Unit of Research Methodology and Data Sciences for Population Health, National Institute of Gastroenterology "Saverio de Bellis", Research Hospital, Castellana Grotte, Bari, Italy.
"Cesare Frugoni" Internal and Geriatric Medicine and Memory Unit, University of Bari "Aldo Moro", Bari, Italy.
J Alzheimers Dis. 2023;94(3):879-898. doi: 10.3233/JAD-230312.
In older age, frailty is a detrimental transitional status of the aging process featuring an increased susceptibility to stressors defined by a clinical reduction of homoeostatic reserves. Multidimensional frailty phenotypes have been associated with all-cause dementia, mild cognitive impairment (MCI), Alzheimer's disease (AD), AD neuropathology, vascular dementia, and non-AD dementias. In the present article, we reviewed current evidence on the existing links among depressive and biopsychosocial frailty phenotypes and late-life cognitive disorders, also examining common pathways and mechanisms underlying these links. The depressive frailty phenotype suggested by the construct of late-life depression (LLD) plus physical frailty is poorly operationalized. The biopsychosocial frailty phenotype, with its coexistent biological/physical and psychosocial dimensions, defines a biological aging status and includes motivational, emotional, and socioeconomic domains. Shared biological pathways/substrates among depressive and biopsychosocial frailty phenotypes and late-life cognitive disorders are hypothesized to be inflammatory and cardiometabolic processes, together with multimorbidity, loneliness, mitochondrial dysfunction, dopaminergic neurotransmission, specific personality traits, lack of subjective/objective social support, and neuroendocrine dysregulation. The cognitive frailty phenotype, combining frailty and cognitive impairment, may be a risk factor for LLD and vice versa, and a construct of depressive frailty linking physical frailty and LLD may be a good dementia predictor. Frailty assessment may enable clinicians to better target the pharmacological and psychological treatment of LLD. Given the epidemiological links of biopsychosocial frailty with dementia and MCI, multidomain interventions might contribute to delay the onset of late-life cognitive disorders and other adverse health-related outcomes, such as institutionalization, more frequent hospitalization, disability, and mortality.
在老年时期，衰弱是衰老过程中的一种不利过渡状态，其特征是对由体内稳态储备减少定义的应激源的易感性增加。多维衰弱表型与全因痴呆、轻度认知障碍（MCI）、阿尔茨海默病（AD）、AD 神经病理学、血管性痴呆和非 AD 痴呆有关。在本文中，我们回顾了目前关于抑郁和生物心理社会衰弱表型与晚年认知障碍之间现有联系的证据，同时也检查了这些联系背后的常见途径和机制。由晚年抑郁症（LLD）加上身体衰弱构建的抑郁衰弱表型操作性较差。生物心理社会衰弱表型，其共存的生物学/身体和心理社会维度，定义了一种生物学衰老状态，并包括动机、情感和社会经济领域。假设抑郁和生物心理社会衰弱表型与晚年认知障碍之间存在共同的生物学途径/底物，包括炎症和心脏代谢过程，以及多种合并症、孤独、线粒体功能障碍、多巴胺能神经传递、特定的人格特质、缺乏主观/客观社会支持以及神经内分泌失调。将衰弱和认知障碍结合起来的认知衰弱表型可能是 LLD 的一个危险因素，反之亦然，将身体衰弱和 LLD 联系起来的抑郁衰弱构念可能是痴呆的一个很好的预测指标。衰弱评估可以使临床医生更好地针对 LLD 的药物和心理治疗。鉴于生物心理社会衰弱与痴呆和 MCI 的流行病学联系，多领域干预可能有助于延缓晚年认知障碍和其他与健康相关的不良后果（如住院、残疾和死亡）的发生。
