio of apoB to apoA1, and total cholesterol), poorer grip strength, and—to a lesser extent—higher emotionality on the EAS Temperament Scale. Given the long preclinical period that characterizes Alzheimer’s disease, these findings may suggest late life risk factors for dementia, or may reflect changes that are part of preclinical disease

Acetylsalicylic acid as an adjuvant therapy for schizophrenia

BACKGROUND: Findings from both epidemiological and basic research point to the possibility that NSAIDS impede the deterioration in schizophrenia. METHODS: To study the efficacy of acetylsalicylic acid we will perform a randomized placebo controlled double-blind add-on trial of 80 inpatients and outpatients with schizophrenia, schizophreniform or schizoaffective disorder. Patients will be 1:1 randomized to either 3 months 1000 mg acetylsalicylic acid per day or 3 months placebo, in addition to their regular antipsychotic treatment. All patients will receive pantoprazole treatment for gastroprotection. The outcomes of this study are 3-month change in psychotic and negative symptom severity, cognitive function, and several immunological parameters. This trial may (1) yield a new (adjuvant) therapy for schizophrenia and (2) add to the knowledge on the pathogenesis of this major psychiatric disorder

Study of cosolvent-induced α-chymotrypsin fibrillogenesis: Does protein surface hydrophobicity trigger early stages of aggregation reaction?

The misfolding of specific proteins is often associated with their assembly into fibrillar aggregates, commonly termed amyloid fibrils. Despite the many efforts expended to characterize amyloid formation in vitro, there is no deep knowledge about the environment (in which aggregation occurs) as well as mechanism of this type of protein aggregation. Alpha-chymotrypsin was recently driven toward amyloid aggregation by the addition of intermediate concentrations of trifluoroethanol. In the present study, approaches such as turbidimetric, thermodynamic, intrinsic fluorescence and quenching studies as well as chemical modification have been successfully used to elucidate the underlying role of hydrophobic interactions (involved in early stages of amyloid formation) in α-chymotrypsin-based experimental system. © 2009 Springer Science+Business Media, LLC

Amyloid and Tau Pathology Associations With Personality Traits, Neuropsychiatric Symptoms, and Cognitive Lifestyle in the Preclinical Phases of Sporadic and Autosomal Dominant Alzheimer's Disease

Background: Major prevention trials for Alzheimer’s disease (AD) are now focusing on multidomain lifestyle interventions. However, the exact combination of behavioral factors related to AD pathology remains unclear. In 2 cohorts of cognitively unimpaired individuals at risk of AD, we examined which combinations of personality traits, neuropsychiatric symptoms, and cognitive lifestyle (years of education or lifetime cognitive activity) related to the pathological hallmarks of AD, amyloid-β, and tau deposits. Methods: A total of 115 older adults with a parental or multiple-sibling family history of sporadic AD (PREVENT-AD [PRe-symptomatic EValuation of Experimental or Novel Treatments for AD] cohort) underwent amyloid and tau positron emission tomography and answered several questionnaires related to behavioral attributes. Separately, we studied 117 mutation carriers from the DIAN (Dominant Inherited Alzheimer Network) study group cohort with amyloid positron emission tomography and behavioral data. Using partial least squares analysis, we identified latent variables relating amyloid or tau pathology with combinations of personality traits, neuropsychiatric symptoms, and cognitive lifestyle. Results: In PREVENT-AD, lower neuroticism, neuropsychiatric burden, and higher education were associated with less amyloid deposition (p = .014). Lower neuroticism and neuropsychiatric features, along with higher measures of openness and extraversion, were related to less tau deposition (p = .006). In DIAN, lower neuropsychiatric burden and higher education were also associated with less amyloid (p = .005). The combination of these factors accounted for up to 14% of AD pathology. Conclusions: In the preclinical phase of both sporadic and autosomal dominant AD, multiple behavioral features were associated with AD pathology. These results may suggest potential pathways by which multidomain interventions might help delay AD onset or progression

Psychosis risk as a function of age at onset: A comparison between early- and late-onset psychosis in a general population sample

This paper proposes a partial-order semantics for a stochastic process algebra that supports general (non-memoryless) distributions and combines this with an approach to numerically analyse the first passage time of an event. Based on an adaptation of McMillan's complete finite prefix approach tailored to event structures and process algebra, finite representations are obtained for recursive processes. The behaviour between two events is now captured by a partial order that is mapped on a stochastic task graph, a structure amenable to numerical analysis. Our approach is supported by the (new) tool FOREST for generating the complete prefix and the (existing) tool PEPP for analysing the generated task graph. As a case study, the delay of the first resolution in the root contention phase of the IEEE 1394 serial bus protocol is analysed

Accelerated functional brain aging in pre-clinical familial Alzheimer’s disease

Resting state functional connectivity (rs-fMRI) is impaired early in persons who subsequently develop Alzheimer’s disease (AD) dementia. This impairment may be leveraged to aid investigation of the pre-clinical phase of AD. We developed a model that predicts brain age from resting state (rs)-fMRI data, and assessed whether genetic determinants of AD, as well as beta-amyloid (Aβ) pathology, can accelerate brain aging. Using data from 1340 cognitively unimpaired participants between 18–94 years of age from multiple sites, we showed that topological properties of graphs constructed from rs-fMRI can predict chronological age across the lifespan. Application of our predictive model to the context of pre-clinical AD revealed that the pre-symptomatic phase of autosomal dominant AD includes acceleration of functional brain aging. This association was stronger in individuals having significant Aβ pathology

The epidemiology of psychosis in dementia

Objective: Authors compared delusions, hallucinations, and misidentification delusions in Alzheimer disease (AD) and vascular dementia (VaD) patients. Methods: The authors report data on the prevalence, severity, clinical, and demographic associations of these symptoms in a population sample of 260 persons with dementia, examined with the Neuropsychiatric Inventory. Results: The primary finding was that there was no difference in psychosis as a whole, or in delusions and hallucinations, between AD and VaD. Also, in AD, female gender appeared to be a risk factor for delusions; subjects in an earlier stage of dementia showed fewer delusions. Conclusion: The profile of delusions and hallucinations seen is different from that seen in schizophrenia, further supporting the hypothesis that AD-associated psychosis is a distinct phenomenological syndrome

Toktrapport [24/10 - 8/11, 1977]

BACKGROUND: The substantial symptomatic overlap between depression and dementia in old age may be explained by common genetic vulnerability factors. METHODS: We investigated this idea by comparing the occurrence of both disorders in first-degree relatives of 78 patients with Alzheimer disease (AD), of 74 with late-onset depression (onset age of < or = 60 years), of 78 with early-onset depression, of 53 with comorbid lifetime diagnoses of AD/depression, and of 162 population control subjects. Diagnostic information on their 3002 relatives was obtained from structured direct assessments and from family history interviews. RESULTS: The 90-year lifetime incidence of primary progressive dementia was significantly higher in relatives of patients with AD (30%) and comorbid AD/depression (27%) than in relatives of patients with early-onset (21%) or late-onset (26%) depression, or of controls (22%) (P =.01). Lifetime incidence of depression was significantly higher in relatives of patients with early-onset depression (13%) than in relatives of patients with AD (10%) or controls (9.0%) (P =.006). Lifetime incidence of depression was similar in control relatives and in relatives of those patients with comorbid AD/depression (8.6%). Relatives of patients with late-onset depression also showed similar occurrence of depression until the age of 80 years, but the figure increased sharply thereafter to 19.1% by the age of 90 years. CONCLUSIONS: Primary progressive dementia and early-onset depression represent clinical entities with distinct inheritance. Late-onset depression does not share substantial inheritance in common with dementia or with early-onset depression, but does show modest familial clustering