Hippocampal blood flow rapidly and preferentially increases after a bout of moderate-intensity exercise in older adults with poor cerebrovascular health.

Over the course of aging, there is an early degradation of cerebrovascular health, which may be attenuated with aerobic exercise training. Yet, the acute cerebrovascular response to a single bout of exercise remains elusive, particularly within key brain regions most affected by age-related disease processes. We investigated the acute global and region-specific cerebral blood flow (CBF) response to 15 minutes of moderate-intensity aerobic exercise in older adults (≥65 years; n = 60) using arterial spin labeling magnetic resonance imaging. Within 0-6 min post-exercise, CBF decreased across all regions, an effect that was attenuated in the hippocampus. The exercise-induced CBF drop was followed by a rebound effect over the 24-minute postexercise assessment period, an effect that was most robust in the hippocampus. Individuals with low baseline perfusion demonstrated the greatest hippocampal-specific CBF effect post-exercise, showing no immediate drop and a rapid increase in CBF that exceeded baseline levels within 6-12 minutes postexercise. Gains in domain-specific cognitive performance postexercise were not associated with changes in regional CBF, suggesting dissociable effects of exercise on acute neural and vascular plasticity. Together, the present findings support a precision-medicine framework for the use of exercise to target brain health that carefully considers age-related changes in the cerebrovascular system.

Feasibility of a Recumbent Stepper for Short-Interval, Low-Volume High-Intensity Interval Exercise in Stroke.

BACKGROUND AND PURPOSE: Studies investigating high-intensity interval exercise (HIIE) in stroke typically emphasize treadmill training. However, a literature review suggested that seated devices such as a recumbent stepper or cycle offer a promising alternative for HIIE since exercise can be prescribed using peak power output (PPO). Therefore, this would give health care professionals the ability to monitor and adapt power output for the target heart rate range. The purpose of this secondary analysis was to examine the feasibility of prescribing short-interval, low-volume HIIE using PPO in chronic stroke. METHODS: We used several methods to test feasibility: (1)Acceptability: Measured by the percentage of participants who completed the entire HIIE protocol; (2) Implementation was assessed by the number of reported cardiac or serious adverse events during submaximal exercise testing and HIIE and the average percentage of participants reaching vigorous intensity, defined by the American College of Sports Medicine as at least 77% of age-predicted maximal heart rate (HR max ). RESULTS: Data were available for 28 participants who were 32.2 (17.2) months post-stroke and 61.4 (11.9) years of age. Twenty-eight participants completed HIIE per protocol. No cardiac or serious adverse events occurred during the submaximal exercise test or during HIIE. The rapid switching between HIIE and recovery showed no evidence of blood pressure reaching unsafe thresholds. Average intensity during HIIE reached 76.8% HR max , which is slightly below the target of 77.0%. DISCUSSION AND CONCLUSIONS: A single bout of short-interval, low-volume HIIE, prescribed using PPO, was feasible in chronic stroke.Video Abstract : Available for more insights from the authors (Supplemental Digital Content, Video, available at: http://links.lww.com/JNPT/A474 ).

Aerobic Exercise Improves Cortical Inhibitory Function After Stroke: A Preliminary Investigation.

BACKGROUND AND PURPOSE: Aerobic exercise can elicit positive effects on neuroplasticity and cognitive executive function but is poorly understood after stroke. We tested the effect of 4 weeks of aerobic exercise training on inhibitory and facilitatory elements of cognitive executive function and electroencephalography markers of cortical inhibition and facilitation. We investigated relationships between stimulus-evoked cortical responses, blood lactate levels during training, and aerobic fitness postintervention. METHODS: Twelve individuals with chronic (>6 months) stroke completed an aerobic exercise intervention (40 minutes, 3×/wk). Electroencephalography and motor response times were assessed during congruent (response facilitation) and incongruent (response inhibition) stimuli of a Flanker task. Aerobic fitness capacity was assessed as o2peak during a treadmill test pre- and postintervention. Blood lactate was assessed acutely (<1 minute) after exercise each week. Cortical inhibition (N2) and facilitation (frontal P3) were quantified as peak amplitudes and latencies of stimulus-evoked electroencephalographic activity over the frontal cortical region. RESULTS: Following exercise training, the response inhibition speed increased while response facilitation remained unchanged. A relationship between earlier cortical N2 response and faster response inhibition emerged postintervention. Individuals who produced higher lactate during exercise training achieved faster response inhibition and tended to show earlier cortical N2 responses postintervention. There were no associations between o2peak and metrics of behavioral or neurophysiologic function. DISCUSSION AND CONCLUSIONS: These preliminary findings provide novel evidence for selective benefits of aerobic exercise on inhibitory control during the initial 4-week period after initiation of exercise training and implicate a potential therapeutic effect of lactate on poststroke inhibitory control.

Mixed circuit training acutely reduces arterial stiffness in patients with chronic stroke: a crossover randomized controlled trial.

PURPOSE: Investigate whether a single bout of mixed circuit training (MCT) can elicit changes in arterial stiffness in patients with chronic stroke. Second, to assess the between-day reproducibility of post-MCT arterial stiffness measurements. METHODS: Seven participants (58 ± 12 years) performed a non-exercise control session (CTL) and two bouts of MCT on separate days in a randomized counterbalanced order. The MCT involved 3 sets of 15 repetition maximum for 10 exercises, with each set separated by 45-s of walking. Brachial-radial pulse wave velocity (br-PWV), radial artery compliance (AC) and reflection index (RI1,2) were assessed 10 min before and 60 min after CTL and MCT. Ambulatory arterial stiffness index (AASI) was calculated from 24-h recovery ambulatory blood pressure monitoring. RESULTS: Compared to CTL, after 60 min of recovery from the 1st and 2nd bouts of MCT, lower values were observed for br-PWV (mean diff = - 3.9 and - 3.7 m/s, respectively, P < 0.01; ICC2,1 = 0.75) and RI1,2 (mean diff = - 16.1 and - 16.0%, respectively, P < 0.05; ICC2,1 = 0.83) concomitant with higher AC (mean diff = 1.2 and 1.0 × 10-6 cm5/dyna, respectively, P < 0.01; ICC2,1 = 0.40). The 24-h AASI was reduced after bouts of MCT vs. CTL (1st and 2nd bouts of MCT vs. CTL: mean diff = - 0.32 and - 0.29 units, respectively, P < 0.001; ICC2,1 = 0.64). CONCLUSION: A single bout of MCT reduces arterial stiffness during laboratory (60 min) and ambulatory (24 h) recovery phases in patients with chronic stroke with moderate-to-high reproducibility. TRIAL REGISTRATION: Ensaiosclinicos.gov.br identifier RBR-5dn5zd.

Health Promotion and Wellness in Neurologic Physical Therapy: Strategies to Advance Practice.

BACKGROUND AND PURPOSE: Neurologic physical therapy (PT) can assist people with neurologic conditions and injuries to optimize their health and well-being by addressing barriers at the individual, relationship, community, and societal levels. The purpose of this special interest article is to provide consensus-driven strategies to address barriers to implementing health promotion and wellness (HPW)-related neurologic PT practice. SUMMARY OF KEY POINTS: Environmental scan, literature review, and expert input were used to determine barriers and develop strategies. Barriers include lack of time; low knowledge, self-efficacy, and awareness; client complexity; and lack of HPW resources; as well as concerns regarding payment and scope of practice. Four key strategies emerged: (1) develop and disseminate a consensus-based scope of practice for HPW in neurologic PT; (2) increase knowledge of resources related to HPW; (3) promote delivery models for HPW-related neurologic PT; and (4) encourage advocacy, community building and partnership along the continuum of care. RECOMMENDATIONS FOR CLINICAL PRACTICE: Clinicians should practice to their full scope of HPW-related PT practice. This includes optimizing movement, including physical activity and fitness, as well as reinforcing the importance of healthy sleep, nutrition, stress, and smoking cessation. These activities address primary, secondary, and tertiary prevention. Clinicians are encouraged to report their experiences with HPW-focused delivery models and outcomes. Additional research is needed to understand the full impact of HPW on PT practice (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A364).

Statin contribution to middle cerebral artery blood flow velocity in older adults at risk for dementia.

PURPOSE: It is plausible that statins could improve cerebral blood flow through pleiotropic mechanisms. The purpose of this investigation was to assess the contribution of statins to cerebrovascular variables in older adults with dyslipidemia and familial history of dementia. Furthermore, we explored the interaction between statin use and sex due to prevalent bias in statin trials. METHODS: Middle cerebral artery blood flow velocity (MCAv) was measured using transcranial Doppler ultrasound. Continuous supine rest recordings lasted 8 min. Participants included in analyses were statin (n = 100) or non-statin users (n = 112). RESULTS: MCAv and cerebrovascular conductance were significantly higher in statin users (p = 0.047; p = 0.04), and pulsatility index (PI) was significantly lower in statin users (p < 0.01). An interaction effect between statin use and sex was present for PI (p = 0.02); female statin users had significantly lower cerebrovascular resistance than the other three groups. CONCLUSION: In this cross-sectional analysis, statin use was positively associated with cerebrovascular variables in older adults at risk for dementia. Female statin users had significantly higher resting MCAv and cerebrovascular conductance than female non-statin users. The greatest contribution of statin use was the association with reduced cerebrovascular resistance. Given that cerebrovascular dysregulation is one of the earliest changes in Alzheimer's disease and related dementia pathology, targeting the cerebrovasculature with statins may be a promising prevention strategy.

Hemispheric lateralization, endothelial function, and arterial compliance in chronic post-stroke individuals: A cross-sectional exploratory study.

Purpose/Aim: Cardiovascular function is controlled and regulated by a functional brain-heart axis. Although the exact mechanism is not fully understood, several studies suggest a hemispheric asymmetry in the neural control of cardiovascular function. Thus, the purpose of this study was to examine whether endothelial function and arterial compliance differ between individuals with left- and right-sided strokes.Materials and Methods: This was a cross-sectional exploratory study. Thirty individuals more than 6 months after stroke participated in the study. The endothelial function was assessed by ultrasound-measured flow-mediated dilation of the nonparetic arm brachial artery (baFMD). The arterial stiffness was assessed by measuring carotid-femoral pulse wave velocity (cfPWV) and central aortic pulse wave analysis [augmentation index (AIx), augmentation index normalized to a heart rate of 75 bpm (AIx@75) and reflection magnitude (RM)] using applanation tonometry. Results: Participants with right-sided stroke had worse endothelial function than those with left-sided stroke. This difference (baFMD = 2.51%) was significant (p = 0.037), and it represented a medium effect size (r = 0.38). Likewise, they had higher arterial stiffness than those with left-sided stroke. This difference (AIx = 10%; RM = 7%) was significant (p = 0.011; p = 0.012), and it represented a medium effect size (r = 0.48; r = 0.47).Conclusions: Our findings suggest that individuals with right-sided stroke have reduced endothelial function and arterial compliance compared to those with left-sided stroke. These data may indicate that those with right-sided strokes are more susceptible to cardiovascular events.

Primary Care of Adult Patients After Stroke: A Scientific Statement From the American Heart Association/American Stroke Association.

Primary care teams provide the majority of poststroke care. When optimally configured, these teams provide patient-centered care to prevent recurrent stroke, maximize function, prevent late complications, and optimize quality of life. Patient-centered primary care after stroke begins with establishing the foundation for poststroke management while engaging caregivers and family members in support of the patient. Screening for complications (eg, depression, cognitive impairment, and fall risk) and unmet needs is both a short-term and long-term component of poststroke care. Patients with ongoing functional impairments may benefit from referral to appropriate services. Ongoing care consists of managing risk factors such as high blood pressure, atrial fibrillation, diabetes, carotid stenosis, and dyslipidemia. Recommendations to reduce risk of recurrent stroke also include lifestyle modifications such as healthy diet and exercise. At the system level, primary care practices can use quality improvement strategies and available resources to enhance the delivery of evidence-based care and optimize outcomes.

Apolipoprotein E4 Moderates the Association Between Vascular Risk Factors and Brain Pathology.

BACKGROUND: The strongest genetic risk factor for late-onset Alzheimer disease (AD), Apolipoprotein E4 (APOE4), increases cardiovascular disease risk and may also act synergistically with vascular risk factors to contribute to AD pathogenesis. Here, we assess the interaction between APOE4 and vascular risk on cerebrovascular dysfunction and brain pathology. METHODS: This is an observational study of cognitively normal older adults, which included positron emission tomography imaging and vascular risk factors. We measured beat-to-beat blood pressure and middle cerebral artery velocity at rest and during moderate-intensity exercise. Cerebrovascular measures included cerebrovascular conductance index and the cerebrovascular response to exercise. RESULTS: There was a significant interaction between resting cerebrovascular conductance index and APOE4 carrier status on ß-amyloid deposition (P=0.026), with poor conductance in the cerebrovasculature associated with elevated ß-amyloid for the APOE4 carriers only. There was a significant interaction between non-high-density lipoprotein cholesterol and APOE4 carrier status (P=0.014), with elevated non-high-density lipoprotein cholesterol predicting a blunted cerebrovascular response to exercise in APOE4 carriers and the opposite relationship in noncarriers. CONCLUSIONS: Both cerebral and peripheral vascular risk factors are preferentially associated with brain pathology in APOE4 carriers. These findings provide insight into pathogenic vascular risk mechanisms and target strategies to potentially delay AD onset.

Optimizing Recruitment Strategies and Physician Engagement for Stroke Recovery Research.

BACKGROUND AND PURPOSE: A major challenge for stroke rehabilitation and recovery research is the recruitment and retention of participants. Our prior challenges and successes have influenced our team to rethink our approach and the potential for large-scale stroke recruitment. SUMMARY OF KEY POINTS: In this special interest article, we highlight how the adoption and implementation of recruitment strategies such as physician engagement and a streamlined "customer service" approach helped us improve our enrollment and maximize efficiency. Another positive outcome of enrollment was increased representation of those who identify as underrepresented minority or live in rural areas. RECOMMENDATIONS FOR CLINICAL PRACTICE: Rethinking our recruitment processes and infrastructure allowed for greater interprofessional interactions, minimal burden for our stroke physician team members, and maximized enrollment into our stroke studies.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A324).

Routine Assessment and Promotion of Physical Activity in Healthcare Settings: A Scientific Statement From the American Heart Association.

Physical inactivity is one of the most prevalent major health risk factors, with 8 in 10 US adults not meeting aerobic and muscle-strengthening guidelines, and is associated with a high burden of cardiovascular disease. Improving and maintaining recommended levels of physical activity leads to reductions in metabolic, hemodynamic, functional, body composition, and epigenetic risk factors for noncommunicable chronic diseases. Physical activity also has a significant role, in many cases comparable or superior to drug interventions, in the prevention and management of >40 conditions such as diabetes mellitus, cancer, cardiovascular disease, obesity, depression, Alzheimer disease, and arthritis. Whereas most of the modifiable cardiovascular disease risk factors included in the American Heart Association's My Life Check - Life's Simple 7 are evaluated routinely in clinical practice (glucose and lipid profiles, blood pressure, obesity, and smoking), physical activity is typically not assessed. The purpose of this statement is to provide a comprehensive review of the evidence on the feasibility, validity, and effectiveness of assessing and promoting physical activity in healthcare settings for adult patients. It also adds concrete recommendations for healthcare systems, clinical and community care providers, fitness professionals, the technology industry, and other stakeholders in order to catalyze increased adoption of physical activity assessment and promotion in healthcare settings and to contribute to meeting the American Heart Association's 2020 Impact Goals.

The Effect of Stroke on Middle Cerebral Artery Blood Flow Velocity Dynamics During Exercise.

BACKGROUND AND PURPOSE: Previous work demonstrates that older adults have a lower response in the middle cerebral artery velocity (MCAv) to an acute bout of moderate-intensity exercise when compared with young adults. However, no information exists regarding MCAv response to exercise after stroke. We tested whether MCAv response to an acute bout of moderate-intensity exercise differed between participants 3 months after stroke and an age- and sex-matched control group of older adults (CON). A secondary objective was to compare MCAv response between the stroke- and non-stroke-affected MCAv. METHODS: Using transcranial Doppler ultrasound, we recorded MCAv during a 90-second baseline (BL) followed by a 6-minute moderate-intensity exercise bout using a recumbent stepper. Heart rate (HR), end-tidal CO2 (PETCO2), and beat-to-beat mean arterial blood pressure (MAP) were additional variables of interest. The MCAv response measures included BL, peak response amplitude (Amp), time delay (TD), and time constant (τ). RESULTS: The Amp was significantly lower in the stroke-affected MCAv compared with CON (P < 0.01) and in the nonaffected MCAv compared with CON (P = 0.03). No between-group differences were found between TD and τ. No significant differences were found during exercise for PETCO2 and MAP while HR was lower in participants with stroke (P < 0.01). Within the group of participants with stroke, no differences were found between the stroke-affected and non-stroke-affected sides for any measures. DISCUSSION AND CONCLUSIONS: Resolution of the dynamic response profile has the potential to increase our understanding of the cerebrovascular control mechanisms and test cerebrovascular response to physical therapy-driven interventions such as exercise.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A284).

Effect of healthy aging and sex on middle cerebral artery blood velocity dynamics during moderate-intensity exercise.

Blood velocity measured in the middle cerebral artery (MCAV) increases with finite kinetics during moderate-intensity exercise, and the amplitude and dynamics of the response provide invaluable insights into the controlling mechanisms. The MCAV response after exercise onset is well fit to an exponential model in young individuals but remains to be characterized in their older counterparts. The responsiveness of vasomotor control degrades with advancing age, especially in skeletal muscle. We tested the hypothesis that older subjects would evince a slower and reduced MCAV response to exercise. Twenty-nine healthy young (25 ± 1 yr old) and older (69 ± 1 yr old) adults each performed a rapid transition from rest to moderate-intensity exercise on a recumbent stepper. Resting MCAV was lower in older than young subjects (47 ± 2 vs. 64 ± 3 cm/s, P < 0.001), and amplitude from rest to steady-state exercise was lower in older than young subjects (12 ± 2 vs. 18 ± 3 cm/s, P = 0.04), even after subjects were matched for work rate. As hypothesized, the time constant was significantly longer (slower) in the older than young subjects (51 ± 10 vs. 31 ± 4 s, P = 0.03), driven primarily by older women. Neither age-related differences in fitness, end-tidal CO2, nor blood pressure could account for this effect. Thus, MCAV kinetic analyses revealed a marked impairment in the cerebrovascular response to exercise in older individuals. Kinetic analysis offers a novel approach to evaluate the efficacy of therapeutic interventions for improving cerebrovascular function in elderly and patient populations. NEW & NOTEWORTHY Understanding the dynamic cerebrovascular response to exercise has provided insights into sex-related cerebrovascular control mechanisms throughout the aging process. We report novel differences in the kinetics response of cerebrovascular blood velocity after the onset of moderate-intensity exercise. The exponential increase in brain blood flow from rest to exercise revealed that 1) the kinetics profile of the older group was blunted compared with their young counterparts and 2) the older women demonstrated a slowed response.

Time Course of Flow-Mediated Dilation and Vascular Endothelial Growth Factor following Acute Stroke.

OBJECTIVES: People after stroke demonstrate alterations in vascular endothelial function measured by flow-mediated dilation. Limited information is available in the literature on possible protective factors following stroke. The aims of the secondary analysis were (1) to characterize the time course of vascular endothelial function using flow-mediated dilation at 72 hours after stroke and 1 week later during inpatient stroke rehabilitation and (2) to determine whether flow-mediated dilation was related to vascular endothelial growth factor, brain-derived neurotrophic factor, or estimated prestroke peak oxygen uptake. METHODS: Flow-mediated dilation using Doppler ultrasound was assessed in bilateral brachial arteries at the defined time points. Flow-mediated dilation and blood draws occurred on the same day between 7:30 am and 9:00 am following an overnight fast. Enzyme-linked immunosorbent assay was used to quantify plasma vascular endothelial growth factor and brain-derived neurotrophic factor values. A nonexercise estimate was used to calculate prestroke peak oxygen uptake. RESULTS: We have shown that between-limb differences are evident within 72 hours after stroke and remain 1 week later during inpatient rehabilitation. Higher values for vascular endothelial growth factor were associated with increased flow-mediated dilation at both time points. Higher estimated prestroke peak oxygen uptake was related to flow-mediated dilation. Brain-derived neurotrophic factor was not related to any outcome measures. CONCLUSIONS: Unique vascular adaptations start early after stroke in the stroke-affected limb and remain through inpatient stroke rehabilitation. Vascular endothelial growth factor and prestroke physical activity may have a protective role in vascular function following stroke. Future work should focus on mechanistic pathways for preservation of vascular health.

Aerobic exercise improves measures of vascular health in diabetic peripheral neuropathy.

AIMS: Aerobic exercise improves vascular endothelial function in people with Type 2 diabetes mellitus (T2DM). There is minimal information available regarding vascular health in people with T2DM and diabetic peripheral neuropathy (DPN). Thus, the primary aim of this secondary analysis was to determine whether a 16-week aerobic exercise intervention could improve vascular health in people with T2DM and DPN. A secondary aim was to explore the relationship between changes in flow-mediated dilation (FMD) and the number of years since diagnosis of DPN. METHODS: We examined whether a 16-week aerobic exercise intervention would improve vascular health in people with T2DM and DPN. We used Doppler ultrasound to assess brachial artery diameter and peak shear at baseline and post-exercise. Paired t-tests were used to determine whether the outcome measures improved from baseline to post-intervention. Pearson correlation assessed the relationship between DPN (years) and the percent change score (pre- to post-intervention) for FMD. RESULTS: Seventeen individuals were included in the data analysis. After the intervention, peak diameter increased (3.9 (0.5) to 4.0 (0.5) mm; p = 0.07). Time to peak shear occurred at 60.5 (24.6) seconds when compared to baseline at 68.2 (22.7) seconds; p = 0.17. We found that a longer duration (in years) of DPN demonstrated a fair, negative relationship (r = -0.41, p = 0.19) with the percent change in FMD. CONCLUSION: Aerobic exercise was beneficial for improving measures of vascular health but these were not statistically significant. The magnitude of change may be affected by the duration of DPN.

The relationship of pro-inflammatory markers to vascular endothelial function after acute stroke.

Purpose/Aim: Data from chronic stroke studies have reported reduced blood flow and vascular endothelial function in the stroke-affected limb. It is unclear whether these differences are present early after stroke. First, we investigated whether vascular endothelial function in the stroke-affected limb would be different from healthy adults. Second, we examined whether between-limb differences in vascular endothelial function existed in the stroke-affected arm compared to the non-affected arm. Last, we tested whether reduced vascular endothelial function was related to pro-inflammatory markers that are present early after stroke. MATERIALS AND METHODS: Vascular endothelial function was assessed by flow-mediated dilation (FMD) in the brachial artery within 72 h post-stroke. All participants withheld medications from midnight until after the procedure. Ultrasound scans and blood draws for pro-inflammatory markers occurred on the same day between 7:30 am and 9:00 am. RESULTS: People with acute stroke had significantly lower FMD (4.2% ± 4.6%) than control participants (8.5% ± 5.2%, p = 0.037). Stroke participants had between-limb differences in FMD (4.2% ± 4.6% stroke-affected vs. 5.3% ± 4.4% non-affected, p = 0.02), whereas, the control participants did not. Of the pro-inflammatory markers, only vascular cell adhesion molecule-1(VCAM-1) had a significant relationship to FMD (stroke-affected limb, r = -0.62, p = 0.03; non-affected limb, r = -0.75, p = 0.005), but not tumor necrosis factor alpha nor interleukin-6. CONCLUSIONS: Vascular endothelial function is reduced starting in the early stage of stroke recovery. People with higher levels of VCAM-1 had a lower FMD response.

Exercise Test Performance Reveals Evidence of the Cardiorespiratory Fitness Hypothesis.

Positive physiologic and cognitive responses to aerobic exercise have resulted in a proposed cardiorespiratory (CR) fitness hypothesis in which fitness gains drive changes leading to cognitive benefit. The purpose of this study was to directly assess the CR fitness hypothesis. Using data from an aerobic exercise trial, we examined individuals who completed cardiopulmonary and cognitive testing at baseline and 26 weeks. Change in cognitive test performance was not related to CR fitness change (r2 = .06, p = .06). However, in the subset of individuals who gave excellent effort during exercise testing, change in cognitive test performance was related to CR fitness change (r2 = .33, p < .01). This was largely due to change in the cognitive domain of attention (r2 = .36, p < .01). The magnitude of change was not explained by duration of exercise. Our findings support further investigation of the CR fitness hypothesis and mechanisms by which physiologic adaptation may drive cognitive change.

Cerebral ß-Amyloid Angiopathy Is Associated with Earlier Dementia Onset in Alzheimer's Disease.

BACKGROUND: Cerebral ß-amyloid angiopathy (CAA) occurs when ß-amyloid (Aß) is deposited in the vascular media and adventitia. It is a common pathology in the brains of older individuals and has been linked to cognitive decline, but relatively little is known about the influence that CAA has on the clinical manifestation of Alzheimer's disease (AD). The aim of this retrospective analysis was to quantify the effect that CAA had on the manifestation of initial AD-related cognitive change and subsequent progression of dementia. METHODS: We analyzed neuropathological data from the National Alzheimer's Coordinating Center's data set, performing parametric analyses to assess differences in age of progression to moderate-stage dementia. RESULTS: We found that individuals with both CAA burden and Aß neuritic plaque burden at death had the greatest risk of earlier conversion to very mild and moderate-stage dementia, but not necessarily faster progression. CONCLUSIONS: Our results suggest that CAA contributes to changes in early AD pathogenesis. This supports the idea that vascular change and neuritic plaque deposition are not just parallel processes but reflect additive pathological cascades that influence the course of clinical AD manifestation. Further inquiry into the role of CAA and its contribution to early cognitive change in AD is suggested.

Decrease in Insulin-Like Growth Factor-1 and Insulin-Like Growth Factor-1 Ratio in the First Week of Stroke Is Related to Positive Outcomes.

BACKGROUND: High insulin-like growth factor-1 (IGF-1), measured once during acute stroke, is associated with greater survival rates and lower stroke severity. However, information is lacking regarding how IGF-1 availability, determined by IGF-1's ratio to insulin-like growth factor binding protein-3 (IGFBP-3), relates to recovery and how the response of IGF-1 during the first week of stroke relates to outcomes. The purpose of this study was to determine the following: (1) the relationship between percent change in IGF-1 and IGF-1 ratio during the first week of stroke and stroke outcomes; and (2) the difference in percent change in IGF-1 and IGF-1 ratio in individuals being discharged home and individuals being discharged to inpatient facilities. METHODS: IGF-1 and IGFBP-3 were quantified from blood sampled twice (<72 hours of admission; 1 week post stroke) in 15 individuals with acute stroke. Length of stay, modified Rankin Scale at 1 month, and discharge destination were obtained from electronic medical records. RESULTS: Percent change in IGF-1 ratio was related to length of stay (r = .54; P = .04). Modified Rankin Scale (n = 10) was related to percent change in IGF-1 (r = .90; P < .001) and IGF-1 ratio (r = .75 P = .01). Individuals who went home (n = 7) had decreases in IGF-1 (-24 + 25%) and IGF-1 ratio (-36 + 50%), whereas individuals who went to inpatient facilities (n = 8) had increases in IGF-1 (37 + 46%) and IGF-1 ratio (30 + 40%). These differences were significant (IGF-1: P = .008; IGF-1 ratio: P = .01). CONCLUSION: Our findings suggest that a decrease in IGF-1 and IGF-1 ratio during the first week of stroke is associated with favorable outcomes: shorter length of stay, greater independence at 1 month on the modified Rankin Scale, and discharging home.