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Although prevention of dementia and late-life cognitive decline is a major public health priority, there are currently no generally established prevention strategies or operational models for implementing such strategies into practice. This article is a narrative review of available evidence from multidomain dementia prevention trials targeting several risk factors and disease mechanisms simultaneously, in individuals without dementia at baseline. Based on the findings, we formulate recommendations for implementing precision risk reduction strategies into new services called Brain Health Services. A literature search was conducted using medical databases (MEDLINE via PubMed and SCOPUS) to select relevant studies: non-pharmacological multidomain interventions (i.e., combining two or more intervention domains), target population including individuals without dementia, and primary outcomes including cognitive/functional performance changes and/or incident cognitive impairment or dementia. Further literature searches covered the following topics: sub-group analyses assessing potential modifiers for the intervention effect on cognition in the multidomain prevention trials, dementia risk scores used as surrogate outcomes in multidomain prevention trials, dementia risk scores in relation to brain pathology markers, and cardiovascular risk scores in relation to dementia. Multidomain intervention studies conducted so far appear to have mixed results and substantial variability in target populations, format and intensity of interventions, choice of control conditions, and outcome measures. Most trials were conducted in high-income countries. The differences in design between the larger, longer-term trials that met vs. did not meet their primary outcomes suggest that multidomain intervention effectiveness may be dependent on a precision prevention approach, i.e., successfully identifying the at-risk groups who are most likely to benefit. One such successful trial has already developed an operational model for implementing the intervention into practice. Evidence on the efficacy of risk reduction interventions is promising, but not yet conclusive. More long-term multidomain randomized controlled trials are needed to fill the current evidence gaps, especially concerning low- and middle-income countries and integration of dementia prevention with existing cerebrovascular prevention programs. A precision risk reduction approach may be most effective for dementia prevention. Such an approach could be implemented in Brain Health Services.

Dementia has a devastating impact on the quality of life of patients and families and comes with a huge cost to society. Dementia prevention is considered a public health priority by the World Health Organization. Delaying the onset of dementia by treating associated risk factors will bring huge individual and societal benefit. Empirical evidence suggests that, in higher-income countries, dementia incidence is decreasing as a result of healthier lifestyles. This observation supports the notion that preventing dementia is possible and that a certain degree of prevention is already in action. Further reduction of dementia incidence through deliberate prevention plans is needed to counteract its growing prevalence due to increasing life expectancy.An increasing number of individuals with normal cognitive performance seek help in the current memory clinics asking an evaluation of their dementia risk, preventive interventions, or interventions to ameliorate their cognitive performance. Consistent evidence suggests that some of these individuals are indeed at increased risk of dementia. This new health demand asks for a shift of target population, from patients with cognitive impairment to worried but cognitively unimpaired individuals. However, current memory clinics do not have the programs and protocols in place to deal with this new population.We envision the development of new services, henceforth called Brain Health Services, devoted to respond to demands from cognitively unimpaired individuals concerned about their risk of dementia. The missions of Brain Health Services will be (i) dementia risk profiling, (ii) dementia risk communication, (iii) dementia risk reduction, and (iv) cognitive enhancement. In this paper, we present the organizational and structural challenges associated with the set-up of Brain Health Services.

Brain Health Services are a novel approach to the personalized prevention of dementia. In this paper, we consider how such services can best reflect their social, cultural, and economic context and, in doing so, deliver fair and equitable access to risk reduction. We present specific areas of challenge associated with the social context for dementia prevention. The first concentrates on how Brain Health Services engage with the "at-risk" individual, recognizing the range of factors that shape an individual's risk of dementia and the efficacy of risk reduction measures. The second emphasizes the social context of Brain Health Services themselves and their ability to provide equitable access to risk reduction. We then elaborate proposals for meeting or mitigating these challenges. We suggest that considering these challenges will enable Brain Health Services to address two fundamental questions: the balance between an individualized "high-risk" and population focus for public health prevention and the ability of services to meet ethical standards of justice and health equity.

We envisage the development of new Brain Health Services to achieve primary and secondary dementia prevention. These services will complement existing memory clinics by targeting cognitively unimpaired individuals, where the focus is on risk profiling and personalized risk reduction interventions rather than diagnosing and treating late-stage disease. In this article, we review key potentially modifiable risk factors and genetic risk factors and discuss assessment of risk factors as well as additional fluid and imaging biomarkers that may enhance risk profiling. We then outline multidomain measures and risk profiling and provide practical guidelines for Brain Health Services, with consideration of outstanding uncertainties and challenges. Users of Brain Health Services should undergo risk profiling tailored to their age, level of risk, and availability of local resources. Initial risk assessment should incorporate a multidomain risk profiling measure. For users aged 39–64, we recommend the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) Dementia Risk Score, whereas for users aged 65 and older, we recommend the Brief Dementia Screening Indicator (BDSI) and the Australian National University Alzheimer’s Disease Risk Index (ANU-ADRI). The initial assessment should also include potentially modifiable risk factors including sociodemographic, lifestyle, and health factors. If resources allow, apolipoprotein E ɛ4 status testing and structural magnetic resonance imaging should be conducted. If this initial assessment indicates a low dementia risk, then low intensity interventions can be implemented. If the user has a high dementia risk, additional investigations should be considered if local resources allow. Common variant polygenic risk of late-onset AD can be tested in middle-aged or older adults. Rare variants should only be investigated in users with a family history of early-onset dementia in a first degree relative. Advanced imaging with 18-fluorodeoxyglucose positron emission tomography (FDG-PET) or amyloid PET may be informative in high risk users to clarify the nature and burden of their underlying pathologies. Cerebrospinal fluid biomarkers are not recommended for this setting, and blood-based biomarkers need further validation before clinical use. As new technologies become available, advances in artificial intelligence are likely to improve our ability to combine diverse data to further enhance risk profiling. Ultimately, Brain Health Services have the potential to reduce the future burden of dementia through risk profiling, risk communication, personalized risk reduction, and cognitive enhancement interventions.

Public acceptance is critical for sharing of genomic data at scale. This paper examines how acceptance of data sharing pertains to the perceived similarities and differences between DNA and other forms of personal data. It explores the perceptions of representative publics from the USA, Canada, the UK and Australia (n = 8967) towards the donation of DNA and health data. Fifty-two percent of this public held 'exceptionalist' views about genetics (i.e., believed DNA is different or 'special' compared to other types of medical information). This group was more likely to be familiar with or have had personal experience with genomics and to perceive DNA information as having personal as well as clinical and scientific value. Those with personal experience with genetics and genetic exceptionalist views were nearly six times more likely to be willing to donate their anonymous DNA and medical information for research than other respondents. Perceived harms from re-identification did not appear to dissuade publics from being willing to participate in research. The interplay between exceptionalist views about genetics and the personal, scientific and clinical value attributed to data would be a valuable focus for future research.

Understanding processes that generate and maintain large disjunctions within plant species can provide valuable insights into plant diversity and speciation. The butterfly bush Buddleja alternifolia has an unusual disjunct distribution, occurring in the Himalaya, Hengduan Mountains (HDM) and the Loess Plateau (LP) in China. We generated a high-quality, chromosome-level genome assembly of B. alternifolia, the first within the family Scrophulariaceae. Whole genome resequencing data from 48 populations plus morphological and petal color reflectance data covering its full distribution range were collected. Three distinct genetic lineages of B. alternifolia were uncovered, corresponding to Himalayan, HDM and LP material, with the last also differentiated morphologically and phenologically, indicating occurrence of allopatric speciation likely facilitated by geographic isolation and divergent adaptation to distinct ecological niches. Moreover, speciation with gene flow between populations from either side of a mountain barrier could be under way within LP. The current disjunctions within B. alternifolia might result from vicariance of a once widespread distribution, followed by several past contraction and expansion events, possibly linked to climate fluctuations promoted by the Kunlun-Yellow river tectonic movement. Several adaptive genes are likely either uniformly or diversely selected among regions, providing a footprint of local adaptations. These findings provide new insights into plant biogeography, adaptation and different processes of allopatric speciation.