Alzheimer's disease with frailty: Prevalence, screening, assessment, intervention strategies and challenges

Alzheimer's disease (AD) is a neurodegenerative disorder that affects millions worldwide and is expected to surge in prevalence due to aging populations. Frailty, characterized by muscle function decline, becomes more prevalent with age, imposing substantial burdens on patients and caregivers. This paper aimed to comprehensively review the current literature on AD coupled with frailty, encompassing prevalence, screening, assessment, and treatment while delving into the field's challenges and future trajectories. Frailty and AD coexist in more than 30% of cases, with hazard ratios above 120% indicating a mutually detrimental association.Various screening tools have emerged for both frailty and AD, including the Fried Frailty Phenotype (FP), FRAIL scale, Edmonton Frailty Scale (EFS), Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Clock Drawing Test (CDT), and General Practitioner Assessment of Cognition (GPCOG). However, none has solidified its role as the definitive gold standard. The convergence of electronic health records and brain aging biomarkers heralds a new era in AD with frailty screening and assessment. In terms of intervention, non-pharmacological strategies spanning nutrition, horticulture, exercise, and social interaction, along with pharmacological approaches involving acetylcholinesterase inhibitors (AChEIs), N-methyl-D-aspartate (NMDA) receptor antagonists, and anti-amyloid beta-protein medications, constituted cornerstones for treating AD coupled with frailty. Technological interventions like repetitive transcranial magnetic stimulation (rTMS) also entered the fold. Notably, multi-domain non-pharmacological interventions wield considerable potential in enhancing cognition and mitigating disability. However, the long-term efficacy and safety of pharmacological interventions necessitate further validation. Diagnosing and managing AD with frailty present several daunting challenges, encompassing low rates of early co-diagnosis, limited clinical trial evidence, and scarce integrated, pioneering service delivery models. These challenges demand heightened attention through robust research and pragmatic implementation.