This approach, describing the 14 years preceding dementia, provides a clear illustration of the particularly long and progressive prodromal phase of AD, and shows the successive emergence of cognitive deficits, depressive symptoms, and functional impairment during this phase.

Dementia, a syndrome of cognitive decline severe enough to interfere with daily functioning and independent living, has been the subject of increasing focus for policymakers, civil organisations and multidisciplinary researchers. A substantial body of the most recent descriptive epidemiological research on dementia is allowing investigation of how prevalence and incidence might be changing across time. To establish clear trends, such comparisons need to be based on population-based studies using similar diagnostic and research methods over time. This review synthesises findings from nine prevalence trend studies and five incidence trend studies from western European countries (Sweden, Spain, UK, the Netherlands and France), the US, Japan and Nigeria. These population-based studies, apart from the Japanese study, have reported stable or declining prevalence and incidence and evidence of both inconsistent and similar changes in men and women within and across countries. No single risk or protective factor has been identified to fully explain these trends, but major societal changes in western societies and improvement in factors potentially associated with risk and protecting such as living conditions, higher education attainment and wider availability of healthcare might have favourably influenced multiple factors related to physical, mental and cognitive health across the lifecourse and could be responsible for this reduced risk of dementia in later life. Analytical epidemiologic approaches combined with translational neuroscientific research may provide a unique opportunity to explore underlying mechanisms of neuropathology and dementia in the general population. The findings from these studies provide robust evidence for developing fruitful avenues for prevention, diagnosis and treatment.

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.

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BackgroundHerpes 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.MethodsCox 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.ResultsDuring 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.ConclusionReactivation of HSV seropositivity is highly correlated with incident AD. HSV chronic infection may therefore be contributive to the progressive brain damage characteristic of AD.

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.

The identification of biological and pathophysiological processes implicated in different forms of dementia is itself dependent on reliable descriptions of cognitive performance and capacities. However, traditional instruments are often unable to detect subtle declines in cognitive functions due to natural variation at the time of testing. Mobile technologies permit the repeated assessment of cognitive functions and may thereby provide more reliable descriptions of early cognitive difficulties that are inaccessible to clinic or hospital-based instruments. This assessment strategy is also able to characterize in real-time the dynamic associations between cognitive performance and specific daily life behaviors or activities. In a cohort of elderly rural residents, 60 individuals were administered neuropsychological and neuroimaging exams as well as a one-week period of electronic ambulatory monitoring of behavior, semantic memory performance, and daily life experiences. Whereas imaging markers were unrelated to traditional neuropsychological test scores, they were significantly associated with mobile assessments of semantic memory performance. Moreover, certain daily life activities such as reading or completing crossword puzzles were associated with increases in semantic memory performance over the subsequent hours of the same day. The revolution in mobile technologies provides unprecedented opportunities to overcome the barriers of time and context that characterize traditional hospital and clinical-based assessments. The combination of both novel and traditional methods should provide the best opportunity for identifying the earliest risk factors and biomarkers for Alzheimer's disease and other forms of dementia.

Insomnia symptoms, EDS, and the use of medication independently increase the risk of subsequent depression in the elderly. In clinical practice, disturbed sleep and prolonged use of sleep medication may be early indicators or potentially reversible risk factors for depression, suggesting the need for further clinical interventional research.