title: Cognitive Frailty: A Systematic Review of Epidemiological and Neurobiological Evidence of an Age-Related Clinical Condition.
abstract: Advancing age is the focus of recent studies on familial and sporadic Alzheimer's disease (AD), suggesting a prolonged pre-clinical phase several decades before the onset of dementia symptoms. Influencing some age-related conditions, such as frailty, may have an impact on the prevention of late-life cognitive disorders. Frailty reflects a nonspecific state of vulnerability and a multi-system physiological change with increased risk for adverse health outcomes in older age. In this systematic review, frailty indexes based on a deficit accumulation model were associated with late life cognitive impairment and decline, incident dementia, and AD. Physical frailty constructs were associated with late-life cognitive impairment and decline, incident AD and mild cognitive impairment, vascular dementia, non-AD dementias, and AD pathology in older persons with and without dementia, thus also proposing cognitive frailty as a new clinical condition with co-existing physical frailty and cognitive impairment in non-demented older subjects. Considering both physical frailty and cognitive impairment as a single complex phenotype may be central in the prevention of dementia and its subtypes with secondary preventive trials on cognitive frail older subjects. The mechanisms underlying the cognitive-frailty link are multi-factorial, and vascular, inflammatory, nutritional, and metabolic influences may be of major relevance. There is a critical need for randomized controlled trials of intervention investigating the role of nutrition and/or physical exercise on cognitive frail subjects with the progression to dementia as primary outcome. These preventive trials and larger longitudinal population-based studies targeting cognitive outcomes could be useful in further understanding the cognitive-frailty interplay in older age.
authors: 1 Geriatric Unit & Laboratory of Gerontology and Geriatrics , Department of Medical Sciences, IRCCS "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Foggia, Italy .
authors: Francesco
authors: F
authors: Panza
authors: 2 Geriatric Medicine-Memory Unit and Rare Disease Centre, University of Bari Aldo Moro , Bari, Italy .
authors: Vincenzo
authors: V
authors: Solfrizzi
authors: 3 Neurodegenerative Disease Unit, Department of Basic Medicine, Neuroscience, and Sense Organs, University of Bari Aldo Moro , Bari, Italy .|4 Department of Clinical Research in Neurology, University of Bari Aldo Moro , "Pia Fondazione Cardinale G. Panico", Tricase, Lecce, Italy .
authors: Maria Rosaria
authors: MR
authors: Barulli
authors: 5 Department of Physical Medicine and Rehabilitation,"OORR Hospital", University of Foggia , Italy .
authors: Andrea
authors: A
authors: Santamato
authors: 1 Geriatric Unit & Laboratory of Gerontology and Geriatrics , Department of Medical Sciences, IRCCS "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Foggia, Italy .
authors: Davide
authors: D
authors: Seripa
authors: 1 Geriatric Unit & Laboratory of Gerontology and Geriatrics , Department of Medical Sciences, IRCCS "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Foggia, Italy .|6 Geriatric Unit, Azienda ULSS 16 Padova, Hospital S. Antonio , Padova, Italy .
authors: Alberto
authors: A
authors: Pilotto
authors: 3 Neurodegenerative Disease Unit, Department of Basic Medicine, Neuroscience, and Sense Organs, University of Bari Aldo Moro , Bari, Italy .|4 Department of Clinical Research in Neurology, University of Bari Aldo Moro , "Pia Fondazione Cardinale G. Panico", Tricase, Lecce, Italy .
authors: Giancarlo
authors: G
authors: Logroscino
mesh_terms: D000375:Aging; D003072:Cognition Disorders / Q000503:physiopathology*; D006761:Hospitals; D006801:Humans; D008954:Models, Biological; D009446:Neurobiology; D010641:Phenotype