Participation in leisure activities has been associated with a lower risk of dementia. It is unclear whether increased participation in leisure activities lowers the risk of dementia or participation in leisure activities declines during the preclinical phase of dementia. We examined the relation between leisure activities and the risk of dementia in a prospective cohort of 469 subjects older than 75 years of age who resided in the community and did not have dementia at base line. We examined the frequency of participation in leisure activities at enrollment and derived cognitive-activity and physical-activity scales in which the units of measure were activity-days per week. Cox proportional-hazards analysis was used to evaluate the risk of dementia according to the base-line level of participation in leisure activities, with adjustment for age, sex, educational level, presence or absence of chronic medical illnesses, and base-line cognitive status. Over a median follow-up period of 5.1 years, dementia developed in 124 subjects (Alzheimer's disease in 61 subjects, vascular dementia in 30, mixed dementia in 25, and other types of dementia in 8). Among leisure activities, reading, playing board games, playing musical instruments, and dancing were associated with a reduced risk of dementia. A one-point increment in the cognitive-activity score was significantly associated with a reduced risk of dementia (hazard ratio, 0.93 [95 percent confidence interval, 0.90 to 0.97]), but a one-point increment in the physical-activity score was not (hazard ratio, 1.00). The association with the cognitive-activity score persisted after the exclusion of the subjects with possible preclinical dementia at base line. Results were similar for Alzheimer's disease and vascular dementia. In linear mixed models, increased participation in cognitive activities at base line was associated with reduced rates of decline in memory. Participation in leisure activities is associated with a reduced risk of dementia, even after adjustment for base-line cognitive status and after the exclusion of subjects with possible preclinical dementia. Controlled trials are needed to assess the protective effect of cognitive leisure activities on the risk of dementia.

Neurologic abnormalities affecting gait occur early in several types of non-Alzheimer's dementias, but their value in predicting the development of dementia is uncertain. We analyzed the relation between neurologic gait status at base line and the development of dementia in a prospective study involving 422 subjects older than 75 years of age who lived in the community and did not have dementia at base line. Cox proportional-hazards regression analysis was used to calculate hazard ratios with adjustment for potential confounding demographic, medical, and cognitive variables. At enrollment, 85 subjects had neurologic gait abnormalities of the following types: unsteady gait (in 31 subjects), frontal gait (in 12 subjects), hemiparetic gait (in 11 subjects), neuropathic gait (in 11 subjects), ataxic gait (in 10 subjects), parkinsonian gait (in 8 subjects), and spastic gait (in 2 subjects). During follow-up (median duration, 6.6 years), there were 125 newly diagnosed cases of dementia, 70 of them cases of Alzheimer's disease and 55 cases of non-Alzheimer's dementia (47 of which involved vascular dementia and 8 of which involved other types of dementia). Subjects with neurologic gait abnormalities had a greater risk of development of dementia (hazard ratio, 1.96 [95 percent confidence interval, 1.30 to 2.96]). These subjects had an increased risk of non-Alzheimer's dementia (hazard ratio, 3.51 [95 percent confidence interval, 1.98 to 6.24]), but not of Alzheimer's dementia (hazard ratio, 1.07 [95 percent confidence interval, 0.57 to 2.02]). Of non-Alzheimer's dementias, abnormal gait predicted the development of vascular dementia (hazard ratio, 3.46 [95 percent confidence interval, 1.86 to 6.42]). Among the types of abnormal gait, unsteady gait predicted vascular dementia (hazard ratio, 2.61), as did frontal gait (hazard ratio, 4.32) and hemiparetic gait (hazard ratio, 13.13). The presence of neurologic gait abnormalities in elderly persons without dementia at base line is a significant predictor of the risk of development of dementia, especially non-Alzheimer's dementia.

Background: Little is known in human immunodeficiency virus (HIV)–positive women about how the combination of plasma HIV RNA level and CD4 ⁺ T-cell count is associated with the natural history of human papillomavirus (HPV) infection or about HPV reactivation—whether it occurs and with what frequency in HIV-positive women. Methods: HIV-positive (n = 1848) and -negative (n = 514) women were assessed at semiannual visits (total person-years = 5661) for cervicovaginal HPV with polymerase chain reaction assays and for squamous intraepithelial lesions (SILs) by Pap smear. We studied the prevalent detection of HPV and SILs with generalized estimating equations and the incident detection and persistence of HPV and SILs with multivariable Cox models. All statistical tests were two-sided. Results: We observed a strong interaction between the associations of CD4 ⁺ and plasma HIV RNA strata with both prevalent ( P_interaction = .002) and incident ( P_interaction = .001) detection of HPV. Indeed, the hazard ratio for incident HPV detection peaked between 4.0 and 5.0, with either a CD4 ⁺ count of less than 200 cells per mm ³ or an HIV RNA level of more than 100 000 copies per mL. Although incident HPV detection in all women was associated with the number of recent sex partners ( P_trend <.001), 22% of sexually inactive HIV-positive women with a CD4 ⁺ count of less than 200 cells/mm ³ also had at least one incidently detected HPV type. The association between CD4 ⁺ /HIV RNA strata and HPV persistence was statistically significantly smaller ( P <.001) than for incident HPV detection. SIL prevalence, incident detection, and persistence had similar associations with CD4 ⁺ /HIV RNA strata as HPV (above). Conclusion: In HIV-positive women, plasma HIV RNA level and CD4 ⁺ count in combination appear to have a strong and statistically interactive association with incident detection of HPV, some of which may reflect HPV reactivation (e.g., in sexually inactive women). The more moderate association between HIV coinfection and HPV persistence could partly explain why cervical cancer rates have not reached more epidemic proportions in HIV-positive women.

In the Baltimore Longitudinal Study of Aging (BLSA), we examined the temporal unfolding of declining performance on tests of episodic memory (Free Recall on the Free and Cued Selective Reminding Test), executive function (Category Fluency, Letter Fluency, and Trails), and Verbal Intelligence (Nelson, 1982; American Version of the Nelson Adult Reading Test [AMNART]) before the diagnosis of dementia in 92 subjects with incident Alzheimer's disease (AD) followed for up to 15 years before diagnosis. To examine the preclinical onset of cognitive decline, we aligned subjects at the time of initial AD diagnosis and examined the cognitive course preceding diagnosis. We found that declines in performance on tests of episodic memory accelerated 7 years before diagnosis. Declining performance on tests of executive function accelerated 2–3 years before diagnosis, and verbal intelligence declined in close proximity to diagnosis. This cognitive profile is compatible with pathologic data suggesting that structures which mediate memory are affected earlier than frontal structures during the preclinical onset of AD. It also supports the view that VIQ as estimated by the AMNART does not decline during the preclinical onset of AD. (JINS, 2008, 14, 266–278.)Supported in part by grants AG017854, AG08325, AG03949, and AG16573 from the National Institutes of Health, and by the National Institute on Aging Intramural Research Program of the National Institutes of Health.