Hal H. Atkinson

Angiotensin-Converting Enzyme Inhibitors and Cognitive Decline in Older Adults With Hypertension: Results From the Cardiovascular Health Study

BACKGROUND Hypertension (HTN) is a risk factor for dementia, and animal studies suggest that centrally active angiotensin-converting enzyme (ACE) inhibitors (those that cross the blood-brain barrier) may protect against dementia beyond HTN control. METHODS Participants in the Cardiovascular Health Study Cognition Substudy with treated HTN and no diagnosis of congestive heart failure (n = 1054; mean age, 75 years) were followed up for a median of 6 years to determine whether cumulative exposure to ACE inhibitors (as a class and by central activity), compared with other anti-HTN agents, was associated with a lower risk of incident dementia, cognitive decline (by Modified Mini-Mental State Examination [3MSE]), or incident disability in instrumental activities of daily living (IADLs). RESULTS Among 414 participants who were exposed to ACE inhibitors and 640 who were not, there were 158 cases of incident dementia. Compared with other anti-HTN drugs, there was no association between exposure to all ACE inhibitors and risk of dementia (hazard ratio [HR], 1.01; 95% confidence interval [CI], 0.88-1.15), difference in 3MSE scores (-0.32 points per year; P = .15), or odds of disability in IADLs (odds ratio [OR], 1.06; 95% CI, 0.99-1.14). Adjusted results were similar. However, centrally active ACE inhibitors were associated with 65% less decline in 3MSE scores per year of exposure (P = .01), and noncentrally active ACE inhibitors were associated with a greater risk of incident dementia (adjusted HR, 1.20; 95% CI, 1.00-1.43 per year of exposure) and greater odds of disability in IADLs (adjusted OR, 1.16; 95% CI, 1.03-1.30 per year of exposure) compared with other anti-HTN drugs. CONCLUSIONS While ACE inhibitors as a class do not appear to be independently associated with dementia risk or cognitive decline in older hypertensive adults, there may be within-class differences in regard to these outcomes. These results should be confirmed with a randomized clinical trial of a centrally active ACE inhibitor in the prevention of cognitive decline and dementia.

Executive Function, Memory, and Gait Speed Decline in Well-Functioning Older Adults

BACKGROUND In community-dwelling older adults, global cognitive function predicts longitudinal gait speed decline. Few prospective studies have evaluated whether specific executive cognitive deficits in aging may account for gait slowing over time. METHODS Multiple cognitive tasks were administered at baseline in 909 participants in the Health, Aging, and Body Composition Study Cognitive Vitality Substudy (mean age 75.2 ± 2.8 years, 50.6% women, 48.4% black). Usual gait speed (m/s) over 20 minutes was assessed at baseline and over a 5-year follow-up. RESULTS Poorer performance in each cognitive task was cross-sectionally associated with slower gait independent of demographic and health characteristics. In longitudinal analyses, each 1 SD poorer performance in global function, verbal memory, and executive function was associated with 0.003-0.004 m/s greater gait speed decline per year (p =.03-.05) after adjustment for baseline gait speed, demographic, and health characteristics. CONCLUSIONS In this well-functioning cohort, several cognitive tasks were associated with gait speed cross-sectionally and predicted longitudinal gait speed decline. These data are consistent with a shared pathology underlying cognitive and motor declines but do not suggest that specific executive cognitive deficits account for slowing of usual gait in aging.

Predictors of combined cognitive and physical decline

Objectives: To determine the incidence and correlates of combined declines in cognitive and physical performance.

Reliability of the 400-m usual-pace walk test as an assessment of mobility limitation in older adults.

Objectives: To assess the test‐retest reliability of the 400‐m usual‐pace walk test (400‐MWT), and to determine whether the 4‐m walk test predicts inability to walk 400 m.

The Relationship Between Cognitive Function and Physical Performance in Older Women: Results From the Women’s Health Initiative Memory Study

BACKGROUND Cognitive function and physical performance are associated, but the common sequence of cognitive and physical decline remains unclear. METHODS In the Womens Health Initiative Memory Study (WHIMS) clinical trial, we examined associations at baseline and over a 6-year follow-up period between the Modified Mini-Mental State (3MS) Examination and three physical performance measures (PPMs): gait speed (meters/second), chair stands (number of stands in 15 seconds), and grip strength (kilograms). Using mixed models, we examined the baseline 3MS as predictor of change in PPM, change in the 3MS as predictor of change in PPM, and baseline PPM as predictors of 3MS change. RESULTS Among 1,793 women (mean age = 70.3 years, 89% white, and mean 3MS score = 95.1), PPM were weakly correlated with 3MS-gait speed: r = .06, p = .02; chair stands: r = .09, p < .001; and grip strength: r = .10, p < .001. Baseline 3MS score was associated with subsequent PPM decline after adjustment for demographics, comorbid conditions, medications, and lifestyle factors. For every SD (4.2 points) higher 3MS score, 0.04 SD (0.04 m/s) less gait speed and 0.05 SD (0.29 kg) less grip strength decline is expected over 6 years (p </= .01 both). Changes in 3MS and PPM were associated, particularly with chair stands and grip strength (p < .003 both). Baseline PPMs were not associated with subsequent 3MS change. CONCLUSIONS Baseline global cognitive function and change in global cognitive function were associated with physical performance change, but baseline physical performance was not associated with cognitive change in this cohort. These analyses support the hypothesis that cognitive decline on average precedes or co-occurs with physical performance decline.

Intensive Glycemic Control Is Not Associated With Fractures or Falls in the ACCORD Randomized Trial

OBJECTIVE Older adults with type 2 diabetes are at high risk of fractures and falls, but the effect of glycemic control on these outcomes is unknown. To determine the effect of intensive versus standard glycemic control, we assessed fractures and falls as outcomes in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) randomized trial. RESEARCH DESIGN AND METHODS ACCORD participants were randomized to intensive or standard glycemia strategies, with an achieved median A1C of 6.4 and 7.5%, respectively. In the ACCORD BONE ancillary study, fractures were assessed at 54 of the 77 ACCORD clinical sites that included 7,287 of the 10,251 ACCORD participants. At annual visits, 6,782 participants were asked about falls in the previous year. RESULTS During an average follow-up of 3.8 (SD 1.3) years, 198 of 3,655 participants in the intensive glycemia and 189 of 3,632 participants in the standard glycemia group experienced at least one nonspine fracture. The average rate of first nonspine fracture was 13.9 and 13.3 per 1,000 person-years in the intensive and standard groups, respectively (hazard ratio 1.04 [95% CI 0.86–1.27]). During an average follow-up of 2.0 years, 1,122 of 3,364 intensive- and 1,133 of 3,418 standard-therapy participants reported at least one fall. The average rate of falls was 60.8 and 55.3 per 100 person-years in the intensive and standard glycemia groups, respectively (1.10 [0.84–1.43]). CONCLUSIONS Compared with standard glycemia, intensive glycemia did not increase or decrease fracture or fall risk in ACCORD.

Cystatin-C as a Marker of Cognitive Function in Elders: Findings from the Health ABC Study

We determined whether serum cystatin C, a novel measure of kidney function that colocalizes with brain β‐amyloid, is associated with cognition among 3,030 elders. Those with high cystatin C (n = 445; 15%) had worse baseline scores on Modified Mini‐Mental State Examination or Digit Symbol Substitution Test (p ≤ 0.02) compared with those with intermediate/low level and 7 years greater decline (p ≤ 0.04). Incident cognitive impairment (decline ≥1.0 standard deviation) was greatest among those with high cystatin C (Modified Mini‐Mental State Examination: 38 vs 25%; adjusted odds ratio, 1.92; 95% confidence interval, 1.37–2.69; Digit Symbol Substitution: 38 vs 26%; odds ratio, 1.54; 95% confidence interval, 1.10–2.15). Ann Neurol 2008

Arterial Stiffness and Cognitive Decline in Well-Functioning Older Adults

BACKGROUND Stiffness of the central arteries in aging may contribute to cerebral microvascular disease independent of hypertension and other vascular risk factors. Few studies of older adults have evaluated the association of central arterial stiffness with longitudinal cognitive decline. METHODS We evaluated associations of aortic pulse wave velocity (centimeters per second), a measure of central arterial stiffness, with cognitive function and decline in 552 participants in the Health, Aging, and Body Composition (Health ABC) study Cognitive Vitality Substudy (mean age ± SD = 73.1 ± 2.7 years, 48% men and 42% black). Aortic pulse wave velocity was assessed at baseline via Doppler-recorded carotid and femoral pulse waveforms. Global cognitive function, verbal memory, psychomotor, and perceptual speed were evaluated over 6 years. RESULTS After adjustment for demographics, vascular risk factors, and chronic conditions, each 1 SD higher aortic pulse wave velocity (389 cm/s) was associated with poorer cognitive function: -0.11 SD for global function (SE = 0.04, p < .01), -0.09 SD for psychomotor speed (SE = 0.04, p = .03), and -0.12 SD for perceptual speed (SE = 0.04, p < .01). Higher aortic pulse wave velocity was also associated with greater decline in psychomotor speed, defined as greater than 1 SD more than the mean change (odds ratio = 1.42 [95% confidence interval = 1.06, 1.90]) but not with verbal memory or longitudinal decline in global function, verbal memory, or perceptual speed. Results were consistent with mixed models of decline in each cognitive test. CONCLUSIONS In well-functioning older adults, central arterial stiffness may contribute to cognitive decline independent of hypertension and other vascular risk factors.

Physical exercise and comorbidity. Results from the Fitness and Arthritis in Seniors Trial (FAST)

Background and aims: Physical exercise is associated with a lower risk of disability. The impact of comorbidity on the benefits from physical exercise has not been clearly investigated. Elders with comorbidity may benefit from physical exercise to preserve physical function. Methods: Data are from 435 participants with knee osteoarthritis aged ≥60 years enrolled in the Fitness and Arthritis in Seniors Trial (FAST), who were randomly assigned to 18-month health educational (HE), weight training (WT), or aerobic exercise (AE) interventions. Comorbidity was defined as the presence of osteoarthritis and ≥2 clinical conditions. Percent changes in the 6-minute walk test, self-reported disability and knee pain from baseline to 3-, 9-, and 18-month follow-up visits were analyzed according to comorbidity, using analysis of variance. Significances were adjusted using the Bonferroni method. Results: Mean age of the sample was 68.7 years. In participants with comorbidity (n=197), those in the AE intervention showed significant improvement in walking speed, compared to WT and HE groups, since the beginning of follow-up. Subjects with comorbidity in AE and WT groups showed improvement of the disability score at the 3-month follow-up visit compared to those in the HE group. This improvement was maintained at the end of the follow-up by the only AE group compared to the HE one (p=0.06). In participants with comorbidity, the pain score was improved by the AE intervention. Conclusions: AE and WT interventions improve physical function in individuals with comorbidity. AE improves physical function and knee pain independently of the presence of comorbidity.

Arterial Stiffness and Gait Speed in Older Adults With and Without Peripheral Arterial Disease

BACKGROUND Central arterial stiffness is increasingly recognized as an important predictor of cardiovascular events and mortality in older adults; however, few studies have evaluated the association of arterial stiffness with mobility decline, a common consequence of vascular disease. METHODS We analyzed the association of pulse wave velocity (PWV), a measure of aortic stiffness, with longitudinal gait speed over 7 years in 2,172 participants in the Health, Aging and Body Composition (ABC) Study (mean age ± s.d. 73.6 ± 2.9 years, 48% men, 39% black). RESULTS In mixed-effects models adjusted for demographics, each s.d. (396 cm/s) higher PWV was associated with 0.015 (s.e. 0.004) m/s slower gait at baseline and throughout the study period in the full cohort (P < 0.001); this relationship was largely explained by hypertension and other vascular risk factors. Among participants with peripheral arterial disease (PAD) (n = 261; 12.7%), each s.d. higher PWV was independently associated with 0.028 (s.e. 0.010) m/s slower gait speed at baseline and throughout the study period (P < 0.01). CONCLUSIONS These findings suggest that aortic stiffness may be especially detrimental to mobility in older adults with already compromised arterial function.