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Background: Very few studies have investigated the impact of cognitive frailty in clinical settings, especially in memory clinic populations., Objective: To examine the impact of cognitive frailty on activities of daily living (ADL), cognitive function, and conversion to dementia among memory clinic patients with mild cognitive impairment (MCI)., Methods: The subjects of this retrospective study were 248 MCI patients (mean age, 76.3±5.4 years; females, 60.9%). All subjects completed a comprehensive geriatric assessment at baseline and at least one assessment during 3-year follow-up. Frailty was defined by generating a frailty index (FI), and MCI patients with frailty (FI≥0.25) were considered to represent cognitive frailty. As primary outcomes, the Barthel Index, Mini-Mental State Examination, and incident dementia were evaluated during follow-up. At baseline, patients were assessed for apolipoprotein E (APOE) phenotype. A linear mixed model, as well as a Cox proportional hazards regression model with adjustment for confounding variables, was performed., Results: Of these patients, 75 (30.2%) were classified as cognitive frail. APOEɛ4 carriers accounted for 26.7% of those with cognitive frailty and 44.5% of those without (p = 0.008). Cognitive frail patients showed a faster ADL decline (estimate, -1.04; standard error, 0.38; p = 0.007) than patients without cognitive frailty. Cognitive frailty was not associated with cognitive decline and incident dementia., Conclusion: Our findings demonstrated cognitive frailty increases the risk of dependence but not cognitive outcomes. Cognitive frailty may have heterogeneous conditions, including APOEɛ4-related pathologies, which may affect the cognitive trajectories of patients with MCI.

Background: Cognitive frailty (CF) is defined as simultaneous presence of physical frailty (PF) and cognitive impairment among older adults without dementia. Although white matter hyperintensities (WMH) as expressions of cerebral small vessel disease are associated with physical and cognitive decline and could manifest as CF, this association remains yet to be clarified., Objects: To clarify the association between CF and WMH among memory clinic patients., Methods: The subjects of this cross-sectional study were 121 cognitively normal (CN) and 212 mildly cognitively impaired (MCI) patients who presented to the Memory Clinic at the National Center for Geriatrics and Gerontology of Japan. PF status was defined based on the definition proposed by Fried and colleagues. CF was defined as simultaneous presence of pre-PF or PF and MCI. WMH volumes were measured using an automatic segmentation application. Multiple liner regression analyses with adjustment for cardiovascular risk factors were performed., Results: Of all subjects, 77 (63.6%) and 22 (18.2%) CN patients and 132 (62.3%) and 65 (30.7%) MCI patients were categorized into pre-PF and PF, respectively. Multiple liner regression analysis showed that those with CF had higher WMH volumes than those without (β= 0.23). When categorized into six groups according to PF and cognitive status, the PF/CN (β= 0.15), pre-PF/MCI (β= 0.41), and PF/MCI (β= 0.34) groups had higher WMH volumes than the non-PF/CN group., Conclusions: This study showed increased WMH volumes in CF and PF, indicating that WMH could be one of the key underlying brain pathologies of CF.

Objective: The aim of this study was to clarify the association of physical frailty with behavioral and psychological symptoms of dementia (BPSD) and caregiver burden in patients with Alzheimer's disease (AD)., Methods: The subjects were 1,193 AD patients who presented to the Memory Clinic at the National Center for Geriatrics and Gerontology of Japan during the period from October 2010 to February 2015 (mean ± SD age = 78.8 ± 6.3 years; female, 68.6%). AD was diagnosed based on the criteria of the National Institute on Aging and Alzheimer's Association workgroups. The Frailty Index (FI) was calculated as the ratio of actual to 38 potential deficits. BPSD and caregiver burden were assessed by using the Dementia Behavior Disturbance Scale (DBD) and the Japanese version of Zarit Burden Interview (J-ZBI). Multiple linear regression analyses and structural equation modeling (SEM) were performed to examine the relationship between the FI, DBD, and J-ZBI., Results: The subjects' mean FI score was 0.16 ± 0.10, with 663 (55.6%) and 198 (16.6%) subjects shown to be pre-frail (0.08 ≤ FI < 0.25) and frail (FI ≥ 0.25), respectively. Multiple linear regression analyses and SEM showed that the FI was independently associated with both DBD (β = 0.30, P < .001) and J-ZBI (β = 0.13, P < .001). Moreover, when the FI was considered as a categorical variable, even pre-frailty was associated with increased DBD score (β = 0.16, P < .001) and J-ZBI score (β = 0.09, P = .003)., Conclusions: The presence of not only physical frailty but also pre-frailty, as determined by the FI, could increase BPSD and caregiver burden in patients with AD., (© Copyright 2018 Physicians Postgraduate Press, Inc.)

Since the operational definition of "cognitive frailty" was first proposed in 2013 by the International Academy of Nutrition and Aging and the International Association of Gerontology and Geriatrics, several studies have been carried out using this cognitive frailty model. In this review, we examined the available clinical and epidemiological evidence for cognitive frailty. Despite its low prevalence (1.0-1.8%) in the community setting, cognitive frailty has been associated with a high risk of disability, poor quality of life, and death; while cognitive frailty appears to be associated with a high risk of dementia, there is no clear evidence for this association. Again, while the prevalence of cognitive frailty appears to have increased in the clinical setting, to date, very few studies evaluated the impact of cognitive frailty. While a new definition of cognitive frailty was proposed in 2015 to incorporate "reversible" and "potential reversible" subtypes, there is a paucity of epidemiological evidence to support this definition. In conclusion, there is no consensus on the definition of cognitive frailty for use in clinical and community settings or on which measures to be used for detecting cognitive impairment. Further study is required to formulate effective preventive strategies for disability in the elderly., (Copyright © 2018 Elsevier B.V. All rights reserved.)