Blood Pressure Circadian Variation, Cognition and Brain Imaging in 90+ Year-Olds.

Purpose: To analyze the relationship between blood pressure (BP) variables, including circadian pattern, and cognition in 90+ year-olds. Methods: Twenty-four hour ambulatory BP monitoring was completed on 121 participants drawn from a longitudinal study of aging and dementia in the oldest-old. Various measures of BP and its variability, including nocturnal dipping, were calculated. Each person was given both a neuropsychological test battery covering different cognitive domains and a neurological examination to determine cognitive status. Seventy-one participants had a brain magnetic resonance imaging (MRI) scan. Results: Participants ranged in age from 90 to 102 years (mean = 93), about two-thirds were female, and nearly 80% had at least some college education. Mean nocturnal dips differed significantly between cognitively normal (n = 97) and impaired individuals (n = 24), with cognitively normal participants having on average greater nocturnal dips [6.6% vs. 1.3%, p = 0.006 for systolic BP (SBP); 11% vs. 4.4%, p = 0.002 for diastolic BP (DBP)]. Nocturnal dips were also related to performance on select cognitive test scores (especially those related to language, recent memory and visual-spatial ability), with individuals who performed below previously established median norms having significantly smaller nocturnal dips (both SBP and DBP) than those above the median. DBP reverse dippers had larger mean white matter hyperintensities (WMH as percent of total brain volume; 1.7% vs. 1.2%, 1.1% and 1.0% in extreme dippers, dippers, non-dippers) and a greater proportion had lobar cerebral microbleeds (CMBs; 44% vs. 0%, 7%, 16%, p < 0.05). Impaired participants had higher mean WMH than those with normal cognition (1.6% vs. 1.0% p = 0.03) and more tended to have CMB (31% vs. 20%, p = n.s.). Conclusion: These findings suggest that cognitive dysfunction is associated with dysregulation in the normal circadian BP pattern. Further study is warranted of the potential role of WHM and CMB as mediators of this association.

Age-related white matter integrity differences in oldest-old without dementia.

Aging is known to have deleterious effects on cerebral white matter, yet little is known about these white matter alterations in advanced age. In this study, 94 oldest-old adults without dementia (90-103 years) underwent diffusion tensor imaging to assess relationships between chronological age and multiple measures of integrity in 18 white matter regions across the brain. Results revealed significant age-related declines in integrity in regions previously identified as being sensitive to aging in younger-old adults (corpus callosum, fornix, cingulum, external capsule). For the corpus callosum, the effect of age on genu fractional anisotropy was significantly weaker than the relationship between age and splenium fractional anisotropy. Importantly, age-related declines in white matter integrity did not differ in cognitively normal and cognitively impaired not demented oldest-old, suggesting that they were not solely driven by cognitive dysfunction or preclinical dementia in this advanced age group. Instead, white matter in these regions appears to remain vulnerable to normal aging processes through the 10th decade of life.

Lower likelihood of falling at age 90+ is associated with daily exercise a quarter of a century earlier: The 90+ Study.

Objective: to explore the relationship between risk of falling at age 90+ and prior physical activity at age 60-70s. Design: population-based cohort study (The 90+ Study). Setting: California retirement community. Participants: of 1596 cohort members, 1536 had both falls and prior activity data. Mean age = 94 years; 78% female; 99% Caucasian. Methods: time spent in active physical activity was self-reported in 1980s; medical history, medication, assistive devices, residence type, and falls (outcome) was collected in 2000s. Activity/fall relationships were assessed using logistic regression. Results: falls were reported by 52% of participants, recurrent falls by 32%, and severe injury by 21% of fallers. In univariate analyses risk of falling at age 90+ was significantly related to medical history (heart disease, TIA/stroke, arthritis, vision disease, depression, dementia), medication use (hypnotics, anti-psychotics, anti-depressants), use of assistive devices (cane, walker, wheelchair), residence type (living with relatives, sheltered living), and source of information (self-report vs informant). Risks of falling and recurrent falls at age 90+ were 35-45% lower in those reporting 30+ minutes/day of active physical activity at age 60-70s compared with no activity. The odds ratio of falling was 0.65 (95% CI = 0.44-0.97) for 30-45 minutes/day and 0.64 (0.44-0.94) for 1+ hour/day adjusting for age, sex, medical history (stroke/TIA, vision disease, depression), use of assistive devices, and source of information. Conclusions and Relevance: falls are extremely common among the oldest-old and a significant proportion lead to severe injury. This work is the first to show an association between exercise at age 60-70s and lower risk of falling at age 90+.

Amyloid imaging and cognitive decline in nondemented oldest-old: the 90+ Study.

BACKGROUND: The goal of this study was to examine cross-sectional and longitudinal associations between cognitive performance and beta amyloid (Aß) load determined by florbetapir F18 positron emission tomography (PET) in nondemented oldest-old. METHODS: Thirteen nondemented (normal or cognitively impaired nondemented) participants (median age, 94.2 years) from The 90+ Study underwent florbetapir-PET scanning within 3 months of baseline neuropsychological testing. Amyloid load was measured with a semi-automated quantitative analysis of average cortical-to-cerebellar standardized uptake value ratio (SUVr) and a visual interpretation (Aß- or Aß+). Neuropsychological testing was repeated every 6 months. RESULTS: At baseline, SUVr correlated significantly with tests of global cognition and memory. During follow-up (median, 1.5 years), the Aß+ group had steeper declines on most cognitive tests, particularly global cognitive measures. CONCLUSION: This preliminary study suggests that greater amyloid load is associated with poorer cognition and faster cognitive decline in nondemented oldest-old. Amyloid load may identify individuals at increased risk of developing Alzheimer's disease.