Peripheral Arterial Disease and Cognitive Function
Waldstein, Shari R. PhD; Tankard, Carol F. MA; Maier, Karl J. MA; Pelletier, Jessica R. BA; Snow, Joseph PhD; Gardner, Andrew W. PhD; Macko, Richard MD; Katzel, Leslie I. MD, PhD
From the Department of Psychology, University of Maryland, Baltimore County (S.R.W., C.F.T, K.J.M., J.R.P., J.S.), Baltimore, MD; and Division of Gerontology, Department of Medicine, University of Maryland School of Medicine & Geriatric Research Education and Clinical Center, Baltimore Veterans Affairs Medical Center, (S.R.W., A.W.G., R.M., L.I.K.), Baltimore, MD.
Address reprints request to: Shari R. Waldstein, PhD, Department of Psychology, University of Maryland, Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21250. Email: firstname.lastname@example.org
Received for publication July 30, 2002; revision received January 22, 2003.
Objective: Peripheral arterial disease (PAD) is associated with comorbid atherosclerosis of the coronary and carotid arteries and is a significant risk factor for stroke. However, cognitive function in PAD patients before clinically evident stroke remains poorly characterized. Here we hypothesized that, on neuropsychological testing, PAD patients would perform more poorly than healthy control subjects, and persons with mild cardiovascular disease (essential hypertension), but better than stroke patients, thus reflecting a continuum of cognitive impairment associated with increased severity of vascular disease.
Method: The cognitive performance of 38 PAD patients (mean ankle-brachial index=0.67, Fontaine Class II) was contrasted with that of 23 healthy normotensive controls, 20 essential hypertensives, and 26 anterior ischemic stroke patients on twelve neuropsychological tests.
Results: PAD patients performed significantly more poorly than hypertensives and normotensives, but better than stroke patients, on seven tests of nonverbal memory, concentration, executive function, perceptuo-motor speed, and manual dexterity. Hypertensives displayed poorer performance than normotensives on tests of nonverbal memory and manual dexterity. These findings were independent of age, education, and depression scores. Higher diastolic blood pressure and plasma glucose levels predicted poorer performance of select cognitive tests by PAD patients. Eight to 67% of PAD patients displayed impaired performance (< 5th percentile of normotensive controls) on the seven aforementioned cognitive tests.
Conclusions: PAD patients exhibit diminished performance across a variety of domains of cognitive function. Findings also suggest a continuum of cognitive impairment associated with increasingly severe manifestations of cardiovascular disease, thus emphasizing the need for enhanced preventative measures to avert functional declines.
ABI = ankle-brachial index;, ANOVA = analysis of variance;, BDI = Beck Depression Inventory;, B-VAMC = Baltimore Veterans Affairs Medical Center;, DBP = diastolic blood pressure;, HSD = honestly significant difference;, MMSE = mini-mental status examination;, PAD = peripheral arterial disease;, PVD = peripheral vascular disease;, SBP = systolic blood pressure;, WMS-R = Wechsler Memory Scale-Revised.
Peripheral arterial occlusive disease (PAD), a common form of peripheral vascular disease (PVD), results from atherosclerosis of the arteries that supply the lower extremities (ie, abdominal aorta, iliac, femoral, popliteal, tibial). PAD affects approximately 16% of adults over the age of 55, including 10% asymptomatic PAD (stage I), 5% intermittent claudication (stage II), and 1% chronic leg ischemia (stages III–IV), and is a major cause of disability among older individuals (1). Revascularization may be utilized in stage III or IV PAD (ie, necrosis or gangrene), and stage IV disease may necessitate limb amputation.
As a diffuse atherosclerotic disease, PAD is associated with comorbid atherosclerosis of the coronary and carotid arteries (2). Indeed, risk for atherosclerotic events such as myocardial infarction, PAD, and stroke clusters among individuals (3–5), and PAD is considered a significant risk factor for stroke (6). However, cognitive function in PAD patients, before clinically evident stroke, remains poorly characterized. Atherosclerosis (7–9) and many of its risk factors such as hypertension (10–12), diabetes mellitus (13, 14), hyperlipidemia (13, 15), and cigarette smoking (16, 17), have known deleterious effects on cognitive function among stroke-free persons. As all of these conditions are highly prevalent among PAD patients (2), it is likely that cognitive deficits are also concomitants of this disease.
In this regard, several early investigations utilized PVD patients as control subjects in studies of the impact of various vascular surgeries, such as carotid endarterectomy and coronary artery bypass surgery, on cognitive function (18–20). Results of these studies suggested that patients with PVD displayed mild neuropsychological dysfunction (18, 19) or showed similar cognitive function as patients with carotid disease (20). In the first study to focus on PVD patients per se, severe cognitive impairment was noted in a subset of amputees (21). Affected functions among these Stage IV patients included short-term memory, attention, concentration, orientation, and judgment. However, no control group was employed.
More recently, Phillips and colleagues contrasted the cognitive performance of amputees secondary to PVD (stage IV) with that of healthy control subjects (22). Deficits among PVD patients were found on tests of perceptuo-motor speed and executive functions. Extending on this work, these authors examined a group of amputees and nonamputees with mild to moderate claudication, as compared with healthy control subjects, and atherothrombotic stroke patients (23). Results indicated that this spectrum of PVD patients performed more poorly than healthy controls on tests of attention, psychomotor speed, executive functions, visual memory, and visuospatial ability, but not verbal memory, language, or sensory-motor function. Furthermore, the performance of the PVD patients was, in many instances, similar to that of the stroke patients, although on several tests the stroke patients did more poorly. It was also noted that measures of PVD severity and presence of ischemic heart disease were significant predictors of cognitive performance among the PVD patients, although several cardiovascular risk factors were not.
In the population-based Rotterdam study, Breteler et al. (24) found that individuals having an ankle-brachial index (ABI) < 0.90 (diagnostic of PVD) displayed poorer performance on the Mini-Mental Status Examination (MMSE) than patients with greater ABIs. The presence of PVD, as assessed by ABI, has also been associated with cognitive decline on the MMSE and a test of perceptuo-motor speed over periods of three (25) and seven (26) years, particularly among individuals having an ApoE ε4 allelle. In contrast, Rao et al. (27) noted that nonamputee PVD patients performed similarly to a group of orthopedic controls (eg, hip or knee replacement). However, little information was provided about the PVD patients or the control subjects. Interpretation of these findings is further limited given the notable prevalence of cognitive impairment among such orthopedic patients (28, 29).
The present investigation extends on prior research in several ways. First, we examine a group of milder PAD patients, all presently classified as Stage II and all nonamputees. Second, whereas prior work included control subjects with medical conditions that might also affect cognitive function, the present control subjects were screened carefully for comorbidities. Third, we include two vascular disease comparison groups - anterior ischemic stroke patients and essential hypertensives. Pronounced cognitive impairment among stroke patients is well documented (30, 31), as are the more subtle cognitive consequences of hypertension (10–12). However, the groups examined herein have never been directly compared with respect to cognitive performance. Anterior stroke patients were chosen as controls because prior research suggests that milder forms of cardiovascular disease may have a particularly potent impact on cognitive functions that are associated with adequate functioning of anterior brain regions (32). It was hypothesized that a continuum of cognitive impairment would be noted in relation to increasingly severe manifestations of cardiovascular disease - hypertension, PAD, and stroke. Fourth, as noted previously by Phillips (23), it is of interest to examine the potential influence of medically assessed cardiovascular risk factors, measured as continuous variables, on cognitive performance within PAD patients. Prior work has utilized dichotomous measures of such variables.
MATERIALS AND METHODS
Thirty-eight older community-dwelling, stroke-free adults with PAD were recruited from ongoing PAD research protocols for participation in this study. All patients were classified as having Fontaine stage II PAD by the following criteria: (a) a positive Rose questionnaire for intermittent claudication (33); (b) intermittent claudication elicited during a screening treadmill test; and (c) an ABI at rest < 0.97, and an ABI <0.85 one minute after the graded treadmill test used to assess claudication (34, 35). The mean ABI was 0.67 (SD=0.48). Patients in the larger protocols were recruited from the vascular surgery clinics at the University of Maryland School of Medicine and the Baltimore Veterans Affairs Medical Center (B-VAMC), and via advertisements from the community. Study exclusions were leg pain while at rest, recent peripheral revascularization surgery for PAD (< 3 months), recent myocardial infarction (< 6 months), stroke, dementia, neurological disease, coronary artery bypass surgery, carotid endarterectomy, symptomatic angina during exercise treadmill testing, poorly controlled hypertension (>180/100 mm Hg), poorly controlled diabetes (fasting blood glucose > 200 mg/dl), severe dyslipidemia, renal or hepatic disease, psychiatric disorder, and heavy alcohol use.
Twenty-six ischemic stroke patients were recruited from a larger protocol investigating the impact of aerobic exercise intervention on recovery of function. Patients were randomized about equally to the active treatment and control arms of this study. However, all participants engaged in the present biomedical assessments and neuropsychological testing before beginning the exercise protocol. These patients had been recruited by referrals from local physicians, exercise physiologists, newspaper advertisement, and both inpatient and outpatient screenings at the local University, Veterans Affairs, and rehabilitation hospitals. All patients had stroke affecting the anterior circulation and reflecting involvement of the carotid territory (58% right-sided infarction; 42% left-sided infarction). Study exclusions were < 6 months post-stroke, dementia, other neurological disease affecting gait function, receptive or global aphasia, diagnosed Major Depression, poorly controlled diabetes, unstable cardiac disease, clinically apparent PAD (Fontaine Class II or greater), active cancer, pulmonary or renal failure, severe orthopedic conditions, uncontrolled hypertension (>/=160/100 mm Hg), chronic obstructive pulmonary disease, renal or hepatic disease, and heavy alcohol use.
Hypertensives and Normotensives
Twenty hypertensive and 23 normotensive patients were participating in a larger protocol examining the relation of hypertension to cognitive performance and brain structure and function. These stroke-free participants were recruited from the B-VAMC, the Geriatrics Research Education and Clinical Center, and by advertisement in the local community. Hypertensives met criteria for mild-to-moderate essential hypertension (36): systolic blood pressure (SBP)=140 to 180 mm Hg and/or diastolic blood pressure (DBP)=90 to 105 mm Hg upon clinical assessment or by prior physician diagnosis. Normotensives had SBP < 140 mm Hg and DBP < 90 mm Hg. Exclusionary criteria for both hypertensives and normotensives included history or clinical evidence of cardiovascular disease (other than hypertension among the hypertensive group), clinically apparent PAD (Fontaine Class II or greater), diabetes, other major medical disease (eg, renal, hepatic, pulmonary), neurological disease, stroke, dementia, psychiatric disorder, heavy alcohol use, or medications affecting central nervous system function. Participants taking antihypertensive medications had been weaned for at least two weeks before cognitive testing.
Sample characteristics for all groups are depicted in Table 1. All participants provided informed consent in accordance with the guidelines of the University of Maryland, Baltimore’s Institutional Review Board.
All participants first received a comprehensive medical evaluation including history, physical examination, blood chemistries, clinical assessment of blood pressure, a graded exercise treadmill test, and an oral glucose tolerance test. Blood pressure, lipids, and glucose were assessed while patients were taking their routine medications. Total plasma cholesterol and glucose levels were determined enzymatically. On a separate day, participants completed a neuropsychological test battery. Tests were selected for previously demonstrated sensitivity to vascular diseases including hypertension, PAD, and/or stroke (32), and to briefly assess the following domains of cognitive function: attention, working memory, verbal and nonverbal learning and memory, executive functions, visuospatial skills, motor speed, and manual dexterity. Language functions were not assessed because deficits on these tests are not typically associated with vascular disease diagnoses before stroke (32).
Attention and working memory were assessed by standard administration of the Digits Forward and Digits Backward portions of the Wechsler Adult Intelligence Scale -Revised (37), respectively. Verbal memory (immediate and 30 minutes delayed recall) was examined by recall of connected discourse using the Logical Memory subscale of the Wechsler Memory Scale -Revised (WMS-R) (38). Nonverbal memory (immediate and 30 minutes delayed recall) was evaluated by recall of geometric figures using the Visual Reproductions subscale of the WMS-R (38). Trail Making Test Parts A and B (39) and the Stroop Color-Word Test (40) assessed perceptuo-motor speed and executive functions (eg, mental flexibility, response inhibition). Part A of the Trail Making Test requires participants to draw a line connecting randomly arrayed, consecutively numbered circles as quickly as possible. In Part B, participants draw a line connecting consecutively numbered and lettered circles as quickly as possible by alternating between numbers and letters (ie, 1-A-2-B-3). The Stroop Color-Word Test requires participants to read aloud, as quickly as possible, from three pages. For Page 1, the participant reads a list of color names (ie, red, green, blue). For Page 2 the colors of inks (ie, red, green, blue) are named. Page 3 (the interference page) requires naming the color of the ink in which color names are printed in incongruent colors (ie, red printed in blue). The interference score was computed as per Golden’s criteria (40). Motor speed and manual dexterity were examined with the Grooved Pegboard Test (41) in which participants insert 25 pegs, as quickly as possible, into slotted holes that are angled in different directions on a pegboard, first with the dominant and then the nondominant hand. Visuospatial ability was evaluated with the Judgment of Line Orientation test (42). This test requires subjects to assess the configuration of lines drawn at different angles. Participants also completed the Beck Depression Inventory (BDI) (43) to assess depressive symptomatology.
Grooved Pegboard -Dominant and Nondominant hand data are missing for 3 and 13 stroke patients, respectively; these patients were unable to complete the test due to their hemiparesis. Grooved Pegboard and BDI data are missing for 8 and 9 PAD patients, respectively, due to late inclusion of these tests in the protocol. PAD and stroke patients completed the split-half version of the Judgment of Line Orientation test. Scores were doubled for analysis for comparability with the hypertensive and normotensive groups.
A series of one-way (diagnostic group) analyses of variance (ANOVAs) or chi-square analyses revealed that the groups were comparable with respect to education, gender, and total cholesterol levels (Table 1). However, the groups differed significantly with respect to age, SBP, DBP, glucose levels, smoking history, and BDI scores (p’s < 0.05). More specifically, PAD patients and hypertensives were significantly older than normotensives and stroke patients (who also differed from normotensives) (p’s <0.05). BDI scores were significantly higher in PAD and stroke patients than in hypertensives and normotensives (p’s <0.05). Normotensives had lower SBP and DBP than all other groups (p <0.05), and hypertensives had higher SBP than stroke patients, and higher DBP than PAD patients (p’s <0.05). PAD patients had higher glucose levels than all other groups (p’s<0.05), and the greatest proportion of current smokers.
One-way ANCOVAs (age and education as covariates) were used to contrast the neuropsychological performance of the PAD, stroke, hypertensive, and normotensive groups. Education was retained as a covariate despite the absence of significant group differences in this variable given its potent influence on cognitive function and the pronounced correlation with the majority of cognitive tests (up to r =0.46) in the present investigation. The Bonferroni correction was used to control for Type I error (significance level set at p <0.004). Tukey’s Honestly Significant Difference (HSD) was used to compute post-hoc analysis of group differences. Results (see Table 2) revealed significant group differences on Visual Reproductions - Immediate Recall (p <0.00001) and Delayed Recall (p =.003); Grooved Pegboard - Dominant Hand and Nondominant Hands (p’s<0.00001); Trail Making A (p <0.00001) and Trail Making B (p <0.00001); and Digits Backward (p <0.002). Tukey’s HSD tests revealed that PAD patients performed significantly more poorly than hypertensives and normotensives, but better than stroke patients on Visual Reproductions -Immediate Recall, both Grooved Pegboard tests, both Trail Making tests, 1 and Digits Backward (p’s<0.05); they also performed worse than normotensives on Visual Reproductions - Delayed Recall (p <0.05), and better than stroke patients on Visual Reproductions - Delayed Recall (p <0.05). In addition, hypertensives scored significantly more poorly than normotensives on Visual Reproductions - Immediate and Delayed Recall, and the Grooved Pegboard tests (p’s < 0.05). Tests with skewed score distributions (Grooved Pegboard, Trail Making A and B) were also analyzed following normalization with a log transformation. Results were comparable using transformed and raw scores. These analyses were also repeated with depression scores as an additional covariate using the subsample of PAD patients (N =29) who had BDI scores available. This yielded comparable results. 2
Next, to examine potential biomedical predictors of neuropsychological performance within PAD patients only, Pearson or point-biserial correlations were first computed between diagnostic variables (ie, history of diabetes, myocardial infarction, coronary artery disease, chronic obstructive pulmonary disease, hypertension, revascularization surgery, smoking history), medically assessed cardiovascular risk factors (ie, ABI, SBP, DBP, fasting plasma cholesterol and glucose), and the neuropsychological tests found to differ between PAD patients and the other groups. Age and education, which are potent influences on cognitive function, were partialed. Only those variables displaying significant partial correlations with cognitive measures were retained for subsequent multiple regression analyses: DBP, plasma glucose levels, smoking history.
To assess the multivariate relation of select cardiovascular risk factors (DBP, glucose, smoking history) to cognitive function (after controlling for age, education, and depression scores) within PAD patients, a series of hierarchical multiple regression analyses were computed in which each of these variables was forced into the equation. The following biomedical variables independently predicted poorer performance on three of the seven tests. For Visual Reproductions - Delayed Recall, plasma glucose levels (r2=0.15, p <0.02); for Grooved Pegboard - Dominant Hand, DBP (r2=0.19, p =.003); and for Grooved Pegboard - Nondominant Hand, DBP (r2=0.16, p <0.03).
Finally, consistent with prior research (23, 27), we estimated the degree of impairment exhibited by the vascular disease groups by computing the proportion of participants in each group who scored at or below the 5th percentile of performance displayed by the healthy normotensive group. These chi-square analyses were conducted only for the tests shown to differ among the diagnostic groups. As depicted in Table 3, a clear progression of impairment is apparent in the performance of the hypertensive, PAD, and stroke groups.
Results of the present investigation indicate that stage II PAD patients performed more poorly than healthy normotensives and mild-to-moderate essential hypertensives, but better than anterior ischemic stroke patients, on various tests of nonverbal memory, concentration, perceptuo-motor speed, manual dexterity, and executive function (ie, mental flexibility). In addition, hypertensives displayed poorer performance than normotensives on tests of nonverbal memory and manual dexterity. Group differences were not noted on other tests of basic attention, verbal memory, visuospatial ability, and executive function (ie, response inhibition). These results were independent of age, education, and depression scores. Overall, these findings suggest that cognitive performance may become progressively impaired with increasingly severe manifestations of cardiovascular disease. This conclusion is further supported by the finding that increasing proportions of patients in the hypertensive, PAD, and stroke groups exhibited impaired performance (</=5th percentile of normotensive controls).
These results are largely consistent with and extend on prior research. In this regard, both severe PAD patients (stage IV amputees) and a spectrum of PAD patients (mild to moderate claudicants and amputees) have previously been shown to exhibit comprised cognitive performance on tests of attention, perceptuo-motor speed, executive functions, visual memory, and visuospatial function (21–23). In one investigation, the performance of PAD patients was poorer than that of healthy normal controls, but largely similar to that of atherothrombotic stroke patients (23). The present findings extend this work to patients with milder PAD (intermittent claudication), and indicate that these patients also display fairly pronounced cognitive difficulties. Unlike Phillips (23), we found that PAD patients generally performed better than stroke patients. This may reflect the fact that our cohort had somewhat less severe PAD. As in the present investigation, pronounced cognitive deficits among stroke patients have been noted previously (30, 31), as has the performance differential between hypertensives and normotensives (10–12).
Phillips (23) previously noted that an index of PVD severity and history of ischemic heart disease predicted poorer cognitive performance within their PVD patients. However, these investigators examined patients with a broader spectrum of PVD and a greater proportion of heart disease than in the present sample. Here, our index of PAD severity, the ABI, and history of coronary artery disease or myocardial infarction did not correlate with cognitive performance in our group of PAD patients. The lack of association between ABI (presumably an indirect index of severity of atherosclerosis) and cognition may be due to our selection of patients with Fontaine Stage II disease and exclusion of patients with more severe PAD. In contrast, the present findings indicated that higher DBP and plasma glucose levels were associated with poorer performance on select tests of motor speed, manual dexterity, and delayed visual memory within PAD patients.
The mechanisms whereby PAD is associated with cognitive dysfunction remain unknown (44). However, several direct and indirect mechanisms are biologically plausible. First, as noted earlier, risk factors for atherosclerosis are generally the same for all arterial systems (2) and include dyslipidemia, diabetes, hypertension, and smoking. As noted above, both blood pressure and glucose levels were shown to impact within-group variability in performance among PAD patients. Furthermore, these factors have been associated with structural abnormalities in the brain on magnetic resonance imaging reflecting microvascular disease, indexes of macrovascular disease, brain atrophy, and diminished cerebral perfusion (for reviews see 10,11,44). Next, atherosclerosis in the carotid arteries, which is often comorbid with PAD (4, 5), has been related to decreased cognitive performance (7–9) perhaps by indirectly reducing cerebral perfusion. Atherosclerosis of the large intracerebral arteries may have similar effects. In addition, generalized atherosclerosis may be related to cognitive dysfunction via increased microemboli. We, and others, hypothesize that it is these structural changes in the brain, and the intracerebral and cervicocerebral arteries that mark the gradual emergence of cerebrovascular disease and that account for the diminished performance of PAD patients. However, few studies have examined the brains of PAD patients.
In this regard, PAD has been associated with white matter low attenuation (hypodense lesions) and atrophy on brain computerized tomography (45). In addition, mean ABIs were found to be significantly lower in patients with white matter lesions on magnetic resonance imaging in the Rotterdam Study (46). The presence of PAD was also associated with increased risk of white matter lesions. These findings are consistent with the fact that PAD is a risk factor for stroke (6). However, to date, neuroimaging has not been examined in conjunction with neuropsychological testing in PAD patients. As noted previously (23, 47), it is possible that those PAD patients who display the most pronounced cognitive deficits and silent brain disease are at greatest risk for future stroke or vascular dementia. It will be important, in future work, to assess brain morphology (using MRI) and the status of the intracerebral and cervicocerebral arteries (using carotid ultrasound or magnetic resonance angiography) in conjunction with neuropsychological testing in order to evaluate the brain mechanisms that underlie the cognitive dysfunction noted in these patients.
Phillips and colleagues have previously discussed potential clinical implications of cognitive deficits among PAD patients (23, 47). These investigators point out that, for amputees, the presence of cognitive deficits may affect rehabilitation efforts with prosthetic devices. More generally, cognitive difficulties may affect the ability of PAD patients to effectively follow complicated treatment regimens. Phillips (47) has also found that diminished visuospatial function, attention and memory predicted poorer everyday functioning among PVD patients at one-year follow-up. It is thus critical to further assess the impact of cognitive deficits on activities of daily living and functional status among PAD patients.
Several study limitations warrant comment. First, subjects underwent extensive medical evaluation before entry into their respective parent studies, and persons with poorly controlled medical comorbidities were generally excluded. Thus, the present results might not generalize to the larger patient populations. Second, hypertensive subjects were tapered off their standard antihypertensive medications before cognitive testing, whereas PAD and stroke patients were studied on their routine medications (for ethical reasons). It is therefore possible that medication use may have contributed, in part, to the impaired cognitive function in the PAD and stroke patients. Third, it is important to note that our neuropsychological battery provided only a brief sampling of select cognitive functions. The specific tests used also have certain limitations. For example, Digits Forward is a very gross measure of attention. In addition, it is likely that upper extremity paresis deleteriously affected stroke patients’ performance of tests requiring motor responding (eg, Trail Making Test, Grooved Pegboard, Visual Reproductions). Fourth, anterior stroke patients who are nonaphasic and who are willing and able to participate in an exercise intervention study may not be representative of the larger population of anterior stroke patients. Because they are likely to be more highly functioning, the performance differential between these stroke patients and the other three groups is probably underestimated. Fifth, it would have been useful to measure the ABI in all of our groups to further document their differential levels of severity with respect to vascular disease.
We suggest that future research in this area attend to several considerations. It would be useful to further characterize the performance of PAD patients using more extensive neuropsychological test batteries. It would also be helpful to examine whether PAD patients of increasing levels of severity (stages I –IV) display differences in the degree of cognitive difficulties. Use of neuroimaging procedures (eg, MRI, carotid ultrasound) in conjunction with cognitive testing will be important in elucidating the biological mechanisms underlying the cognitive impairments associated with PAD. Finally, future work should evaluate whether the diminished cognitive performance of PAD patients negatively affects their quality of life, activities of daily living, and ability to comply with medical regimens.
In sum, the results of the present investigation reveal a spectrum of cognitive difficulties among stage II PAD patients. An examination of the proportions of impaired patients displayed in Table 3 suggests that these difficulties range from mild to severe. The findings also suggest the existence of a continuum of cognitive impairment in patients with increasingly severe cardiovascular disease (ie, hypertension, PAD, stroke). These results highlight the need to enhance efforts in cardiovascular disease prevention and intervention to reduce cerebrovascular risk and potentially improve cognitive function and quality of life. Furthermore, consideration of cognitive deficits may be critical in planning medical regimens and rehabilitation efforts for PAD patients.
This work was supported by the Department of Veterans Affairs Baltimore Geriatric Research Education and Clinical Center; the University of Maryland Claude D. Pepper Older Americans Independence Center (NIA P60 AG12583); NIH grants R29 AG15112, R01 AG16685, R29 AG14487-01, K01 AG00657, and K24 AG00930; a VA Merit Grant; Bristol Myers Squibb Medical Imaging, Inc.; and the Geriatrics and Gerontology Education and Research Program of the University of Maryland, Baltimore.
1Analysis of the difference score between Trail Making A and B yielded a comparable pattern of significant findings thus suggesting that mental flexibility was affected rather than just response speed. Cited Here...
2After covarying age, education, and depression scores, the F and p values associated with the tests that previously differed significantly among the groups (after covarying just age and education) were as follows: Visual Reproductions -Immediate Recall (F=12.01, p <0.00001); Visual Reproductions -Delayed Recall (F=5.81, p =.001); Grooved Pegboard -Dominant Hand (F=13.2, p <0.00001); Grooved Pegboard -Nondominant Hand (F=15.4, p <0.00001); Trail Making A (F=10.67, p <0.00001); Trail Making B (F=10.15; p <0.00001); Digits Backward (F=5.84, p =.001). All other results remained nonsignificant. Cited Here...
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peripheral arterial disease,; cardiovascular disease,; hypertension,; stroke,; cognitive function,; neuropsychology.
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