Cognitive Frailty and Aging: Clinical Characteristics, Pathophysiological Mechanisms, and Potential Prevention Strategies

Frailty has been conceptualized not only as a physical disease, but also as a multidomain entity that encompasses a multimorbid status, disability, cognitive impairment, psychosocial risk factors, and even geriatric syndromes. In addition to physical ailments and depending on the diagnostic model. Standardized neuropsychological tests can identify cognitive deficiencies along with mild cognitive impairment, a pre-dementia stage characterized by memory and/or other cognitive domain impairments with relatively preserved instrumental activities of daily living. Hence, the possibility of cognitive frailty (CF), a construct that refers to physical frailty in concurrence with non-dementia cognitive decline, is proposed. The estimated prevalence of CF ranges from 10.3 to 42.8%. It is likely that the pathway to overt cognitive impairment, which does not yet involve physical function, begins with the asymptomatic early accumulation of progressive brain damage. Thus, timely detection strategies that target the initial phases of CF are warranted. The pathophysiological components of CF include dysregulation of the hypothalamic-pituitary axis stress response, imbalance in energy metabolism, impaired cardiovascular function, mitochondrial deterioration, and vascular age-related arterial stiffness. Changes that contribute to this disease can also occur at the cellular level, including overexpression of the renin-angiotensin-aldosterone system, activation of proinflammatory pathways, endothelial dysfunction, reduced nitric oxide production, and increased oxidative stress. Non-pharmacological interventions, that range from dietary and nutritional counseling to psychosocial therapy, are currently the main approaches. Both cognitive and physical training programs are considered to be the best researched and most useful multidomain interventions. Clinicians recognize CF as a valid concept that warrants prevention and treatment strategies supported by current research.