Prof J Cohen-Mansfield), and Minerva Center for Interdisciplinary Study of End of Life (Prof J Cohen-Mansfield),should consider dementia in older people without known dementia who have frequent admissions or who develop delirium. Delirium is common in people with dementia and contributes to cognitive decline. In hospital, care including appropriate sensory stimulation, ensuring fluid intake, and avoiding infections might reduce delirium incidence.Acting now on dementia prevention, intervention, and care will vastly improve living and dying for individuals with dementia and their families, and thus society.

People with dementia are usually older, often have co-morbidities and may need help in coping with these illnesses. A third of older people now die with dementia and all professionals working in endof-life care need to make this a central part of their planning and communication. In this commission, we have detailed evidence-based approaches to dementia and its symptoms. Services should be available, scalable and give value. As there are limited resources, professionals and services need to use what works, not use what is ineffective, and be aware of the difference. Overall, there is good potential for prevention and, once someone develops dementia, for care to be high-quality, accessible, and give value to an under-served, growing population. Effective dementia prevention and care could transform the future for society and vastly improve living and dying for individuals with dementia and their families. Acting now on what we already know can make this difference happen. Key Messages 1 There are increasing numbers of people with dementia globally although incidence in some countries has decreased. 2 Be ambitious about prevention: We recommend energetically treating hypertension in middle aged and older people without dementia to reduce dementia incidence. Interventions for other risk factors, including more childhood education, exercise, maintaining social engagement, reducing smoking, and management of hearing loss, depression, diabetes and obesity; may have the potential of delaying or preventing a third of dementias. 3 Treat cognitive symptoms: To maximise cognition, people with Alzheimer's dementia or Dementia with Lewy Bodies should be offered Cholinesterase Inhibitors (ChEIs)at all stages, or memantine for severe dementia. ChEIs are not effective in Mild Cognitive Impairment. 4 Individualise dementia care: Good dementia care spans medical, social and supportive care, should be tailored to unique individual and cultural needs, preferences, priorities, and should incorporate support for the family carers 5 Care for family carers. Family carers are at high risk of depression. Effective interventions reduce the risk and treat the symptoms, include START (Strategies for Relatives) or REACH (Resources for Enhancing Alzheimer's Caregiver Health intervention) and should be made available. 6 Plan for the future. People with dementia and their families value discussions about the future and decisions about possible attorneys to make decisions. Clinicians should consider capacity to make different types of decisions at diagnosis. 7 Protect people with dementia. People with dementia and society require protection from possible risks of the condition, including self-neglect, vulnerability including to exploitation, managing money, driving or using weapons. Risk assessment and management at all stages of the disease is essential but it should be balanced against the persons' right to autonomy. 8 Manage neuropsychiatric symptoms. Management of the neuropsychiatric symptoms of dementia including agitation, low mood or psyc...

Alzheimer's disease (AD) is highly heritable and recent studies have identified over 20 diseaseassociated genomic loci. Yet these only explain a small proportion of the genetic variance, indicating that undiscovered loci remain. Here, we performed the largest genome-wide association study of clinically diagnosed AD and AD-by-proxy (71,880 cases, 383,378 controls). AD-by-proxy, based on parental diagnoses, showed strong genetic correlation with AD (rg=0.81). Meta-analysis identified 29 risk loci, implicating 215 potential causative genes. Associated genes are strongly expressed in immune-related tissues and cell types (spleen, liver and microglia). Gene-set analyses indicate biological mechanisms involved in lipid-related processes and degradation of amyloid precursor proteins. We show strong genetic correlations with multiple health-related outcomes, and Mendelian randomisation results suggest a protective effect of cognitive ability on AD risk. These results are a step forward in identifying the genetic factors that contribute to AD risk and add novel insights into the neurobiology of AD.

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.

Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele.

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.

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Mutations leading to premature termination codons in ATP-Binding Cassette Subfamily A Member 7 (ABCA7) are high pen-etrant risk factors of Alzheimer's disease (AD). The influence of other genetic variants in ABCA7 and downstream functional mechanisms, however, is poorly understood. To address this knowledge gap, we investigated tandem repetitive regions in ABCA7 in a Belgian cohort of 1529 AD patients and control individuals and identified an intronic variable number tandem repeat (VNTR). We observed strong association between VNTR length and a genome-wide associated signal for AD in the ABCA7 locus. Expanded VNTR alleles were highly enriched in AD patients [odds ratio = 4.5 (1.3-24.2)], and VNTR length inversely correlated with amyloid β 1-42 in cerebrospinal fluid and ABCA7 expression. In addition, we identified three novel ABCA7 alternative splicing events. One isoform in particular-which is formed through exon 19 skipping-lacks the first nucleotide binding domain of ABCA7 and is abundant in brain tissue. We observed a tight correlation between exon 19 skipping and VNTR length. Our findings underline the importance of studying repetitive DNA in complex disorders and expand the contribution of genetic and transcript variation in ABCA7 to AD.