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...

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The highly complex structure of the human brain is strongly shaped by genetic influences1. Subcortical brain regions form circuits with cortical areas to coordinate movement2, learning, memory3 and motivation4, and altered circuits can lead to abnormal behaviour and disease2. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume5 and intracranial volume6. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 × 10−33; 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability inhuman brain development, and may help to determine mechanisms of neuropsychiatric dysfunction.