The Neurochemistry of Alzheimer’s Disease: One of the Most Common Causes of Reduced Capability in the Adult Population

Alzheimer’s disease (AD) is the most common form of dementia and is characterised by the triad of amyloid plaques, tau pathology and neurodegeneration. Except for a strong association with the susceptibility gene, specifically the apolipoprotein E (APOE) ε4 allele, the pathogenesis of the most common age-related sporadic form of AD is largely unknown. However, several genetic and environmental risk factors have been proposed. A potential problem is that most population-based studies on AD risk-profiling have not used biomarkers reflecting amyloid and tau pathology to classify patients and controls. Given the complex pathophysiology of late-onset AD and the difficulties in correctly diagnosing AD on purely clinical grounds, this introduces a risk of misclassification of both control subjects and clinically diagnosed AD cases. Importantly, in recent years, there has been a very successful development of blood biomarkers for AD pathophysiologies, including brain amyloidosis (amyloid β ratio), tau pathology (phosphorylated tau) and neurodegeneration (neurofilament light). Numerous studies have shown these biomarkers to correlate with amyloid and tau pathology load evaluated by PET and with MRI measures of neurodegeneration, and to predict future cognitive decline. The employment of blood biomarkers in epidemiological studies may foster an understanding of which and how specifically lifestyle risk factors are linked to AD, and repeated blood sampling in intervention trials may provide evidence as to whether controlling lifestyle factors may affect specific AD pathophysiologies.

Dementia risk communication. A user manual for Brain Health Services—part 3 of 6

Growing evidence suggests dementia incidence can be reduced through prevention programs targeting risk factors. To accelerate the implementation of such prevention programs, a new generation of brain health services (BHS) is envisioned, involving risk profiling, risk communication, risk reduction, and cognitive enhancement. The purpose of risk communication is to enable individuals at risk to make informed decisions and take action to protect themselves and is thus a crucial step in tailored prevention strategies of the dementia incidence. However, communicating about dementia risk is complex and challenging.In this paper, we provide an overview of (i) perspectives on communicating dementia risk from an ethical, clinical, and societal viewpoint; (ii) insights gained from memory clinical practice; (iii) available evidence on the impact of disclosing APOE and Alzheimer’s disease biomarker test results gathered from clinical trials and observational studies; (iv) the value of established registries in light of BHS; and (v) practical recommendations regarding effective strategies for communicating about dementia risk.In addition, we identify challenges, i.e., the current lack of evidence on what to tell on an individual level—the actual risk—and on how to optimally communicate about dementia risk, especially concerning worried yet cognitively unimpaired individuals. Ideally, dementia risk communication strategies should maximize the desired impact of risk information on individuals’ understanding of their health/disease status and risk perception and minimize potential harms. More research is thus warranted on the impact of dementia risk communication, to (1) evaluate the merits of different approaches to risk communication on outcomes in the cognitive, affective and behavioral domains, (2) develop an evidence-based, harmonized dementia risk communication protocol, and (3) develop e-tools to support and promote adherence to this protocol in BHSs.Based on the research reviewed, we recommend that dementia risk communication should be precise; include the use of absolute risks, visual displays, and time frames; based on a process of shared decision-making; and address the inherent uncertainty that comes with any probability.

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

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.

1230 Infrainguinal Bypass Informed Consent: An Audit Driven Standardisation Of Perioperative Risk Profiling

Introduction It is a fundamental good clinical practice in our medicolegal rights era to obtain standard, adequate, and transparent informed consent before any planned intervention. Currently, there are neither national approved vascular intervention-specific consents nor explicit guidelines for it. We aim to achieve a standardisation of perioperative risk profiling of infrainguinal bypass surgical consents and produce a model one. Method A retrospective analysis of 45 infrainguinal bypass consents (audit/reaudit) between (2013-2019) retrieved to evaluate quality and completeness against GMC 2008 guidance: "Consent: patients and doctors making decisions together". Data included basic consent requirements according to guidelines and specific risks of infrainguinal bypass. It was registered with the Trust Clinical Audit Department. Results (100%) of audit and reaudit consents documented the intended benefits of surgery. Inclusion into the National Vascular Registry (NVR) was achieved (0%) in audit vs (80%) in reaudit forms. Of the 19 documented postoperative complications, reaudit significant improvement observed in % of documenting 16 items with 9 complications recorded above 50%. The maximum number of audit documented risks was 15 (79%), the median 8 (42%), and the least was 3 (16%) compared to maximum 16 (84%), the median 10 (53%) and the least was 4 (21%) when reaudited, respectively. Conclusions Deficiencies in performing and adequately completing surgical consents still occur. Introducing a national pre-printed vascular intervention-specific consent is vital for accomplishing and maintaining a good clinical practice. It should include all complications with relative % risk to minimise errors, provide good quality consent, and promote clinical practice at a national level.