Improved Mitochondrial Function in Brain Aging and Alzheimer Disease – the New Mechanism of Action of the Old Metabolic Enhancer Piracetam

Piracetam, the prototype of the so-called nootropic drugs’ is used since many years in different countries to treat cognitive impairment in aging and dementia. Findings that piracetam enhances fluidity of brain mitochondrial membranes led to the hypothesis that piracetam might improve mitochondrial function, e.g., might enhance ATP synthesis. This assumption has recently been supported by a number of observations showing enhanced mitochondrial membrane potential, enhanced ATP production, and reduced sensitivity for apoptosis in a variety of cell and animal models for aging and Alzheimer disease. As a specific consequence, substantial evidence for elevated neuronal plasticity as a specific effect of piracetam has emerged. Taken together, this new findings can explain many of the therapeutic effects of piracetam on cognition in aging and dementia as well as different situations of brain dysfunctions

An Analysis of the Public Financial Support Eligibility Rule for French Dependent Elders with Alzheimer’s Disease

AbstractBackgroundIt is crucial to define health policies that target patients with the highest needs. In France, public financial support is provided to dependent patients: it can be used to finance informal care time and nonmedical care use. Eligibility for public subsidies and reimbursement of costs is associated with a specific tool: the autonomie gérontologie groupes iso-ressources (AGGIR) scale score.ObjectiveOur objective was to explore whether patients with Alzheimer’s disease who are eligible for public financial support have greater needs than do noneligible patients.MethodsUsing data from the Dépendance des patients atteints de la maladie d’Alzheimer en France study, we calculated nonmedical care expenditures (in €) using microcosting methods and informal care time demand (hours/month) using the Resource Use in Dementia questionnaire. We measured the burden associated with informal care provision with Zarit Burden Interview. We used a modified two-part model to explore the correlation between public financial support eligibility and these three variables.ResultsWe find evidence of higher informal care use, higher informal caregivers’ burden, and higher care expenditures when patients have an AGGIR scale score corresponding to public financial support eligibility.ConclusionsThe AGGIR scale is useful to target patients with the highest costs and needs. Given our results, public subsidies could be used to further sustain informal caregivers networks by financing programs dedicated to lowering informal caregivers’ burden

Mild cognitive impairment and deficits in instrumental activities of daily living: a systematic review

Introduction: There is a growing body of evidence that subtle deficits in instrumental activities of daily living (IADL) may be present in mild cognitive impairment (MCI). However, it is not clear if there are IADL domains that are consistently affected across patients with MCI. In this systematic review, therefore, we aimed to summarize research results regarding the performance of MCI patients in specific IADL (sub)domains compared with persons who are cognitively normal and/or patients with dementia. Methods: The databases PsycINFO, PubMed and Web of Science were searched for relevant literature in December 2013. Publications from 1999 onward were considered for inclusion. Altogether, 497 articles were retrieved. Reference lists of selected articles were searched for potentially relevant articles. After screening the abstracts of these 497 articles, 37 articles were included in this review. Results: In 35 studies, IADL deficits (such as problems with medication intake, telephone use, keeping appointments, finding things at home and using everyday technology) were documented in patients with MCI. Financial capacity in patients with MCI was affected in the majority of studies. Effect sizes for group differences between patients with MCI and healthy controls were predominantly moderate to large. Performance-based instruments showed slight advantages (in terms of effect sizes) in detecting group differences in IADL functioning between patients with MCI, patients with Alzheimer’s disease and healthy controls. Conclusion: IADL requiring higher neuropsychological functioning seem to be most severely affected in patients with MCI. A reliable identification of such deficits is necessary, as patients with MCI with IADL deficits seem to have a higher risk of converting to dementia than patients with MCI without IADL deficits. The use of assessment tools specifically designed and validated for patients with MCI is therefore strongly recommended. Furthermore, the development of performance-based assessment instruments should be intensified, as they allow a valid and reliable assessment of subtle IADL deficits in MCI, even if a proxy is not available. Another important point to consider when designing new scales is the inclusion of technology-associated IADL. Novel instruments for clinical practice should be time-efficient and easy to administer

Seropositivity to Herpes Simplex Virus Antibodies and Risk of Alzheimer's Disease: A Population-Based Cohort Study

International audienceBACKGROUND: Herpes Simplex Virus (HSV) infection has been proposed as a possible risk factor of Alzheimer's Disease (AD) notably because it is neurotropic, ubiquitous in the general population and able to establish lifelong latency in the host. The fact that HSV was present in elderly subjects with AD suggests that the virus could be a co-factor of the disease. We investigated the risk of developing AD in anti-HSV immunoglobulin G (IgG) positive subjects (indicator of a lifelong infection to HSV) and IgM-positive subjects (indicator of primary infection or reactivation of the virus) in a longitudinal population-based cohort of elderly subjects living in the community. METHODS: Cox proportional hazard models were used to study the risk of developing AD according to the presence or not of anti-HSV IgG and IgM antibodies, assessed in the sera of 512 elderly initially free of dementia followed for 14 years. RESULTS: During the follow-up, 77 incident AD cases were diagnosed. Controlled for age, gender, educational level and Apolipoprotein E4 (APOE4) status, IgM-positive subjects showed a significant higher risk of developing AD (HR = 2.55; 95% CI [1.38-4.72]), although no significant increased risk was observed in IgG-positive subjects (HR = 1.67; 95%CI [0.75-3.73]). No modification effect with APOE4 status was found. CONCLUSION: Reactivation of HSV seropositivity is highly correlated with incident AD. HSV chronic infection may therefore be contributive to the progressive brain damage characteristic of AD

Recommendations for the use of Serious Games in people with Alzheimer's Disease, related disorders and frailty.

International audienceAlzheimer's disease and other related disorders (ADRD) represent a major challenge for health care systems within the aging population. It is therefore important to develop better instruments to assess the disease severity and progression, as well as to improve its treatment, stimulation, and rehabilitation. This is the underlying idea for the development of Serious Games (SG). These are digital applications specially adapted for purposes other than entertaining; such as rehabilitation, training and education. Recently, there has been an increase of interest in the use of SG targeting patients with ADRD. However, this field is completely uncharted, and the clinical, ethical, economic and research impact of the employment of SG in these target populations has never been systematically addressed. The aim of this paper is to systematically analyze the Strengths, Weaknesses, Opportunities, and Threats (SWOT) of employing SG with patients with ADRD in order to provide practical recommendations for the development and use of SG in these populations. These analyses and recommendations were gathered, commented on and validated during a 2-round workshop in the context of the 2013 Clinical Trial of Alzheimer's Disease (CTAD) conference, and endorsed by stakeholders in the field. The results revealed that SG may offer very useful tools for professionals involved in the care of patients suffering from ADRD. However, more interdisciplinary work should be done in order to create SG specifically targeting these populations. Furthermore, in order to acquire more academic and professional credibility and acceptance, it will be necessary to invest more in research targeting efficacy and feasibility. Finally, the emerging ethical challenges should be considered a priority

Fast cognitive decline at the time of dementia diagnosis: a major prognostic factor for survival in the community.

BACKGROUND/AIMS: Current findings suggest the existence of a category of fast cognitive decliners with a poorer prognosis but better treatment response. Our study aimed at confirming the concept of fast decliners at the time of Alzheimer's disease (AD) diagnosis which best predicts mortality, in an unselected sample. METHODS: 245 incident cases of AD were selected from the French longitudinal cohort PAQUID. We investigated a different threshold of cognitive decline [measured by the annual loss of points in the Mini Mental State Examination (MMSE) score] to define when a subject could be considered as a fast decliner. We used Cox proportional hazards models to study the relation between cognitive decline and mortality. RESULTS:The significant threshold of decline associated with a higher mortality rate was a loss of 3 points per year in the MMSE score. Among the 245 AD cases, 83 (33.9%) subjects were considered as fast decliners. Of them, 78.3% died during the follow-up compared with 63.0% of the slow decliners (RR = 1.7, 95% CI 1.2-2.5). CONCLUSION:These results constitute an empirical validation of the concept of fast decliners in community-based AD patients and justify the cutoff of 3 points for the definition of this condition

Predictive value of 6-month decline in ADAS-cog for survival without severe Alzheimer's disease.

International audienceBACKGROUND/AIMS: To determine the predictive value of the 6-month evolution of the ADAS-cog score in initially mild to moderate Alzheimer's disease (AD) patients on the risk of death or severe dementia (MMSE or=7 points) to the greatest cognitive improvement (gain >or=4 points). RESULTS: Among 536 AD patients, 53 (9.9%) had a 6-month decline of 7 points or more. This group with the severest deterioration was significantly associated with the risk of severe dementia or death at 2 years (relative risk, RR = 3.8, 95% confidence interval, CI = 2.1-6.8), even after adjustment for baseline MMSE, disability and ADAS-cog score (RR = 2.6, 95% CI = 1.4-5.0). In addition, subjects with a decline by at least 4 points were also at greater risk of severe dementia. CONCLUSION: These results confirm the value of the ADAS-cog scale as a judgement criterion in clinical trials since it is a good surrogate marker of long-term prognosis. The proportion of fast decliners on the ADAS-cog could be a helpful judgement criterion for future trials in AD

Gender and education impact on brain aging: A general cognitive factor approach.

This article may not exactly replicate the final version published in the APA journal. It is not the copy of record.International audienceIn cognitive aging research, the study of a general cognitive factor has been shown to have a substantial explanatory power over the study of isolated tests. The authors aimed at differentiating the impact of gender and education on global cognitive change with age from their differential impact on 4 psychometric tests using a new latent process approach, which intermediates between a single-factor longitudinal model for sum scores and an item-response theory approach for longitudinal data. The analysis was conducted on a sample of 2,228 subjects from PAQUID, a population-based cohort of older adults followed for 13 years with repeated measures of cognition. Adjusted for vascular factors, the analysis confirmed that women performed better in tests involving verbal components, while men performed better in tests involving visuospatial skills. In addition, the model suggested that women had a slightly steeper global cognitive decline with oldest age than men, even after excluding incident dementia or death. Subjects with higher education exhibited a better mean score for the 4 tests, but this difference tended to attenuate with age for tests involving a speed component. (PsycINFO Database Record (c) 2008 APA, all rights reserved)