Abstract
BackgroundFrailty is associated with poorer cognitive functioning among people with HIV. Frailty measures vary widely and the optimal measure for predicting HIV-associated neurocognitive disorders (HAND) is unclear. MethodsParticipants were 289 people with HIV, aged 50 years or older (mean age 59·6 years, SD 7·3; 87% male, 13% female), enrolled in University of California San Diego's HIV Neurobehavioral Research Program from 2014 to 2020. Frailty measurements included the Fried Phenotype criteria (0–5 symptoms: weight loss, exhaustion, low physical activity, slowness, weakness), the Rockwood Frailty Index (proportion of general and HIV-specific health deficits ranging from 0 [no deficits] to 1 [all 34 deficits]), and the Veterans Aging Cohort Study (VACS) Index 1.0. HIV-associated Neurocognitive Disorders (HAND) was diagnosed according to the Frascati criteria using a seven-domain neuropsychological test. Separate ANOVAs (ie, one for each frailty measure) were used to examine differences in frailty severity between HAND subgroups, and receiver operating characteristic (ROC) analyses evaluated sensitivity and specificity of each frailty measure to detect symptomatic HAND (mild neurocognitive disorder and HIV-associated dementia) from cognitively normal cases. FindingsParticipants diagnosed with HIV-associated dementia had higher rates of frailty than participants without HAND among all three frailty measures (p<0·05; ds>0·41). Significant differences in frailty severity were observed between no HAND and mild neurocognitive disorder (p<0·05; ds>0·48) as well as asymptomatic HIV-associated neurocognitive impairment and HIV-associated dementia (p<0·05; ds>0·53) when using the Fried Phenotype or the Rockwood Frailty Index, but not with the VACS Index. To detect people who were symptomatic from individuals who were cognitively normal, an optimal cutoff of at least 3 was identified for the Fried Frailty index (area under the curve [AUC] 0·71), with sensitivity of 37% and specificity of 92%; an optimal cutoff of at least 0·206 was identified for the Rockwood Frailty index (AUC 0·66), with sensitivity of 85% and specificity of 43%; and an optimal cutoff of at least 29 was identified for the VACS index (AUC 0·59), with sensitivity of 58% and specificity of 65%. InterpretationFried and Rockwood outperformed VACS in predicting HAND; however, ROC analyses suggest none of the indices had adequate predictive validity in detecting HAND. Given the Rockwood Index's overly inclusiveness (high sensitivity), we proposed it be used as a screening tool. When combined with the Frailty Index, which has demonstrated to be a good exclusionary tool (high specificity), the two measure can be clinically useful together in detecting HAND. FundingNational Institute of Mental Health (R01 MH099987, P30 MH062512), the National Institute on Drug Abuse (T32 DA031098 and F31AG064989), and the National Institute on Alcohol Abuse and Alcoholism (F31 AA027198).
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