Karine Pérès

Prodromal Alzheimer's disease: Successive emergence of the clinical symptoms†

Whereas cognitive deficits are known to be detectable long before the typical symptoms of Alzheimers disease (AD) are evident, previous studies have failed to determine when cognitive functioning actually begins to decline before dementia. Utilizing the long follow‐up of the PAQUID study, we examined the emergence of the first clinical symptoms over a 14‐year period of follow‐up before the dementia phase of AD.

Fish, meat, and risk of dementia: cohort study

We obtained data from the PAQUID (Personnes Agees QUID) epidemiological study of cognitive and functional ageing (www.healthandage.net/html/min/paquid/entrance.htm). During the third wave of the study (1991-2) investigators visited 1674 people aged 68 and over without dementia and living at home in 75 parishes in southwestern France and recorded their frequency of consumption of meat and fish or seafood: daily, at least once a week (but not every day), from time to time (but not every week), never. Participants were followed up two, five, and seven years afterwards: 1416 (84.6 %) had at least one follow up visit. All the participants who had lost three points or more on the mini-mental state examination since a previous visit or were suspected of having dementia according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders , third edition, revised (DSM-III-R) were visited by a neurologist to confirm the diagnosis. We …

Natural history of decline in instrumental activities of daily living performance over the 10 years preceding the clinical diagnosis of dementia: a prospective population-based study.

OBJECTIVES: To study the subtle changes in instrumental activities of daily living (IADLs) over the 10 years preceding the clinical diagnosis of dementia.

Restriction in complex activities of daily living in MCI: impact on outcome.

Objective: To describe the restriction in instrumental activities of daily living (IADL) in mild cognitive impairment (MCI) and to assess the impact of IADL restriction on the progression to dementia and on MCI reversibility. Methods: The study sample included 1,517 participants of the PAQUID cohort, visited at 8- and 10-year follow-ups. Subjects classified as having MCI had no dementia but a cognitive deficit according to five neuropsychological tests. Four IADL (telephone, transports, medication, finances) were assessed and considered restricted if at least two of them were not performed at the highest level of performance. Cross-sectional and longitudinal analyses were conducted. Results: A total of 285 subjects were classified as having MCI at baseline, and 15.2% developed dementia within 2 years. MCI subjects were more frequently IADL restricted (34.3%) than controls (5.4%) but less than those with dementia (91.1%). The IADL-restricted MCI subjects were more likely to develop dementia over 2 years (30.7%) than the nonrestricted ones (7.8%). In multivariate analyses, the odds ratio for dementia was 7.4 (CI: 3.3 to 16.5) in the IADL-restricted MCI and 2.8 (CI: 1.3 to 6.0) in the non–IADL-restricted MCI compared with the non–IADL-restricted controls. IADL restriction also lowered the chance of reversibility to normal, observed in 10.7% of the restricted MCI and 34.7% of the nonrestricted MCI. Conclusions: Inclusion of instrumental activities of daily living restriction in the criteria of mild cognitive impairment improves the prediction of dementia and the stability of this status over time. Conversely, its exclusion results in inappropriate selection of subjects with a low probability of short-term progression to dementia.

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

Background Herpes Simplex Virus (HSV) infection has been proposed as a possible risk factor of Alzheimers 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.

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

IntroductionThere 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.MethodsThe 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.ResultsIn 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.ConclusionIADL 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.

Dementia in Subjects Aged 75 Years or Over within the PAQUID Cohort: Prevalence and Burden by Severity

Background/Aims: To analyze the prevalence of dementia by severity and to describe the sociodemographic characteristics of people with dementia in the community, as well as the consequences of this disease in terms of disability and institutionalization. Methods: This study was based on the PAQUID community-based cohort study of 1,461 subjects aged 75 years or over. Severity of dementia was assessed using the Mini-Mental State Examination (MMSE). Results: The prevalence of dementia was estimated to be 17.8%, with about 43% at a moderately severe or more severe stage of the disease (MMSE ≤ 15). About 39% of the people with dementia lived in an institution. Among the institutionalized residents, 71.6% were diagnosed as demented. About 57% of the people with dementia were ADL disabled. In this over-75 population, people with dementia accounted for 74% of the ADL-disabled subjects. The consequences of dementia were particularly frequent among the subjects who were at least at a moderately severe stage of dementia, with 59.6% of them living in institution and 87.2% being ADL disabled. Conclusion: These results confirm the high prevalence of dementia in subjects aged over 75 and illustrate the devastating consequences of this disease in terms of disability and institutionalization.

The disablement process: Factors associated with progression of disability and recovery in French elderly people

Purpose: To study the factors associated with progression, recovery and death from different grades of disability in elderly people. Method: The sample included 3198 participants of the PAQUID (‘Personnes Agées QUID’) cohort, aged 65 and over and community-dwellers at baseline. Subjects were re-interviewed 1, 3, 5, 8 and 10 years after baseline. A five-state Markov model was used to estimate transition intensities between four grades of disability and toward death. We used a hierarchic scale of disability, which combines basic and instrumental activities of daily living and mobility. Several explanatory variables were investigated: medical, personal and environmental factors. Results: The factors associated with progression and/or no recovery of disability were cardiovascular diseases, stroke and diabetes, low cognition, visual impairment and dyspnoea (for pathologies and impairments), older age, female gender, low educational level (for risk factors), depression (for intra-individual factor) and being married, recent hospitalization and number of drugs (for extra-individual factors). Older age, male gender, tobacco consumption and living in an urban area were associated with mortality. Conclusions: These findings confirm the independent contribution of each group of variables in the disablement process and stress their different impact on progression of disability or on recovery from different grades of disability.

The changing prevalence and incidence of dementia over time — current evidence

Dementia is an increasing focus for policymakers, civil organizations and multidisciplinary researchers. The most recent descriptive epidemiological research into dementia is enabling investigation into how the prevalence and incidence are changing over time. To establish clear trends, such comparisons need to be founded on population-based studies that use similar diagnostic and research methods consistently over time. This narrative Review synthesizes the findings from 14 studies that investigated trends in dementia prevalence (nine studies) and incidence (five studies) from Sweden, Spain, the UK, the Netherlands, France, the USA, Japan and Nigeria. Besides the Japanese study, these studies indicate stable or declining prevalence and incidence of dementia, and some provide evidence of sex-specific changes. No single risk or protective factor has been identified that fully explains the observed trends, but major societal changes and improvements in living conditions, education and healthcare might have favourably influenced physical, mental and cognitive health throughout an individuals life course, and could be responsible for a reduced risk of dementia in later life. Analytical epidemiological approaches combined with translational neuroscientific research could provide a unique opportunity to explore the neuropathology that underlies changing occurrence of dementia in the general population.

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.