Depressive and Biopsychosocial Frailty Phenotypes: Impact on Late-life Cognitive Disorders

Article type: Review Article

Authors: Panza, Francesco^{a; b; 1; *} | Solfrizzi, Vincenzo^b | Sardone, Rodolfo^a | Dibello, Vittorio^{b; c} | Castellana, Fabio^a | Zupo, Roberta^a | Stallone, Roberta^d | Lampignano, Luisa^a | Bortone, Ilaria^a | Mollica, Anita^e | Berardino, Giuseppe^e | Ruan, Qingwei^{f; g} | Altamura, Mario^e | Bellomo, Antonello^e | Daniele, Antonio^{h; i} | Lozupone, Madia^{j; 1; *}

Affiliations: [a] Unit of Research Methodology and Data Sciences for Population Health, National Institute of Gastroenterology “Saverio de Bellis”, Research Hospital, Castellana Grotte, Bari, Italy | [b] “Cesare Frugoni” Internal and Geriatric Medicine and Memory Unit, University of Bari “Aldo Moro”, Bari, Italy | [c] Department of Orofacial Pain and Dysfunction, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam, The Netherlands | [d] Neuroscience and Education, Human Resources Excellence in Research, University of Foggia, Foggia, Italy | [e] Psychiatric Unit, Department of Clinical & Experimental Medicine, University of Foggia, Foggia, Italy | [f] Laboratory of Aging, Anti-aging & Cognitive Performance, Shanghai Institute of Geriatrics and Gerontology, Huadong Hospital, Fudan University, Shanghai, China | [g] Shanghai Key Laboratory of Clinical Geriatrics, Huadong Hospital, Shanghai Medical 14 College, Fudan University, Shanghai, China | [h] Department of Neuroscience, Catholic University of Sacred Heart, Rome, Italy | [i] Neurology Unit, IRCCS Fondazione Policlinico Universitario A. Gemelli, Rome, Italy | [j] Department of Translational Biomedicine and Neuroscience “DiBraiN”, University of Bari “Aldo Moro”, Bari, Italy

Correspondence: [*] Correspondence to: Francesco Panza, MD, PhD, Unit of Research Methodology and Data Sciences for Population Health, National Institute of Gastroenterology “Saverio de Bellis” Research Hospital, Castellana Grotte, Bari, Italy. E-mail: [email protected]; ORCID: 0000-0002-7220-0656 and Madia Lozupone, MD, PhD, Department of Translational Biomedicine and Neuroscience “DiBraiN”, University of Bari “Aldo Moro”, Bari, Italy. E-mail: [email protected]; ORCID: 0000-0002-1674-9724

Note: [1] These authors contributed equally to this work.

Abstract:  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.

Keywords: Alzheimer’s disease, cognitive frailty, dementia, frailty, lifestyle, mild cognitive impairment, physical frailty, social frailty, vascular dementia

DOI: 10.3233/JAD-230312

Journal: Journal of Alzheimer's Disease, vol. 94, no. 3, pp. 879-898, 2023