Like virtually all age-related chronic diseases, late-onset Alzheimer’s disease (AD) develops over an extended preclinical period and is associated with modifiable lifestyle and environmental factors. We hypothesize that multimodal interventions that address many risk factors simultaneously and are individually tailored to patients may help reduce AD risk. We describe a novel clinical methodology used to evaluate and treat patients at two Alzheimer’s Prevention Clinics. The framework applies evidence-based principles of clinical precision medicine to tailor individualized recommendations, follow patients longitudinally to continually refine the interventions, and evaluate N-of-1 effectiveness (trial registered at ClinicalTrials.gov NCT03687710). Prior preliminary results suggest that the clinical practice of AD risk reduction is feasible, with measurable improvements in cognition and biomarkers of AD risk. We propose using these early findings as a foundation to evaluate the comparative effectiveness of personalized risk management within an international network of clinician researchers in a cohort study possibly leading to a randomized controlled trial.

Introduction The NIH Toolbox Cognition Battery (NIHTB-CB) is a computer-based protocol not yet validated for clinical assessment. Methods We administered the NIHTB-CB and traditional neuropsychological tests to 247 Memory Disorders and Alzheimer's Prevention Clinic patients with subjective cognitive decline, mild cognitive impairment, mild dementia due to Alzheimer's disease, and normal cognition. Principal component analysis, partial correlations, and univariate general linear model tests were performed to assess construct validity. Discriminant function analyses compared classification accuracy. Results Principal component analysis identified three conceptually coherent factors: memory (MEM NIH ), executive function (EF NIH ), and crystallized intelligence (CI NIH ). These factors were strongly associated with corresponding traditional tests and differed across diagnostic groups as expected. Both NIHTB and traditional batteries yielded strong overall discriminative ability (>80%). Discussion The NIHTB-CB is a valid method to assess neurocognitive domains pertinent to aging and dementia and has utility for applications in a memory clinic setting.

Summary INTRODUCTION: Multi-domain intervention for Alzheimer’s disease (AD) risk reduction is an emerging therapeutic paradigm. METHODS: Patients were prescribed individually-tailored interventions (education/pharmacologic/non-pharmacologic) and rated on compliance. Normal cognition/subjective cognitive decline/preclinical-AD were classified as Prevention. Mild cognitive impairment due to AD/mild-AD were classified as Early Treatment. Change from baseline to 18-months on the modified-Alzheimer’s Prevention Cognitive Composite (primary outcome) was compared against matched historical control cohorts. Cognitive aging composite (CogAging), AD/cardiovascular risk-scales, and serum biomarkers were secondary outcomes. RESULTS: 174 were assigned interventions (age 25–86). Higher-compliance Prevention improved more than both historical cohorts (P=.0012,P<.0001). Lower-compliance Prevention also improved more than both historical cohorts (P=.0088,P<.0055). Higher-compliance Early Treatment improved more than lower-compliance (P=.0007). Higher-compliance Early Treatment improved more than historical cohorts (P<.0001,P=.0428). Lower-compliance Early Treatment did not differ (P=.9820,P=.1115). Similar effects occurred for CogAging. AD/cardiovascular risk-scales and serum biomarkers improved. DISCUSSION: Individualized multi-domain interventions may improve cognition and reduce AD/cardiovascular risk scores in patients at-risk for AD-dementia.

Alzheimer’s disease (AD) is a major source of morbidity and mortality, with the disease burden expected to rise as the population ages. No disease-modifying agent is currently available, but recent research suggests that nutritional and lifestyle modifications can delay or prevent the onset of AD. However, preventive nutritional interventions are not universally applicable and depend on the clinical profile of the individual patient. This article reviews existing nutritional modalities for AD prevention that act through improvement of insulin resistance, correction of dyslipidemia, and reduction of oxidative stress, and discusses how they may be modified on the basis of individual biomarkers, genetics, and behavior. In addition, we report preliminary results of clinical application of these personalized interventions at the first AD prevention clinic in the United States. The use of these personalized interventions represents an important application of precision medicine techniques for the prevention of AD that can be adopted by clinicians across disciplines.

Objective:Relative to dementia, little is known about informant bias in mild cognitive impairment (MCI). We investigated the influence of informant demographic and relational characteristics on reports of everyday functioning using the Functional Activities Questionnaire (FAQ).Method:Four thousand two hundred eighty-four MCI participants and their informants from the National Alzheimer’s Coordinating Center Uniform Data Set were included. Informants were stratified according to cohabitation, relationship, visit frequency, race/ethnicity, education, and sex. Informant-rated Mean FAQ score was compared across these groups using univariate general linear model analyses and post hoc tests. Interactions were tested between informant variables. The predictive contribution of informant variables to FAQ score was explored using hierarchical linear regression. Analyses covaried for participant cognition using a cognitive composite score, and for participant age, sex, and depression.Results:After controlling for participant cognition, depression, age, and sex, informant-rated FAQ scores varied significantly across all informant variables (p’s < .005, ηp2’s ≤ .033) except sex and visit frequency. FAQ scores were higher (more impaired) among informants who cohabitate with the participant, among paid caregivers, spouses, and adult children, and among informants with higher levels of education. Scores were lowest (less impaired) among Black/African American informants as compared to all other racial/ethnic groups.Conclusions:Demographic and relational characteristics of informants influence the perception and reporting of instrumental activities of daily living in adults with MCI. As everyday functioning is crucial for differential diagnosis and treatment outcome measurement, it is important to be aware of sources of informant report discrepancies.