![]() In this proof-of-concept trial, we investigated effects of multi-domain evidence-based individually-tailored interventions on cognition, AD/cardiovascular risk scores, and AD-risk biomarkers in real-world clinical practice. 21, 22 APC’s mission is to mitigate late-life AD dementia risk by applying individualized clinical management strategies toward primary, secondary, and tertiary AD prevention while simultaneously studying its comparative effectiveness ( Figure S1). In 2013, an Alzheimer’s Prevention Clinic (APC) was established in New York, with research collaboration in Puerto Rico. 20, 21 Patients are followed longitudinally to evaluate the effectiveness of, and further refine, personally-tailored interventions. 17, 18 A term that has been used to adapt this approach, using currently available clinical assessments in everyday practice, 19 is clinical precision medicine, where medical history (e.g., lifestyle patterns, life-course events), physical/neurological examination, anthropometrics, commercially-available blood biomarkers (including genetics), and cognitive assessments inform a multi-modal management plan. ![]() 16 An overall structure of how precision medicine may be achieved in the future will be through convergence of technological advances (e.g., big data, genomic sequencing, “-omics” technologies, systems biology, integrated disease modeling) as it is hypothesized that deconstructing the disease into multiple subsets that exist within a heterogeneous population, and tailoring therapies accordingly, may be preferentially effective based on individual biological make-up (protein-protein interactions, epigenetic modifications, metabolic pathways). 12, 15 The National Institutes of Health defines precision medicine as “an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle for each person”. 14Ĭonsidering the heterogeneity of AD pathology, the application of precision medicine allows for interventions that can be targeted for individual patients. 12, 13 However, encouraging data from RCTs require translation to clinical practice, including verification of how patient compliance (or “dose response”) affects outcomes. ![]() 10, 11 Other RCTs applying lifestyle modifications have demonstrated similar effects in mild cognitive impairment (MCI) participants and adults at-risk for cognitive decline. 8, 9 The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) study was the first large long-term randomized controlled trial (RCT) showing multi-domain interventions (nutrition/physical activity/cognitive training) can maintain cognitive function and reduce the risk of cognitive impairment among at-risk older adults from the general population. 7, 8 These targetable risk factors may influence AD pathological pathways (e.g., glucose hypometabolism, inflammation, oxidative stress, amyloid burden, trophic factors). Population-attributable risk models estimate that risk factor modification (e.g., hypertension, insulin resistance, physical inactivity, hearing loss, depression) may prevent up to one-third of AD cases. 6 It is therefore important to evaluate the effectiveness of AD interventions across the disease spectrum, especially in at-risk individuals before clinically-evident decline. Further, AD drug trials may have been more successful if initiated earlier in the disease course. Given the paucity of effective AD treatments, prevention or delay of dementia is essential. ![]() ![]() 1– 4 Considering over 46 million people in the United States alone have preclinical AD, this pre-dementia period offers a unique opportunity for early intervention to address modifiable risk. Late-life Alzheimer’s disease (AD) develops over an extended preclinical period. ![]()
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