In the Guest Editorial by Frisoni et al. an element in Table 1 (in the right-hand section “Preclinical AD: theoretical stages”) contained a misprint. Stage 1 – neurodegeneration should have been indicated by a minus sign not a plus sign.

In clinical medicine, diagnostic criteria are not only useful everyday tools for the practicing physician, but also represent a conceptual concentrate of the understanding of the etiology and pathophysiology of diseases at a given point in time. Although different sets of diagnostic criteria for Alzheimer's disease (AD) have been developed, the most widely used and best validated by clinico-pathological study to date are the NINCDS-ADRDA (National Institute of Neurological and Communicative Disorders and Stroke – Alzheimer's Disease and Related Disorders Association) criteria which were published in 1984 (McKhann et al., 1984). These criteria are largely based on the exclusion of other conditions that may cause dementia and can be succinctly but fairly summarized as defining AD as an “acquired progressive cognitive, behavioral, and functional impairment with no other obvious cause”. Clearly, the NINCDS-ADRDA criteria were etiology- and pathophysiology-agnostic in that they failed to point at any specific etiology, not even a degenerative one. They were also developed before other important causes of dementia, such as dementia with Lewy bodies, fronto-temporal dementia and subcortical vascular dementia had been fully described and characterized. The recent publication of a substantially revised version of these criteria (Sperling et al. 2011; Albert et al., 2011; McKhann et al., 2011), heralded by a largely European initiative four years ago (Dubois et al., 2007) has been greeted with great interest by the field. The newly proposed criteria reflect the substantial insights on disease pathophysiology gained over the last decades, especially regarding the molecular pathology of AD and the time course of such pathology in relation to clinical symptoms and disease.

We used data from two population-based longitudinal studies to estimate time of onset and rate of accelerated decline across cognitive domains before dementia diagnosis. The H70 includes an age-homogeneous sample (127 cases and 255 non-cases) initially assessed at age 70 with 12 follow-ups over 30 years. The Kungsholmen Project (KP) includes an age-heterogeneous sample (279 cases and 562 non-cases), with an average age of 82 years at initial assessment, and 4 follow-ups spanning 13 years. We fit mixed linear models to the data and determined placement of change points by a profile likelihood method. Results demonstrated onset of accelerated decline for fluid (speed, memory) versus crystallized (verbal, clock reading) abilities occurring approximately 10 and 5 years before diagnosis, respectively. Although decline before change points was greater for fluid abilities, acceleration was more pronounced for crystallized abilities after the change points. This suggests that onset and rate of acceleration vary systematically along the fluid-crystallized ability continuum. There is early onset in fluid abilities, but these changes are difficult to detect due to substantial age-related decline. Onset occurred later and acceleration was greater in crystallized abilities, suggesting that those markers may provide more valid identification of cases in later stages of the prodromal phase. (JINS, 2011, 17, 000–000)

Background: Cognition, abilities in activities of daily living (ADL), and behavioral disturbances in patients with Alzheimer's disease (AD) all influence the number of hours informal caregivers spend caring for their patients, and the burden caregivers experience. However, the direct effect and relative importance of each disease severity measure remains unclear.

Methods: Cross-sectional interviews were conducted with 1,222 AD patients and primary caregivers in Spain, Sweden, the U.K. and the U.S.A. Assessments included informal care hours, caregiver burden (Zarit Burden Inventory; ZBI), cognition (Mini-mental State Examination; MMSE), ADL-abilities (Disability Assessment for Dementia scale; DAD), and behavioral symptoms (Neuropsychiatric Inventory Questionnaire; NPI-severity).

Results: Multivariate analyses of 866 community-dwelling patients revealed that ADL-ability was the strongest predictor of informal care hours (36% decrease in informal care hours per standard deviation (SD) increase in DAD scores). Severity of behavioral disturbances was the strongest predictor of caregiver burden (0.35 SD increase in ZBI score per SD increase in NPI-Q severity score). In addition, the effect of ADL-abilities was, although attenuated, not negligible (0.28 SD increase in ZBI score per SD increase in DAD score). Decreasing cognition (MMSE) was associated with more informal care hours and increased caregiver burden in univariate, but not in adjusted analyses.

Conclusions: For patients residing in community dwellings, the direct influence of patients’ cognition on caregiver burden is limited and rather mediated by other disease indicators. Instead, the patients’ ADL-abilities are the main predictor of informal care hours, and both ADL-abilities and behavioral disturbances are important predictors of perceived caregiver burden, where the latter has the strongest effect. These results were consistent across Sweden, U.K. and the U.S.A.

The objective of this study is to describe the pattern of participation in leisure activities in an older population in relation to contextual factors as well as to mental and physical health. A cohort of 1,623 participants aged 75 or older living in Stockholm, Sweden was asked to list all the leisure activities they were engaged in. These were successively organised into 31 major categories and further grouped into mental, social, physical, productive and recreational types. The pattern of participation was examined in relation to age, gender, contextual factors (education, social network) and health status (depressive symptoms, cognitive impairment, dementia, somatic diseases and physical limitation). In spite of their advanced age, the majority of the population was active, as 70 per cent had participated in at least one activity. Reading (19%) was the most prevalent individual activity, and mental activities (43%) the most prevalent activity type. Older age, female gender, low education status, having a poor or limited social network, mental disorders, and physical limitation, were all factors correlated with a decreased engagement in ‘at least one activity’. Contextual factors and health-related factors were related to the five activity types in different ways. The pattern of participation in leisure activities is associated with multiple factors and their recognition is essential to the facilitation of an active lifestyle in the older population.

Objective: Clinical syndromes such as amnestic mild cognitive impairment (MCI) are highly predictive of future development of Alzheimer's disease (AD), but it is not known how many of the individuals that develop the disease can be identified with these syndromes. This study aims to determine how many individuals with AD show detectable symptoms or clinical signs of cognitive deficits three years before diagnosis.

Methods: 152 incident AD cases were identified in a dementia-free cohort of 1417 persons aged 75–95, after three-year follow-up from a prospective population-based study, the Kungsholmen Project. Symptoms of cognitive impairment including the subjective report of memory problems, and cognitive deficits were objectively measured with an extensive neuropsychological test battery at baseline. Incident AD was clinically diagnosed according to DSM-IIIR criteria at three-year follow-up.

Results: Only half of future AD cases reported subjective memory problems three years before diagnosis. More than one-third of incident AD cases did not exhibit detectable deficits in any of the investigated specific cognitive domains. Only 38.3% had both subjective complaints and domain-specific cognitive deficits.

Conclusions: Symptoms and signs currently used to define MCI are not always present in persons who develop AD. Increasing the number of potentially identifiable and treatable preclinical AD cases is unfeasible unless more sensitive subjective and objective markers are identified. Furthermore, as only half of future AD cases report subjective memory problems three years before diagnosis, the number of persons coming to the attention of medical care is limited.

Acetylcholinesterase inhibitors have demonstrated safety and efficacy in patients with mild to moderate Alzheimer's disease (AD). Although studies of biomarkers in AD suggest a neurobiological rationale for continuing cholinomimetic therapy in patients with severe AD, there have been few studies on the effects of these drugs in such patients. While the interpretation of earlier studies on therapy for severe AD has been complicated by the inclusion of patients with moderate AD, a recent study in Swedish nursing home residents demonstrates the clinical utility of donepezil in a population of exclusively severe patients – i.e. those with Mini-Mental State Examination scores of 1 to 10 inclusive. Significant differences favoring donepezil treatment were observed at the end of this six-month, double-blind placebo-controlled study on the two primary outcome measures: the Severe Impairment Battery (SIB) and Modified Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory for Severe AD (ADCS-ADL-severe). Donepezil-treated patients showed a mean improvement on the SIB after six months compared with baseline, and less decline on the ADCS-ADL-severe than would be expected for untreated patients. These results extend and confirm earlier data suggesting that donepezil is effective in patients with moderate and severe AD.

Current knowledge with respect to the diagnosis of Alzheimer's disease (AD) is reviewed. There is agreement that AD is a characteristic clinicopathologic entity that is amenable to diagnosis. The diagnosis of AD should no longer be considered one of exclusion. Rather, the diagnostic process is one of recognition of the characteristic features of AD and of conditions that can have an impact on presentation or mimic aspects of the clinicopathologic picture. The present availability of improved prognosis, management, and treatment strategies makes the proper, and state-of-the-art, diagnosis of AD a clinical imperative in all medical settings. Concurrently, information regarding the relevance and applicability of current diagnostic procedures in diverse cultural settings must continue to accrue.

Within our workshop we discussed neuropathological assessments in different cultures and countries, evaluation of dementia type, and availability of autopsy. We agreed that evaluation of dementia cases should not be limited to the use of diagnostic criteria; but neuropathologic assessment should be utilized where appropriate. We agreed that it is vital to communicate this concept to general practitioners (GPs) and physicians working in nursing homes, where there is often a high proportion of dementia patients. When neuropathologic assessments are conducted correctly, they provide both quantitative and qualitative information about cell and tissue damage. The assessment should preferably be performed by a neuropathologist in order that a diagnosis plus an estimation of disease severity and extent can be made.

Knowledge about the health economic implications of vascular dementia (VaD) is insufficient. The impact of cardiovascular comorbidities must also be taken into consideration when resource utilization and costs in patients with VaD are analyzed. It is also of great importance that the analysis be done from a societal perspective. In the rural Nordanstig cohort of the Kungsholmen project in Sweden, the major cost drivers in the RUD (Resource Utilization in Dementia) instrument were used. The cost from a societal perspective was 23% higher for patients with VaD compared with patients with Alzheimer's disease (p = .02).

The proportion of institutionalized and noninstitutionalized demented people differs among countries. In the Kungsholmen study in Sweden, in the total population 75 years and older, around 50% of the demented people lived in their own homes and 50% lived in various types of institutions. In the future, it may not be possible, for ideological and financial reasons, to build new institutions to take care of the increasing number of dependent and ill elderly. Home care with support for relatives, day care, and collective living are better alternatives for some demented people.

This study describes how demented immigrants' communicative performance together with caregivers who speak/do not speak these people's native language relates to the demented persons' cognitive, linguistic, and neuropsychological abilities. The study was carried out among demented persons who were born in Finland and had immigrated to Sweden. Their life history, linguistic history and linguistic behavior, and communication in standardized situations were assessed. Neuropsychological and medical examinations were performed for diagnostic reasons. The results show that many of these Finnish immigrants had difficulties communicating with their Swedish-speaking caregivers, while their communication with a Finnish-speaking caregiver was adequate. The frequent misunderstanding of a person's message often leads to a one-way communication, in which the caregiver commands and interrupts the demented person. The demented Finnish immigrants functioned on a level of manifest competence that seemed far below their level of latent competence. It seems reasonable that the presence of Finnish-speaking caregivers is an environmental change that would markedly enhance the demented Finnish immigrants' performance and quality of life and also reduce the costs for their care.