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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\u2013frailty 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\u2013frailty interplay in older age.<\/jats:p>","DOI":"10.1089\/rej.2014.1637","type":"journal-article","created":{"date-parts":[[2015,3,27]],"date-time":"2015-03-27T04:27:40Z","timestamp":1427430460000},"page":"389-412","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":131,"title":["Cognitive Frailty: A Systematic Review of Epidemiological and Neurobiological Evidence of an Age-Related Clinical Condition"],"prefix":"10.1177","volume":"18","author":[{"given":"Francesco","family":"Panza","sequence":"first","affiliation":[{"name":"Geriatric Unit & Laboratory of Gerontology and Geriatrics","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Solfrizzi","sequence":"additional","affiliation":[{"name":"University of Bari Aldo Moro","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Rosaria","family":"Barulli","sequence":"additional","affiliation":[{"name":"University of Bari Aldo Moro","place":["Italy"]},{"name":"University of Bari Aldo Moro","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Santamato","sequence":"additional","affiliation":[{"name":"University of Foggia","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Seripa","sequence":"additional","affiliation":[{"name":"Geriatric Unit & Laboratory of Gerontology and Geriatrics","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Pilotto","sequence":"additional","affiliation":[{"name":"Geriatric Unit & Laboratory of Gerontology and Geriatrics","place":["Italy"]},{"name":"Hospital S. 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