Modifiable risk factors for dementia and dementia risk profiling. A user manual for Brain Health Services—part 2 of 6

Abstract

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.

Altered Balance of Reelin Proteolytic Fragments in the Cerebrospinal Fluid of Alzheimer’s Disease Patients

“…The ever-growing prevalence of Alzheimer’s disease (AD) is associated with the sporadic presentation of the disease [ 1 , 2 ]. Sporadic AD is a multifactorial disease with environmental contributing causes (mainly age); however, genetic risk factors are also important [ 3 , 4 , 5 ]. Amongst the numerous genes implicated in AD pathogenesis, the most prominent genetic risk factor is the apolipoprotein E (apoE) encoding gene, APOE .…”

Prodromal Parkinson's disease: hype or hope for disease-modification trials?

“…At the other end of the spectrum, successful disease-modification in prodromal PD might eventually require drug combinations addressing multiple targets, not unlike what is common practice in primary prevention of cardiovascular disease. The latter example also highlights the potential role of life-style modifications in reducing disease risk, an area that has been explored to some extent in neurodegenerative diseases like PD or Alzheimer’s disease, where physical and mental activity, dietary, drinking and smoking habits, as well as control of vascular co-morbidities have been shown to modify disease risk [ 100 – 102 ]. While there are significant challenges regarding controlled prospective studies of the effects of such factors on the evolution of disease in prodromal subjects, they would nonetheless be essential for individual patients [ 103 ] and for evidence-based PD risk-management at the public health level.…”

Dementia Risk Scores and Their Role in the Implementation of Risk Reduction Guidelines

“…In this section, three examples of risk scores based on modifiable risk factors for dementia or AD which have been implemented into clinical trials or practice ( 52 ) are presented in the order in which they were developed. Their developments have been described in detail previously ( 8 , 53 , 54 ), and their algorithms are summarized in Table 1 .…”