The physiologic complexity of prefrontal oxygenation dynamics is associated with age and executive function: an exploratory study.

BACKGROUND: The hemodynamics of prefrontal cortex (PFC) oxygenation are regulated by numerous processes operating over multiple temporal scales, producing complex patterns in its output fluctuations. Age may alter this multiscale regulation of PFC oxygenation, leading to diminished physiologic complexity of this important regulatory process. We aimed to characterize the effects of age on such complexity and its relationship to performance of an executive n-back task. METHODS: Twenty-four younger (aged 28±3 years) and 27 older (aged 78±6 years) adults completed this study. Continuous oxygenation (HbO2) and deoxygenation (HHb) signals of PFC were recorded using functional near-infrared-spectroscopy (fNIRS) while participants stood and watched a blank screen (blank), clicked a mouse when an X appeared (IdX) or when a letter was repeated from "2-back" in a sequence shown on a screen (2-back). We used multiscale entropy to quantify the HbO2 and HHb complexity of fNIRS signals. RESULTS: Older adults exhibited lower HbO2 and HHb complexity compared to younger adults, regardless of task (p=0.0005~0.002). Both groups exhibited greater complexity during the IdX and 2-back than blank task (p=0.02~0.04). Across all participants, those with greater HbO2 and/or HHb complexity during the blank task exhibited faster IdX and 2-back reaction time (ß=-0.56~-0.6, p=0.009~0.02). Those demonstrating greater increase of HbO2 and/or HHb complexity from IdX to 2-back task had lower percent increase in reaction time from IdX to 2-back task (ß=-0.41~-0.37, p=0.005~0.01). CONCLUSION: The complexity of fNIRS-measured PFC oxygenation fluctuations may capture the influence of aging on the regulation of prefrontal hemodynamics involved in executive-function-based task performance.

Extended effects of a wearable sensory prosthesis on gait, balance function and falls after 26 weeks of use in persons with peripheral neuropathy and high fall risk-The walk2Wellness trial.

Background: We recently reported that individuals with impaired plantar sensation and high fall risk due to sensory peripheral neuropathy (PN) improved gait and balance function following 10 weeks of use of Walkasins®, a wearable lower limb sensory prosthesis that provides directional specific mechanical tactile stimuli related to plantar pressure measurements during standing and walking (RxFunction Inc., Eden Prairie, MN, United States). Here, we report 26-week outcomes and compare pre- and in-study fall rates. We expected improvements in outcomes and reduced fall rates reported after 10 weeks of use to be sustained. Materials and methods: Participants had clinically diagnosed PN with impaired plantar sensation, high fall risk (Functional Gait Assessment, FGA score < 23) and ability to sense tactile stimuli above the ankle at the location of the device. Additional outcomes included 10 m Gait Speed, Timed Up and Go (TUG), Four-Stage Balance Test, and self-reported outcomes, including Activities-Specific Balance Confidence scale and Vestibular Disorders Activities of Daily Living Scale. Participants tracked falls using a calendar. Results: We assessed falls and self-reported outcomes from 44 individuals after 26 weeks of device use; 30 of them conducted in-person testing of clinical outcomes. Overall, improvements in clinical outcomes seen at 10 weeks of use remained sustained at 26 weeks with statistically significant increases compared to baseline seen in FGA scores (from 15.0 to 19.2), self-selected gait speed (from 0.89 to 0.97 m/s), and 4-Stage Balance Test (from 25.6 to 28.4 s), indicating a decrease in fall risk. Non-significant improvements were observed in TUG and fast gait speed. Overall, 39 falls were reported; 31 of them did not require medical treatment and four caused severe injury. Participants who reported falls over 6 months prior to the study had a 43% decrease in fall rate during the study as compared to self-report 6-month pre-study (11.8 vs. 6.7 falls/1000 patient days, respectively, p < 0.004), similar to the 46% decrease reported after 10 weeks of use. Conclusion: A wearable sensory prosthesis can improve outcomes of gait and balance function and substantially decreases incidence of falls during long-term use. The sustained long-term benefits in clinical outcomes reported here lessen the likelihood that improvements are placebo effects. Clinical trial registration: ClinicalTrials.gov, identifier #NCT03538756.

Diminished Locomotor Control Is Associated With Reduced Neurovascular Coupling in Older Adults.

BACKGROUND: Walking, especially while dual-tasking, requires functional activation of cognitive brain regions and their connected neural networks. This study examined the relationship between neurovascular coupling (NVC), as measured by the change in cerebral blood flow in response to performing a cognitive executive task, and dual-task walking performance. METHODS: Seventy community-dwelling older adults aged 84 ± 5 years within the Maintenance of Balance, Independent Living, Intellect and Zest in the Elderly (MOBILIZE) Boston Study were divided into LOW (n = 35) and HIGH (n = 35) NVC. NVC was quantified by transcranial Doppler ultrasound and stratified by the median change in cerebral blood flow velocity of the middle cerebral artery induced by the performance of the n-back task of executive function. Walking metrics included walking speed, step width, stride length, stride time, stride time variability, and double-support time from single- and dual-task walking conditions, as well as the "cost" of dual-tasking. RESULTS: During both single- and dual-task walking, older adults with LOW NVC displayed narrower step width (p = .02 and p = .02), shorter stride length (p = .01 and p = .02), and longer double-support time (p = .03 and p = .002) when compared with the HIGH group. During single-task walking only, LOW NVC was also linked to slower walking speed (p = .02). These associations were independent of age, height, hypertension, atrial fibrillation, and assistive device. The LOW and HIGH NVC groups did not differ in dual-task costs to walking performance. CONCLUSION: In older adults, diminished capacity to regulate cerebral blood flow in response to an executive function task is linked to worse walking performance under both single- and dual-task conditions, but not necessarily dual-task costs.

Multiscale Dynamics of Spontaneous Brain Activity Is Associated With Walking Speed in Older Adults.

BACKGROUND: In older adults, compromised white matter tract integrity within the brain has been linked to impairments in mobility. We contend that poorer integrity disrupts mobility by altering the processing of sensorimotor and cognitive and attentional resources in neural networks. The richness of information processing in a given network can be quantified by calculating the complexity of resting-state functional MRI time series. We hypothesized that (i) older adults with lower brain complexity, specifically within sensorimotor, executive, and attention networks, would exhibit slower walking speed and greater dual-task costs (ie, dual-task cost) and (ii) such complexity would mediate the effect of white matter integrity on these metrics of mobility. METHODS: Fifty-three older adults completed a walking assessment and a neuroimaging protocol. Brain complexity was quantified by calculating the multiscale entropy of the resting-state functional MRI signal within seven previously defined functional networks. The white matter integrity across structures of the corpus callosum was quantified using fractional anisotropy. RESULTS: Participants with lower resting-state complexity within the sensorimotor, executive, and attention networks walked more slowly under single- and dual-task (ie, walking while performing a serial-subtraction task) conditions (ß > 0.28, p ≤ .01) and had a greater dual-task cost (ß < -0.28, p < .04). Complexity in these networks mediated the influence of the corpus callosum genu on both single- (indirect effects > 0.15, 95% confidence intervals = 0.02-0.32) and dual-task walking speeds (indirect effects > 0.13, 95% confidence intervals = 0.02-0.33). CONCLUSION: These results suggest that the multiscale dynamics of resting-state brain activity correlate with mobility and mediate the effect of the microstructural integrity in the corpus callosum genu on walking speed in older adults.

Motor-Cognitive Neural Network Communication Underlies Walking Speed in Community-Dwelling Older Adults.

While walking was once thought to be a highly automated process, it requires higher-level cognition with older age. Like other cognitive tasks, it also becomes further challenged with increased cognitive load (e.g., the addition of an unrelated dual task) and often results in poorer performance (e.g., slower speed). It is not well known, however, how intrinsic neural network communication relates to walking speed, nor to this "cost" to gait performance; i.e., "dual-task cost (DTC)." The current study investigates the relationship between network connectivity, using resting-state functional MRI (rs-fMRI), and individual differences in older adult walking speed. Fifty participants (35 females; 84 ± 4.5 years) from the MOBILIZE Boston Study cohort underwent an MRI protocol and completed a gait assessment during two conditions: walking quietly at a preferred pace and while concurrently performing a serial subtraction task. Within and between neural network connectivity measures were calculated from rs-fMRI and were correlated with walking speeds and the DTC (i.e., the percent change in speed between conditions). Among the rs-fMRI correlates, faster walking was associated with increased connectivity between motor and cognitive networks and decreased connectivity between limbic and cognitive networks. Smaller DTC was associated with increased connectivity within the motor network and increased connectivity between the ventral attention and executive networks. These findings support the importance of both motor network integrity as well as inter-network connectivity amongst higher-level cognitive networks in older adults' ability to maintain mobility, particularly under dual-task (DT) conditions.

The pace and prognosis of peripheral sensory loss in advanced age: association with gait speed and falls.

BACKGROUND: Peripheral sensory loss is considered one of many risk factors for gait impairments and falls in older adults, yet no prospective studies have examined changes in touch sensation in the foot over time and their relationship to mobility and falls. Therefore, we aimed to determine the prevalence and progression of peripheral sensory deficits in the feet of older adults, and whether sensory changes are associated with the slowing of gait and development of falls over 5 years. METHODS: Using baseline, and 18 and 60 month followup data from the Maintenance Of Balance, Independent Living, Intellect, and Zest in the Elderly (MOBILIZE) Study in Boston, MA, we determined changes in the ability to detect stimulation of the great toe with Semmes Weinstein monofilaments in 351 older adults. We used covariate-adjusted repeated measures analysis of variance to determine relationships between sensory changes and gait speed or fall rates. RESULTS: Subjects whose sensory function was consistently impaired over 5 years had a significantly steeper decline in gait speed (- 0.23 m/s; 95% CI: -0.28 to - 0.18) compared to those with consistently intact sensory function (- 0.12 m/s; 95% CI: -0.15 to - 0.08) and those progressing from intact to impaired sensory function (- 0.13 m/s; - 0.16 to - 0.10). Compared to subjects with consistently intact sensation, those whose sensory function progressed to impairment during followup had the greatest risk of falls (adjusted risk ratio = 1.57 (95% confidence interval = 1.12 to 2.22). CONCLUSIONS: Our longitudinal results indicate that a progressive decline in peripheral touch sensation is a risk factor for mobility impairment and falls in older adults.

Compromised prefrontal structure and function are associated with slower walking in older adults.

Our previous work demonstrates that reduced activation of the executive network is associated with slow walking speed in a cohort of older adults from the MOBILIZE Boston Study. However, the influence of underlying white matter integrity on the activation of this network and walking speed is unknown. Thus, we used diffusion-weighted imaging and fMRI during an n-back task to assess associations between executive network structure, function, and walking speed. Whole-brain tract-based spatial statistics (TBSS) were used to identify regions of white matter microstructural integrity that were associated with walking speed. The integrity of these regions was then entered into multiple regression models to predict task performance and executive network activation during the n-back task. Among the significant associations of FA with walking speed, we observed the anterior thalamic radiation and superior longitudinal fasciculus were further associated with both n-back response speed and executive network activation. These findings suggest that subtle damage to frontal white matter may contribute to altered executive network activation and slower walking in older adults.

High levels of an endothelial dysfunction marker (sVCAM-1) are associated with injurious and recurrent falls and mortality over a 5-year interval in an older population.

We investigated the association between elevated plasma concentrations of circulating soluble Vascular Cell Adhesion Molecule-1 (sVCAM-1) and injurious falls and mortality over a 5-year period. We studied the prospective relationship between levels of circulating adhesion molecules and falls in 680 community-dwelling participants in the MOBILIZE Boston Study. The mean sVCAM-1 (±SD) concentration was 1192 ±â€¯428 ng/mL. Over 5-years of follow-up, 10.2% of participants died. The baseline sVCAM-1 (±SD) concentration was 1434 ±â€¯511 ng/mL in those who died vs. 1162 ±â€¯402 ng/mL in those who survived (P < 0.0001). sVCAM-1 level was associated with recurrent falls (P < 0.01); compared to the lowest quintile, the highest quintile of sVCAM-1 was associated with increased risk of injurious falls [multivariable adjusted Incidence Rate Ratio = 1.9, 95% CI (1.2-2.9), P = 0.009]. On survival analysis, the highest sVCAM-1 quintile was associated with the greatest mortality over 5 years (log-rank test, P < 0.0001). The adjusted hazard ratio was 2.4 [95% CI (2.1-2.7), P = 0.002]. High sVCAM-1 blood concentration was strongly associated with recurrent falls, injurious falls, and mortality in older adults.

The Complexity of Standing Postural Sway Associates with Future Falls in Community-Dwelling Older Adults: The MOBILIZE Boston Study.

Standing postural control is complex, meaning that it is dependent upon numerous inputs interacting across multiple temporal-spatial scales. Diminished physiologic complexity of postural sway has been linked to reduced ability to adapt to stressors. We hypothesized that older adults with lower postural sway complexity would experience more falls in the future. 738 adults aged ≥70 years completed the Short Physical Performance Battery test (SPPB) test and assessments of single and dual-task standing postural control. Postural sway complexity was quantified using multiscale entropy. Falls were subsequently tracked for 48 months. Negative binomial regression demonstrated that older adults with lower postural sway complexity in both single and dual-task conditions had higher future fall rate (incident rate ratio (IRR) = 0.98, p = 0.02, 95% Confidence Limits (CL) = 0.96-0.99). Notably, participants in the lowest quintile of complexity during dual-task standing suffered 48% more falls during the four-year follow-up as compared to those in the highest quintile (IRR = 1.48, p = 0.01, 95% CL = 1.09-1.99). Conversely, traditional postural sway metrics or SPPB performance did not associate with future falls. As compared to traditional metrics, the degree of multi-scale complexity contained within standing postural sway-particularly during dual task conditions- appears to be a better predictor of future falls in older adults.

Executive Network Activation is Linked to Walking Speed in Older Adults: Functional MRI and TCD Ultrasound Evidence From the MOBILIZE Boston Study.

BACKGROUND: Changes in cerebral blood flow velocity (CBF) in response to a cognitive task (task-related ΔCBF) have been shown by Transcranial Doppler ultrasonography (TCD) to be reduced in slow walkers. However, it is unknown whether reduced task-related ΔCBF is associated with reduced neural activity in specific brain regions, as measured by blood-oxygen-level dependent (BOLD) functional magnetic resonance imaging (fMRI). METHODS: We assessed the regional changes in neural activity associated with reduced middle cerebral artery (MCA) task-related ΔCBF to an executive task and slow walking speed in 67 community-dwelling older adults from the MOBILIZE Boston Study. Participants underwent walking assessments and TCD ultrasonography measures of MCA ΔCBF during the n-back task of executive function. A subset of participants (n = 27) completed the same task during fMRI. Individual BOLD activation maps for the n-back task were correlated with TCD measures and network-level averages were associated with TCD and preferred walking speed. RESULTS: Participants with diminished task-related ΔCBF walked more slowly (ß = .39, p = .001). fMRI revealed significant associations between task-related ΔCBF and regional BOLD activation in several brain regions/networks supplied by the MCA. Of these regions and networks, those within the executive network were most strongly associated with walking speed (ß = .36, p = .01). CONCLUSIONS: Task-related ΔCBF during an executive function task is related to activation in several neural networks and impairment in the ability to recruit the executive network in particular is associated with slow walking speed in older adults.

Functional implications of muscle co-contraction during gait in advanced age.

Older adults often exhibit high levels of lower extremity muscle co-contraction, which may be the cause or effect of age-related impairments in gait and associated falls. Normal gait requires intact executive function and thus can be slowed by challenging executive resources available to the neuromuscular system through the performance of a dual task. We therefore investigated associations between lower limb co-contraction and gait characteristics under normal and dual task conditions in healthy older adults (85.4±5.9years). We hypothesized that greater co-contraction is associated with slower gait speed during dual task conditions that stress executive and attentional abilities. Co-contraction was quantified during different phases of the gait cycle using surface electromyography (EMG) signals obtained from the anterior tibialis and lateral gastrocnemius while walking at preferred speed during normal and dual task conditions. Variables included the time difference to complete the Trail Making Test A and B (ΔTMT) and gait measures during normal or dual task walking. Higher co-contraction levels during the swing phase of both normal and dual task walking were associated with longer ΔTMT (normal: R2=0.25, p=0.02; dual task: R2=0.27, p=0.01). Co-contraction was associated with gait measures during dual task walking only; greater co-contraction levels during stride and stance were associated with slower gait speed (stride: R2=0.38, p=0.04; stance: R2=0.38, p=0.04), and greater co-contraction during stride was associated with longer stride time (R2=0.16, p=0.03). Our results suggest that relatively high lower limb co-contraction may explain some of the mobility impairments associated with the conduct of executive tasks in older adults.

Elevated Soluble Vascular Cell Adhesion Molecule-1 Is Associated With Cerebrovascular Resistance and Cognitive Function.

BACKGROUND: Elevated plasma soluble vascular cell adhesion molecule-1 (sVCAM-1) is a presumed marker of endothelial dysfunction, both in the brain and systemic circulation. Impairments in memory and cognition have been associated with cardiovascular diseases, but little is known about their relationships to abnormal cerebral endothelial function. METHODS: We studied the cross-sectional association between sVCAM-1 and markers of cerebrovascular hemodynamics and cognitive function in 680 community-dwelling participants in the MOBILIZE Boston Study, aged 65 years and older. Cognitive function was assessed using the Hopkins Verbal Learning Memory Test and Trail Making Tests (TMTs) A and B. Global cognitive impairment was defined as Mini-Mental State Examination (MMSE) score less than 24. sVCAM-1 was measured by ELISA assay. Beat-to-beat blood flow velocity (BFV) and cerebrovascular resistance (CVR = mean arterial pressure / BFV) in the middle cerebral artery were assessed at rest by transcranial Doppler ultrasound. RESULTS: sVCAM-1 concentrations were higher among participants with an MMSE score <24 versus ≥24 (1,201±417 vs 1,122±494ng/mL). In regression models adjusted for sociodemographic characteristics and health conditions, increasing levels of sVCAM-1 were linearly associated with higher resting CVR (p = .006) and lower performance on the Hopkins Verbal Learning Memory (immediate recall and delayed recall) and adjusted TMT B tests (p < .05). Higher levels of sVCAM-1 were also associated with global cognitive impairment on the MMSE (odds ratio = 3.9; 95% confidence interval: 1.4-10.9; p = .011). CONCLUSIONS: In this cohort of elderly participants, we observed a cross-sectional association between elevated sVCAM-1 levels and both cognitive impairment and increased cerebrovascular resistance. Longitudinal studies are needed to determine whether elevated sVCAM-1 is a cause or consequence of cerebrovascular damage.

Evaluation of an Automated Falls Detection Device in Nursing Home Residents.

OBJECTIVES: To determine the concordance between falls recorded using an investigational fall detection device and falls reported by nursing staff in a nursing home. DESIGN: Six-month prospective study. SETTING: Hebrew SeniorLife nursing home units in Boston, Massachusetts. PARTICIPANTS: Nursing home residents with a documented history of at least one fall within 12 months before consent (N = 62, mean age 86.2 ± 8.1, 66% female). INTERVENTION: Subjects continuously wore an automated falls detection device on a pendant around their neck. The device contained triaxial accelerometers set to detect a rapid change in position that was interpreted as a fall. MEASUREMENTS: Healthcare staff reported daily falls, defined as unexpected events in which residents were found on the floor, and the number of these falls was compared with the number of falls recorded according to the device. RESULTS: Seven of 37 residents whom nursing staff found on the floor had a fall recorded according to the device (19%). The device did not identify any of the clinical fall events in 23 of the 37 fallers (62%). The device detected 17 of 89 total falls that nursing staff recorded (sensitivity 19%) within an 8-hour time window. Of 128 fall events that the device recorded, 17 were concordant with nursing reports (13%) within an 8-hour time window, and 111 (87%) were false positives. CONCLUSION: There is poor concordance between falls recorded using the investigational fall detection device and falls to the floor that nursing home staff report.

Circulating vascular cell adhesion molecule-1 is associated with cerebral blood flow dysregulation, mobility impairment, and falls in older adults.

Soluble vascular cell adhesion molecule-1 (sVCAM-1) is associated with hypertension, vascular inflammation, and systemic endothelial dysfunction. We evaluated whether elevated plasma sVCAM-1 is associated with impaired cerebrovascular function and mobility impairments in elderly people. We studied the cross-sectional relationships between plasma sVCAM-1 level, gait speed, and cerebrovascular hemodynamics, and its longitudinal relationship with falls in 680 community-dwelling participants aged ≥65 years in the Maintenance of Balance, Independent Living, Intellect, and Zest in the Elderly (MOBILIZE) Boston Study. Falls were recorded prospectively for 1 year on daily calendars. sVCAM-1 was measured by ELISA assay and beat-to-beat blood flow velocity in the middle cerebral artery during rest and in response to changes in end-tidal CO2 was measured by transcranial Doppler ultrasound. sVCAM-1 concentration was 1094±340 ng/mL in normotensives, 1195±438 ng/mL in controlled hypertensives, and 1250±445 ng/mL in uncontrolled hypertensives (P=0.008). The mean resting blood flow velocity and cerebral vasomotor range were, respectively, 41.0±10.3 cm/s and 1.3±0.4 cm/s per millimeter of mercury. Elevated sVCAM-1 levels indicative of endothelial dysfunction were associated with reduced resting blood flow velocity (P=0.017) and cerebral vasomotor range (P=0.0048). Elevated sVCAM-1 levels were associated with slower gait speed (<0.8 m/s; odds ratio, 3.01; 95% confidence interval, 1.56-5.83; P=0.0011) and an increased odds of injurious falls (odds ratio, 2.4; 95% confidence interval, 1.4-4.2; P=0.0028). An elevated sVCAM-1 level may be a marker of cerebral blood flow dysregulation because of endothelial damage from hypertension. It may also signal the presence of cerebral microvascular disease and its clinical consequences, including slow gait speed and falls.

Reexamining the Effect of Antihypertensive Medications on Falls in Old Age.

Conflicting data on the relationship between antihypertensive medications and falls in elderly people may lead to inappropriate undertreatment of hypertension in an effort to prevent falls. We aimed to clarify the relationships between the chronic use of different classes of antihypertensive medications and different types of falls, to determine the effect of medication dose, and to assess whether the risk of falls is associated with differences in cerebral blood flow. We assessed demographics, clinical characteristics, and chronic antihypertensive medication use in 598 community-dwelling people with hypertension, aged 70 to 97 years, then followed them prospectively for self-reported falls using monthly calendar postcards and telephone interviews. Antihypertensive medication use was not associated with an increased risk of falls. Participants reporting use of angiotensin-converting enzyme inhibitors had a significantly decreased 1-year risk of injurious falls (odds ratio, 0.62; 95% confidence interval, 0.39-0.96), whereas those using calcium channel blockers had a decreased risk of all falls (odds ratio, 0.62; 95% confidence interval, 0.42-0.91) and indoor falls (odds ratio, 0.57; 95% confidence interval, 0.36-0.91), compared with participants not taking these drugs. Larger doses of these classes were associated with a lower fall risk. Participants taking calcium channel blockers had higher cerebral blood flow than those not taking these medications. In relatively healthy community-dwelling elderly people, high doses of antihypertensive agents are not associated with an increased risk of falls.

Patterns, predictors, and outcomes of falls trajectories in older adults: the MOBILIZE Boston Study with 5 years of follow-up.

BACKGROUND: Falls may occur as unpredictable events or in patterns indicative of potentially modifiable risks and predictive of adverse outcomes. Knowing the patterns, risks, and outcomes of falls trajectories may help clinicians plan appropriate preventive measures. We hypothesized that clinically distinct trajectories of falls progression, baseline predictors and their coincident clinical outcomes could be identified. METHODS: We studied 765 community-dwelling participants in the MOBILIZE Boston Study, who were aged 70 and older and followed prospectively for falls over 5 years. Baseline demographic and clinical data were collected by questionnaire and a comprehensive clinic examination. Falls, injuries, and hospitalizations were recorded prospectively on daily calendars. Group-Based Trajectory Modeling (GBTM) was used to identify trajectories. RESULTS: We identified 4 distinct trajectories: No Falls (30.1%), Cluster Falls (46.1%), Increasing Falls (5.8%) and Chronic Recurring Falls (18.0%). Predictors of Cluster Falls were faster gait speed (OR 1.69 (95CI, 1.50-2.56)) and fall in the past year (OR 3.52 (95CI, 2.16-6.34)). Predictors of Increasing Falls were Diabetes Mellitus (OR 4.3 (95CI, 1.4-13.3)) and Cognitive Impairment (OR 2.82 (95CI, 1.34-5.82)). Predictors of Chronic Recurring Falls were multi-morbidity (OR 2.24 (95CI, 1.60-3.16)) and fall in the past year (OR 3.82 (95CI, 2.34-6.23)). Symptoms of depression were predictive of all falls trajectories. In the Chronic Recurring Falls trajectory group the incidence rate of Hospital visits was 121 (95% CI 63-169) per 1,000 person-years; Injurious falls 172 (95% CI 111-237) per 1,000 person-years and Fractures 41 (95% CI 9-78) per 1,000 person-years. CONCLUSIONS: Falls may occur in clusters over discrete intervals in time, or as chronically increasing or recurring events that have a relatively greater risk of adverse outcomes. Patients with multiple falls, multimorbidity, and depressive symptoms should be targeted for preventive measures.

Enhanced vasoreactivity and its response to antihypertensive therapy in hypertensive elderly women.

Several previous studies have demonstrated sex differences in cardiovascular autonomic control in healthy young women, but little is known about the regulation of blood pressure in hypertensive elderly women, who have the greatest risk of adverse cardiovascular events. Therefore, we examined sex differences in physiological responses to upright tilt in 21 healthy (13 men and 8 women), 22 controlled hypertensive (10 men and 12 women), and 18 uncontrolled hypertensive (9 men and 9 women) elderly men and women. Of these, 19 normotensives, 18 controlled hypertensives, and 14 uncontrolled hypertensives completed 6 months of observation or pharmacological therapy for uncontrolled hypertension. All of the subjects underwent continuous monitoring of cardiac (RR) interval (ECG), finger arterial pressure (photoplethysmography), and stroke volume (transthoracic impedance) and periodic measurements of forearm blood flow (venous occlusion plethysmography) while resting supine and during a graded head-up tilt. Blood pressure and RR-interval power spectra were computed. Baroreflex gain was estimated by the cross-spectral and sequence methods. In contrast to other groups, elderly hypertensive women increased systemic vascular resistance during tilt. This response was associated with greater low-frequency systolic pressure variability, a presumed marker of sympathetic vascular control. After 6 months of successful antihypertensive therapy, women showed attenuation of the systemic vascular resistance response and a reduction in low-frequency systolic blood pressure variability to levels similar to men and normotensive controls. These results highlight the beneficial effects of antihypertensive therapy on the systemic vasculature, particularly for elderly women in whom enhanced vasoreactivity may contribute to excessive cardiovascular morbidity and mortality.

Antihypertensive therapy increases cerebral blood flow and carotid distensibility in hypertensive elderly subjects.

Many physicians are reluctant to lower blood pressure to recommended levels in elderly hypertensive patients because of concern about producing cerebral hypoperfusion. Because hypertension is associated with potentially reversible structural and functional alterations in the cerebral circulation that may improve with treatment, we investigated whether long-term pharmacological reduction of systolic blood pressure will improve, rather than worsen, cerebral blood flow and its regulation. Three groups of elderly subjects 65 years of age or older were studied prospectively: normotensive subjects (N=19), treated hypertensive subjects with systolic pressure <140 mm Hg (N=18), and uncontrolled hypertensive subjects with systolic pressure >160 mm Hg at entry into the study (N=14). We measured beat-to-beat blood flow velocity in the middle cerebral artery (transcranial Doppler ultrasonography), finger arterial pressure (photoplethysmography), and pulsatile distensibility of the carotid artery (duplex Doppler ultrasonography) at baseline and after 6 months of observation or antihypertensive therapy. After baseline hemodynamic measurements, uncontrolled hypertensive subjects underwent aggressive treatment with lisinopril with or without hydroclorothiazide or, if not tolerated, nifedipine or an angiotensin receptor blocker to bring their systolic pressure <140 mm Hg for 6 months. The other 2 groups were observed for 6 months. After 6 months of successful treatment, uncontrolled hypertensive subjects had significant increases in cerebral blood flow velocity and carotid distensibility that was not seen in the other groups. Treatment reduced cerebrovascular resistance and did not impair cerebral autoregulation. Therefore, judicious long-term treatment of systolic hypertension in otherwise healthy elderly subjects does not cause cerebral hypoperfusion.

Cerebral pressure-flow relations in hypertensive elderly humans: transfer gain in different frequency domains.

The dynamics of the cerebral vascular response to blood pressure changes in hypertensive humans is poorly understood. Because cerebral blood flow is dependent on adequate perfusion pressure, it is important to understand the effect of hypertension on the transfer of pressure to flow in the cerebrovascular system of elderly people. Therefore, we examined the effect of spontaneous and induced blood pressure changes on beat-to-beat and within-beat cerebral blood flow in three groups of elderly people: normotensive, controlled hypertensive, and uncontrolled hypertensive subjects. Cerebral blood flow velocity (transcranial Doppler), blood pressure (Finapres), heart rate, and end-tidal CO(2) were measured during the transition from a sit to stand position. Transfer function gains relating blood pressure to cerebral blood flow velocity were assessed during steady-state sitting and standing. Cerebral blood flow regulation was preserved in all three groups by using changes in cerebrovascular resistance, transfer function gains, and the autoregulatory index as indexes of cerebral autoregulation. Hypertensive subjects demonstrated better attenuation of cerebral blood flow fluctuations in response to blood pressure changes both within the beat (i.e., lower gain at the cardiac frequency) and in the low-frequency range (autoregulatory, 0.03-0.07 Hz). Despite a better pressure autoregulatory response, hypertensive subjects demonstrated reduced reactivity to CO(2). Thus otherwise healthy hypertensive elderly subjects, whether controlled or uncontrolled with antihypertensive medication, retain the ability to maintain cerebral blood flow in the face of acute changes in perfusion pressure. Pressure regulation of cerebral blood flow is unrelated to cerebrovascular reactivity to CO(2).

Effect of blood pressure on cognitive functions in elderly persons.

BACKGROUND: Little is known about what specific cognitive functions are affected by elevated blood pressure (BP) and how orthostatic BP change is related to cognitive impairment. The aim of this study was to determine the effect of BP and its postural change on cognitive functions in otherwise healthy elders. METHODS: In 70 healthy persons (mean age, 72 +/- 4 years), supine systolic BP (SBP) was assessed 3 times using a sphygmomanometer, and the average values were obtained for the analysis. After 1, 3, and 5 minutes of standing, 3 BP measurements were obtained and the orthostatic SBP changes were determined by subtracting these values from the supine average. Neuropsychological tests were administered to assess short-term and long-term verbal and visual memory, visuospatial skills, and frontal-executive functions. Participants were considered impaired in the specific cognitive performance if their scores fell below the 25th percentile of the study population. Multiple logistic regression models were used to evaluate the relation of SBP and the magnitude of orthostatic SBP decline to risk for impairment in each of the cognitive tests. RESULTS: Controlling for potential confounders, each 10 mmHg increase in supine SBP was associated with a 2.31-fold increase (95% confidence interval, 1.14 to 4.66) in risk for impairment in psychomotor speed and set shifting as measured using the Trailmaking Part-B test. There was no significant association between cognitive functions and orthostatic SBP decline at 1, 3, and 5 minutes of standing. CONCLUSION: Elevation of BP is associated with a selective impairment in executive function in otherwise healthy community-dwelling elders.