BACKGROUND Sequence variants, including the ε4 allele of apolipoprotein E, have been associated with the risk of the common late-onset form of Alzheimer’s disease. Few rare variants affecting the risk of late-onset Alzheimer’s disease have been found. METHODS We obtained the genome sequences of 2261 Icelanders and identified sequence variants that were likely to affect protein function. We imputed these variants into the genomes of patients with Alzheimer’s disease and control participants and then tested for an association with Alzheimer’s disease. We performed replication tests using case–control series from the United States, Norway, the Netherlands, and Germany. We also tested for a genetic association with cognitive function in a population of unaffected elderly persons. RESULTS A rare missense mutation (rs75932628-T) in the gene encoding the triggering receptor expressed on myeloid cells 2 (TREM2), which was predicted to result in an R47H substitution, was found to confer a significant risk of Alzheimer’s disease in Iceland (odds ratio, 2.92; 95% confidence interval [CI], 2.09 to 4.09; P = 3.42×10−10). The mutation had a frequency of 0.46% in controls 85 years of age or older. We observed the association in additional sample sets (odds ratio, 2.90; 95% CI, 2.16 to 3.91; P = 2.1×10−12 in combined discovery and replication samples). We also found that carriers of rs75932628-T between the ages of 80 and 100 years without Alzheimer’s disease had poorer cognitive function than noncarriers (P = 0.003). CONCLUSIONS Our findings strongly implicate variant TREM2 in the pathogenesis of Alzheimer’s disease. Given the reported antiinflammatory role of TREM2 in the brain, the R47H substitution may lead to an increased predisposition to Alzheimer’s disease through impaired containment of inflammatory processes. (Funded by the National Institute on Aging and others.)

As the first 1-year, multinational, double-blinded, placebo-controlled study of a cholinesterase inhibitor in AD, these data support donepezil as a well tolerated and effective long-term treatment for patients with AD, with benefits over placebo on global assessment, cognition, and ADL.

Psychiatric and behavioural symptoms are frequent in nursing homes and the rate increases with the progression of the dementia. Systematic programmes are needed for disseminating skills and providing guidance regarding the evaluation and treatment of these symptoms in nursing homes.

Findings provide good support for several somatic and lifestyle factors and will be used to inform the design of a new multicenter trial into dementia prevention.

To obtain age- and gender-specific estimates of the prevalence of dementia in Europe and to study differences in prevalence across countries, we pooled and re-analysed original data of prevalence studies of dementia carried out in some European countries between 1980 and 1990. The study followed these steps: census of existing datasets, collection of data in a standardized format, selection of datasets suitable for comparison, comparison of age and gender patterns. From the 23 datasets of European surveys considered, 12 were selected for comparison. Only population-based studies in which dementia was defined by DSM-III or equivalent criteria and in which all subjects were examined personally were included. Studies in which institutionalized subjects were not investigated were excluded. Age- and gender-specific prevalences were compared within and across studies and overall prevalences were computed. Although prevalence estimates differed across studies, the general age- and gender-distribution was similar for all studies. The overall European prevalences for the five-year age groups from 60 to 94 years, were 1.0, 1.4, 4.1, 5.7, 13.0, 21.6 and 32.2%, respectively. In subjects under 75 years the prevalence of dementia was slightly higher in men than in women; in those aged 75 years or over the prevalence was higher in women. The prevalence figures nearly doubled with every five years of increase in age.

Background: Depression is a prevalent and disabling condition in older persons (≥60 years) that increases the risk of mortality and negatively influences quality of life (QOL). The relationship between depression, or depressive symptoms, and QOL has been increasingly addressed by research in recent years, but a review that can contribute to a better understanding of this relationship in older persons is lacking. Against this background, we undertook a literature review to assess the relationship between depression and QOL in older persons. Summary: Extensive electronic database searches revealed 953 studies. Of these, 74 studies fulfilled our criteria for inclusion, of which 52 were cross-sectional studies and 22 were longitudinal studies. Thirty-five studies were conducted in a clinical setting, while 39 were community-based epidemiological studies. A clear definition of the QOL concept was described in 25 studies, and 24 different assessment instruments were employed to assess QOL. Depressed older persons had poorer global and generic health-related QOL than nondepressed individuals. An increase in depression severity was associated with a poorer global and generic health-related QOL. The associations appeared to be stable over time and independent of how QOL was assessed. Key Messages: This review found a significant association between severity of depression and poorer QOL in older persons, and the association was found to be stable over time, regardless which assessment instruments for QOL were applied. The lack of a definition of the multidimensional and multilevel concept QOL was common, and the large variety of QOL instruments in various studies make a direct comparison between the studies difficult.

BackgroundMany countries have passed laws giving patients the right to participate in decisions about health care. People with dementia cannot be assumed to be incapable of making decisions on their diagnosis alone as they may have retained cognitive abilities.The purpose of this study was to gain a better understanding of how persons with dementia participated in making decisions about health care and how their family carers and professional caregivers influenced decision making.MethodsThis Norwegian study had a qualitative multi-case design. The triad in each of the ten cases consisted of the person with dementia, the family carer and the professional caregiver, in all 30 participants. Inclusion criteria for the persons with dementia were: (1) 67 years or older (2) diagnosed with dementia (3) Clinical Dementia Rating score 2, moderate dementia; (3) able to communicate verbally. The family carers and professional caregivers were then asked to participate.A semi-structured interview guide was used in interviews with family carers and professional caregivers. Field notes were written after participant observation of interactions between persons with dementia and professional caregivers during morning care or activities at a day centre. How the professional caregivers facilitated decision making was the focus of the observations that varied in length from 30 to 90 minutes. The data were analyzed using framework analysis combined with a hermeneutical interpretive approach.ResultsProfessional caregivers based their assessment of mental competence on experience and not on standardized tests. Persons with dementia demonstrated variability in how they participated in decision making. Pseudo-autonomous decision making and delegating decision making were new categories that emerged. Autonomous decision making did occur but shared decision making was the most typical pattern. Reduced mental capacity, lack of available choices or not being given the opportunity to participate led to non-involvement. Not all decisions were based on logic; personal values and relationships were also considered.ConclusionsPersons with moderate dementia demonstrated variability in how they participated in decision making. Optimal involvement was facilitated by positioning them as capable of influencing decisions, assessing decision-specific competence, clarifying values and understanding the significance of relationships and context.

BackgroundDelirium is a common complication in patients with hip fractures and is associated with an increased risk of subsequent dementia. The aim of this trial was to evaluate the effect of a pre- and postoperative orthogeriatric service on the prevention of delirium and longer-term cognitive decline.MethodsThis was a single-center, prospective, randomized controlled trial in which patients with hip fracture were randomized to treatment in an acute geriatric ward or standard orthopedic ward. Inclusion and randomization took place in the Emergency Department at Oslo University hospital. The key intervention in the acute geriatric ward was Comprehensive Geriatric Assessment including daily interdisciplinary meetings. Primary outcome was cognitive function four months after surgery measured using a composite outcome incorporating the Clinical Dementia Rating Scale (CDR) and the 10 words learning and recalls tasks from the Consortium to Establish a Registry for Alzheimer’s Disease battery (CERAD). Secondary outcomes were pre- and postoperative delirium, delirium severity and duration, mortality and mobility (measured by the Short Physical Performance Battery (SPPB)). Patients were assessed four and twelve months after surgery by evaluators blind to allocation.ResultsA total of 329 patients were included. There was no significant difference in cognitive function four months after surgery between patients treated in the acute geriatric and the orthopedic wards (mean 54.7 versus 52.9, 95% confidence interval for the difference -5.9 to 9.5; P = 0.65). There was also no significant difference in delirium rates (49% versus 53%, P = 0.51) or four month mortality (17% versus 15%, P = 0.50) between the intervention and the control group. In a pre-planned sub-group analysis, participants living in their own home at baseline who were randomized to orthogeriatric care had better mobility four months after surgery compared with patients randomized to the orthopedic ward, measured with SPPB (median 6 versus 4, 95% confidence interval for the median difference 0 to 2; P = 0.04).ConclusionsPre- and postoperative orthogeriatric care given in an acute geriatric ward was not effective in reducing delirium or long-term cognitive impairment in patients with hip fracture. The intervention had, however, a positive effect on mobility in patients not admitted from nursing homes.Trial registrationClinicalTrials.gov NCT01009268 Registered November 5, 2009