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(Stroke. 1997;28:777-784.)
© 1997 American Heart Association, Inc.

Articles

Cognitive Deficits in Peripheral Vascular Disease

A Comparison of Mild Stroke Patients and Normal Control Subjects

Natalie A. Phillips, PhD C. Charles Mate-Kole, PhD

From the Department of Psychology, Concordia University, Montreal, Quebec (N.A.P.); and the Department of Psychology, Central Connecticut State University (New Britain) (C.M.-K.).

	Abstract

Top Abstract Introduction Subjects and Methods Results Discussion Appendix 1 References

 
Background and Purpose Evidence indicates that peripheral vascular disease (PVD) and cerebrovascular disease (CVD) coexist and therefore reflect a generalized pattern of atherosclerotic disease in an individual. Given the known deleterious effects of CVD on cognitive function, it was hypothesized that patients with PVD may have impaired cerebral function due to concomitant but clinically unrecognized CVD. The purpose of this study was to determine whether neuropsychological tests would reveal this potential dysfunction.

Methods Neuropsychological test scores (n=25) were compared across three groups: (1) 29 PVD patients (13 amputees, 16 nonamputees), (2) 29 age- and education-matched patients with atherothrombotic brain infarcts (ie, CVD), and (3) 30 age- and education-matched control subjects.

Results PVD patients performed significantly worse (P<.002) than control subjects on eight neuropsychological measures of executive function, attention, and visuospatial function. The pattern and, in certain instances, the magnitude of impairment was highly similar between PVD and CVD subjects. Regression analyses revealed that PVD severity and ischemic heart disease were significant negative predictors of test performance. Depression and atherosclerotic risk factors did not explain neuropsychological deficits after the effects of PVD and ischemic heart disease were considered.

Conclusions PVD patients exhibit neuropsychological deficits that suggest the presence of mild vascular-related brain dysfunction. Patients with multiple manifestations of generalized atherosclerosis (ie, severe PVD, ischemic heart disease) appear to be particularly at risk. Clinicians should be alert to these potential deficits and to the possibility of further vascular-related cognitive decline.

Key Words: neuropsychological tests • atherosclerosis • cognition • peripheral vascular disease

	Introduction

Top Abstract Introduction Subjects and Methods Results Discussion Appendix 1 References

 
This study investigated cognitive function in patients with PVD due to atherosclerosis (more precisely, chronic atherosclerotic occlusive disease of the lower-extremity arteries¹ ). Atherosclerosis is the most common cause of ischemia in the periphery¹ and central nervous system² ; thus, it is reasonable to suspect an association between arterial disease in the central nervous system and the periphery. CVD is viewed as a consequence of a long-term atherosclerotic process.³

Evidence indicating that PVD and CVD coexist suggests that the two reflect a generalized pattern of atherosclerotic disease in an individual. PVD is a risk factor for minor ischemic strokes and TIAs.⁴ PVD prevalence is significantly higher in patients with TIAs than in those without.⁵ After accounting for increasing number of TIAs and age, PVD was shown to be the third most predictive adverse factor influencing stroke outcome in TIA patients.⁶ It has been suggested that the presence of PVD should be considered a strong marker of generalized atherosclerosis.⁷

The deleterious effects of stroke (ie, CVD) on cognitive function are well known.⁸ Given the association between PVD and CVD and the effect of CVD on cognitive function, it is reasonable to suspect that PVD patients might also suffer impairment in cognitive function due to concomitant CVD. It is possible that at least some proportion of PVD patients have experienced subclinical or "silent" cerebral ischemic episodes that have either gone unrecognized by the patient, family, and/or medical practitioner or merely been attributed to the vagaries of aging. Neuropsychological measures would be sensitive to this potential brain dysfunction.

Little is known about the neuropsychological function of PVD patients. Some studies have included PVD patients as control subjects in examination of neuropsychological function before and after surgery (eg, after carotid endarterectomy to control for practice effects). Although evidence of at least mild neuropsychological dysfunction has been coincidentally observed (eg, see References 9 through 12^{9 10 11 12} ), these studies were not designed to assess this patient group per se, limiting the information that might be drawn from them. We¹³ specifically examined neuropsychological performance in patients with lower-extremity amputations secondary to PVD (who were considered free of neurological disease) and in age- and education-matched control subjects. By use of a comprehensive neuropsychological battery, it was shown that the PVD patients performed significantly worse than control subjects on certain measures of attention, psychomotor speed, and executive function, suggesting the presence of cerebral dysfunction.

Regardless of the arterial system involved, the risk factors for atherosclerotic development are the same: hyperlipidemia,² diabetes mellitus,² cigarette smoking,² hypertension,² increasing age,¹ and male sex.¹ Studies have indicated evidence of subtle neuropsychological dysfunction in patients with these risk factors.^{14 15}

In otherwise healthy hypertensive subjects, the most consistent finding is that of mild impairment on tests of psychomotor integrity and/or tests requiring rapid responding.^{16 17} Several studies have noted mild memory impairment.^{17 18 19} Visuospatial processes may also be affected.^{17 18}

Subtle neuropsychological deficits in type I diabetic persons have been observed on tests of visuospatial constructional ability²⁰ and reaction time.^{21 22} Several studies have demonstrated deficits in memory,^{20 22 23} while others have not.^{24 25} Studies of usually older patients with type II diabetes have yielded more consistent findings of impairment in reaction time,²² attention,^{22 26 27 28} and memory.^{22 26 27 28}

One study examined the effects of smoking in healthy elderly adults tested on a variety of neuropsychological measures.²⁹ The only differences between subjects who smoked and subjects who were nonsmokers or ex-smokers were found on tests of psychomotor speed.

Although we¹³ demonstrated that PVD amputees showed cognitive deficits when compared with normal control subjects, several questions remain. First, it is not known whether these findings are specific only to PVD amputees or are representative of patients with peripheral atherosclerosis in general. Second, it could not be inferred that the deficits were the result of underlying CVD because the PVD patients were not compared with a group with demonstrable CVD. Third, it is not known whether cognitive impairment is related to PVD per se or whether the deficits can be accounted for by the neurobehavioral effects of the various atherosclerotic risk factors found in many PVD patients.

To address these questions, the following hypotheses were tested in the present study: (1) PVD patients, as a whole, exhibit impaired neuropsychological function compared with age- and education-matched control subjects. (2) Patients with symptomatic PVD suffer from concurrent CVD and therefore will exhibit a pattern of neuropsychological impairment similar to that observed in a group of patients with CVD. (3) The severity of PVD will be the single best predictor of impaired cognitive performance. After this factor, it was hypothesized that variables reflecting other manifestations of atherosclerotic disease would be significantly related to cognitive deficits and would be stronger predictors than atherosclerotic risk factors.

	Subjects and Methods

Top Abstract Introduction Subjects and Methods Results Discussion Appendix 1 References

 
Subjects
PVD Patients
Nonamputee PVD patients. Sixteen patients (Table 1) with PVD were recruited from a noninvasive vascular diagnostic laboratory. The inclusion criterion was the positive identification of lower-extremity vascular insufficiency (ie, ankle/brachial pressure index <0.8).

View this table: [in this window] [in a new window]   Table 1. Summary of Demographic Factors for PVD, CVD, and Normal Control Subjects

Exclusion criteria included (1) vascular insufficiency secondary to trauma or nonatherosclerotic in nature, (2) history of completed stroke, (3) history of neurological disorder that could influence cognitive status, (4) history of major psychiatric disorder, (5) history of alcohol and/or drug abuse, or (6) history of significant medical disease (eg, renal, pulmonary) that might negatively affect cognitive function.

Amputee PVD patients. Thirteen patients (Table 1) with lower-extremity amputations secondary to PVD were recruited from a rehabilitation hospital and were subject to the same exclusion criteria as the nonamputee PVD patients (see above).

Screening
To obtain a PVD patient sample with no overt evidence of CVD, all patients were screened and recruited with the close cooperation of the relevant medical staff (ie, vascular surgeons and physiatrists) who were knowledgeable of the exclusion criteria. In all cases, patients and their medical histories were well known to the staff; the medical staff either suggested appropriate potential subjects or verified their appropriateness after the first author had reviewed the subject's history. In some subjects (Table 2), there was a questionable history of previous TIA. In these cases, the subject had been subsequently investigated and judged by their physician on clinical grounds to have had no overt evidence of CVD. Nevertheless, a conservative approach was taken during the hierarchical regression analyses (reported below) by investigating this factor as a potential predictor of cognitive function. In no instance was this questionable TIA history found to be a significant predictor of neuropsychological test performance.

View this table: [in this window] [in a new window]   Table 2. Number (%) of PVD Patients with Vascular Disease Risk Factor

For all PVD patients, the variables diabetes, hypertension, and hyperlipidemia were characterized following standard guidelines.³⁰ Smoking behavior was quantified in terms of pack-years. These factors are summarized in Table 2.

PVD severity was categorized (possible range, 0 to 6) following standard criteria.³⁰ Ten nonamputee patients exhibited ischemic symptoms (mild claudication), placing them in severity category 1; the remaining 6 nonamputees fell into category 2 (moderate claudication). By definition, all amputees fell within category 6 (severe disease, major tissue loss).

CVD Patients
Twenty-nine CVD patients (Table 1) were recruited and selected to match the PVD samples on the basis of age and education. Patients with unilateral atherothrombotic brain infarctions involving the carotid or vertebral-basilar arterial systems were eligible for inclusion. There was a virtually equal number with unilateral involvement of each cerebral hemisphere: 15 patients had right-sided infarcts (10 men), 14 had left-sided infarcts (8 men).

Exclusion criteria included (1) nonatherothrombotic brain infarction (aneurysm, hemorrhage, etc), (2) history of other neurological disorder, (3) history of major psychiatric disorder, (4) history of alcohol and/or drug abuse, or (5) significant medical disease.

Normal Control Subjects
Thirty healthy elderly control subjects (Table 1) were recruited from community centers and selected to match the PVD patient groups on the factors of age and education. Exclusion criteria included (1) evidence of PVD, (2) history of neurological disease, (3) history of major psychiatric disorder, (4) history of alcohol and/or drug abuse (including a heavy [ie, >1 pack per day] current or past habit of cigarette smoking), (5) type I or II diabetes, (6) uncontrolled hypertension, or (7) significant medical disease that might have deleterious effects on cognitive function.

As implied, the PVD, CVD, and control groups did not differ on the factors of age (F[2,85]=1.06, P=.35) or education (F[2,85]=1.49, P=.23).

Procedure and Data Analyses
The procedures followed were in accordance with the ethical standards of Dalhousie University and the healthcare institutions from which patients were recruited. Potential subjects were provided with a short project description, and permission was obtained for a medical chart review and/or brief interview to determine further their eligibility. Appropriate subjects then were invited to participate.

Subjects underwent a comprehensive neuropsychological battery designed to evaluate cognitive function across several domains. Self-report measures of depression (BDI³¹ ) and psychological distress (SCL-90-R³² ) were also administered. The test battery assessed the following six cognitive domains.

(1) Executive function (ie, abstract reasoning, flexibility of thought): Wisconsin Card Sorting Test (WCST³³ ); verbal fluency: Controlled Oral Word Association Test (COWAT³⁴ ; letters [F, A, S] and category [Animals]) and WAIS-R³⁵ Picture Arrangement; WAIS-R Similarities.³⁵

(2) Learning and memory for verbal and nonverbal information: verbal, California Verbal Learning Test³⁶ and Forward and Backward Digit Spans³⁵ ; visual, Rey-Osterrieth Complex Figure delayed recall^{37 38} and Forward and Backward Spatial Spans.³⁹

View larger version (27K): [in this window] [in a new window]   Figure 1. Mean z scores for normal control, PVD, and CVD subjects for each neuropsychological test. *Tests on which PVD differed from control; **tests on which PVDs and CVDs differed from control subjects but not from each other. The number of amputee and nonamputee PVD scores falling in the bottom 5% of normal control scores (z-1.645) is indicated beneath each test. Cat. indicates number of categories; P.Errors, perseverative errors; Concept., conceptual responses; P.Arrngmnt, WAIS-R Picture Arrangement; f/w, forwards; b/w, backwards; Trail, Trail-Making Test; GNT, Graded Naming Test; FAS, verbal fluency, letters; Rey, Rey-Osterrieth Figure; CVLT, California Verbal Learning Test; SDFR, short-delay free recall; and LDFR, long-delay free recall.

(3) Attention/concentration: WAIS-R Digit Symbol Substitution³⁵ ; Forward and Backward Spatial Spans³⁹ ; Forward and Backward Digit Spans³⁵ ; and Trail-Making Test, Parts A and B.⁴⁰

(4) Language: Graded Naming Test⁴¹ ; verbal fluency: COWAT (letters [F, A, S] and category [Animal]).³⁴

(5) Visuospatial/constructional ability: WAIS-R Block Design³⁵ and Rey-Osterrieth Complex Figure copy.^{37 38}

(6) Sensory/motor function: Grooved Pegboard⁴⁰ and Two-Point Discrimination.⁴²

	Results

Top Abstract Introduction Subjects and Methods Results Discussion Appendix 1 References

 
ANOVAs
One-way ANOVAs (Table 3) were computed to determine differences in performance between PVD, CVD, and normal control subjects. The Bonferroni correction was used to control for type I error (significant values of P.002). Tukey A post hoc analyses further elucidated group differences.

View this table: [in this window] [in a new window]   Table 3. Summary of Univariate Fs, Tukey A Tests, and 95% Confidence Intervals for PVD (n=29), CVD (n=29), and Control Subjects (n=30)

PVD patients performed significantly worse (P<.002) than control subjects on eight neuropsychological measures: WCST perseverative errors (P=.0002) and conceptual responses (P=.0003), WAIS-R Picture Arrangement (P<.00009), Rey-Osterrieth Figure delayed recall (P=.0006), Trail Making Part B (P=.0002), WAIS-R Digit Symbol (P=.0001), WAIS-R Block Design (P<.00009), and Rey-Osterrieth Figure copy (P<.00009). For those measures, 95% confidence intervals indicate that the probable true difference in test scores between controls and PVD patients never encompassed the value 0 (Table 3). Moreover, with the exception of performance on the WAIS-R Picture Arrangement and Digit Symbol subtests, the PVD and CVD groups both performed significantly more poorly than controls, but their means did not differ from one another.

To depict the pattern of performance across different neuropsychological measures, individual scores for all three groups were converted to z scores (ie, =0, SD=1), based on the control group test scores (see Figure). Apart from the general difference in the magnitude of negative z scores between the PVD and CVD groups (ie, CVD patients generally had slightly lower scores), the overall similarity between the performance pattern of the two patient groups is very apparent.

Possibly, PVD patients exhibited a heterogeneous pattern of impairment. That is, some patients might have shown impairment on a given test while others did not; however, group means alone would obscure this. To identify such individuals, impaired performance was conservatively defined as a score falling in the bottom 5% of the controls' standardized score distributions (ie, z -1.645). The number of amputee and nonamputee PVD patients showing impaired performance is summarized in the Figure. Although the results are consistent with those from the univariate ANOVAs, additional information was revealed: 24% of scores on the confrontational naming test (Graded Naming Test⁴¹ ) fell below the z-score cutoff, indicating that a considerable number of PVD patients were impaired on this language test, although the mean scores did not reveal this (see "Appendix").

Regression Analyses
Hierarchical multiple regression analyses were computed to identify the medical variables that predicted cognitive impairment in PVD patients. Only those eight neuropsychological tests on which PVD subjects differed from controls were analyzed. Seven factors were used as independent variables and were forced into the equation in the following order: severity of PVD, questionable history of TIA (see "Screening"), history/presence of ischemic heart disease, hypertension, pack-years of smoking, diabetes, and hyperlipidemia. To determine whether the severity of PVD alone could predict neuropsychological performance, this independent variable was forced into the equation during step 1. Entry of the remaining variables was determined according to which was more strongly related to CVD. Those independent variables considered to have stronger associations⁵ were forced into the equation before those more weakly associated. For testing the significance of the regression components, F_i for each independent variable was based on the change in R² (ie, sr²), the multiple R² after all independent variables had been entered, and the residual degrees of freedom for the final step (df=21; see Reference 43⁴³ , pp 111-112).

For WAIS-R Picture Arrangement (sensitive to abstract sequential reasoning) and Rey-Osterrieth Figure recall (a test of visual memory), no independent variable contributed significantly to the regression equations.

For WCST perseverative errors (reflecting executive function and flexibility of thought), PVD severity explained a significant proportion (15%) of the variance in performance (step 1: R²=.15, F(1,27)=4.83; P<.05). Heart disease was also a significant predictor, explaining an additional 14% of the variance (step 3: R²=.32, F_inc(1,25)=4.51; P<.05). No other variable reliably added to the regression equation (values of P>.05).

The results were similar for WCST Conceptual Responses (another measure of executive function). Severity of PVD explained a significant proportion (15%) of test performance variance (step 1: R²=.15, F(1,27)=5.82; P<.05), as did heart disease (14% of the variance; step 3: R²=.34, F_inc(1,25)=5.50; P<.05). Both were significant negative predictors of performance. Again, no other variable reliably added to that regression equation (values of P>.05).

Heart disease explained 29% of the performance variance on Trail-Making Part B (reflecting attention and concentration) and was the only independent variable to contribute significantly to that regression equation (step 3: R²=.30, F_inc(1,25)=10.43; P<.05).

For WAIS-R Digit Symbol subtest performance (a measure of attention, concentration, and psychomotor speed), severity of PVD (step 1: R²=.12, F(1,27)=7.00; P<.05) and the presence/history of heart disease (step 3: R²=.37, F_inc(1,25)=13.40; P<.05) were significant negative predictors of performance, explaining 12% and 22% of the variance, respectively. Hyperlipidemia was a significant positive predictor (step 7: R²=.65, F_inc(1,21)=12.81; P<.05).

For the WAIS-R Block Design (reflecting visuospatial constructional ability), heart disease was the only significant negative predictor of performance and explained 17% of the variance (step 3: R²=.28, F_inc(1,25)=5.71; P<.05).

For the Rey-Osterrieth Figure copy (reflecting visuospatial constructional ability), heart disease (step 3: R²=.32, F_inc(1,25)=8.00; P<.05) and number of smoking pack-years (step 5: R²=.44, F_inc(1,23)=4.30; P<.05) were significant negative predictors of performance, explaining 22% and 12% of the variance, respectively.

Self-Report Affective Measures
Self-report measures of affect (BDI and SCL-90-R) were obtained from the majority of subjects (27 of 30 control, 9 of 13 amputee PVD, all nonamputee PVD, and 16 of 29 CVD subjects). For control and amputee PVD subjects, missing data were due to time constraints. For CVD subjects, missing data were the result of impaired reading ability of patients with left-hemisphere infarcts; 14 of 16 self-report measures obtained were from patients with right-hemisphere damage.

Univariate test results of group differences for the BDI and the SCL-90-R Global Symptom Index (GSI) are presented in Table 4 for control, amputee PVD, nonamputee PVD, and CVD subjects. Mean scores did not differ (P>.05) on the SCL-90-R GSI, indicating no difference among the groups in global psychological distress. Significant group differences were found for the depression measure (BDI; F[3,64]=4.85; P<.05). Post hoc tests revealed higher BDI scores (P<.05) for the amputee PVD (=12.7; ie, mild depression range³¹ ) relative to control (=5.3) and nonamputee PVD (=6.8) subjects. A correlation conducted to determine whether the higher level of reported depression was negatively associated with neuropsychological performance revealed no significant relationship between overall cognitive function (ie, the mean of the standardized neuropsychological measures [z scores] for each PVD patient) and BDI scores (R=-.062, df=23, t=-0.299; P>.05).

View this table: [in this window] [in a new window]   Table 4. Summary of ANOVAs of Affective Measures

	Discussion

Top Abstract Introduction Subjects and Methods Results Discussion Appendix 1 References

 
Relative to age- and education-matched control subjects, PVD patients exhibited neuropsychological impairments that varied largely as a function of the severity of their peripheral atherosclerosis and the presence or absence of ischemic heart disease.

PVD patients exhibited cognitive deficits in the areas of attention and psychomotor speed, executive function, visuospatial ability, and visual memory. No overall impairments in the PVD subjects as a group were found on tests of language ability, verbal memory, or lateralizing tests of sensory-motor functioning. These data are compelling when considered in terms of their potential clinical significance. For certain measures of executive function, attention, and visuospatial ability, the scores of approximately 30% to 50% of the total PVD sample fell in the bottom 5% of the distribution of normal scores, suggesting that impaired performance on these tests was the rule and not the exception.

It was hypothesized that patients with symptomatic PVD suffer from concurrent CVD and would therefore exhibit a pattern of neuropsychological impairment similar to that observed in patients with recognized symptomatic CVD. The Figure illustrates the striking similarity between the two groups in terms of which tests are sensitive to cognitive dysfunction and the pattern of the impairment. In fact, the group performance of the PVD patients did not differ from that of the CVD patients, a group with verified cerebrovascular lesions, on six of the eight neuropsychological measures on which impairment was demonstrated.

Predictors of Cognitive Impairment
The potential influence of increased depression among the patients was considered. The mean BDI score of the PVD amputees fell in the mild depression range, a level of depressive symptomatology far below that which is reported in studies of the neurobehavioral effects of clinical depression (see References 44 and 45^{44 45} ). The BDI did not correlate with the PVD patients' global neuropsychological performance, indicating that these mild depressive symptoms did not influence their cognitive performance.

PVD severity and a history of ischemic heart disease were the only reliable predictors of cognitive dysfunction. Thus, the hypothesis that the severity of PVD (a peripheral manifestation of atherosclerosis) would be a significant predictor of neurocognitive deficits was supported, underscoring the generalized pathological nature of the atherosclerotic process. This implies that patients with the most severe PVD, especially those with amputations, are at greatest risk for suffering cognitive decline.

A history/presence of ischemic heart disease was also a significant negative predictor of neuropsychological performance. Ischemic heart disease is strongly associated with atherosclerosis in cerebral and peripheral arteries^{1 46} and thus may be another marker of the generalized and severe nature of atherosclerotic disease. Ischemic heart disease may also play a causative role in stroke, generally in the form of thromboembolism.⁴⁷ Also, the gradual development of collateral circulation is an important protective mechanism for the brain against cerebral infarction.⁴⁸ Hypotension from reduced cardiac output can render these anastomotic channels ineffective,⁴⁷ thereby functionally removing this protective collateral supply. Possibly, the presence of heart disease in these PVD patients played such a role.

Despite previous reports of mild negative neurobehavioral effects of atherosclerotic risk factors,^{14 15} these factors were not significant predictors in this study after the effects of the clinical manifestations of atherosclerosis (ie, PVD severity, ischemic heart disease) were considered. Thus, the relationship between atherosclerotic risk factors and neuropsychological function may ultimately be mediated through the former's role in the development of cerebral atherosclerosis and the expression of these factors in end-organ change, rather than because of the presence of those pathologies per se.

Implications
Evidence of neuropsychological impairment in PVD patients has several implications. First, PVD patients, especially those with evidence of generalized (eg, ischemic heart disease) and/or severe atherosclerosis (eg, necessitating amputation), who are already showing evidence of neuropsychological compromise may be at risk for potentially more devastating strokes in the future. Many atherosclerotic risk factors are amenable to treatment. While it is likely that PVD patients have already received medical advice to control these factors, raising the spectre of potential stroke possibly could provide further impetus to modify harmful lifestyle habits.

Second, the results have implications for the conclusions of some studies that have evaluated neuropsychological outcome after carotid endarterectomy (eg, References 10 and 12^{10 12} ). These studies used PVD patients as "normal" surgical control patients to account for practice effects, on the assumption that PVD patients had normal cognitive function. However, the present study demonstrated that this assumption probably was not correct, possibly calling into question some conclusions drawn from cerebral revascularization studies using PVD controls. A recent review of cerebral revascularization efficacy indicated mixed results and argued that there was a lack of support for the hypothesis that surgical revascularization procedures produce significant behavioral gains.⁴⁹ The inclusion of PVD patients as controls in previous studies of cerebral revascularization outcome may have contributed to the variability in the findings.

Third, neuropsychological deficits in PVD amputees might present an impediment to prosthetic rehabilitation, resulting in prolonged or unsuccessful rehabilitation. Specific neuropsychological deficits, namely visuospatial, attention, and memory deficits, have been shown to relate to poorer functional outcome at home.⁵⁰ Also, it is possible that neuropsychological assessment of patients receiving rehabilitation services would help to identify those patients in greatest need because of their neuropsychological deficits.

Finally, the question as to whether PVD patients are in the early stages of a vascular dementia should be addressed. In this study, it was not possible to obtain structural information on the brains and cerebral arteries of the PVD patients. However, obtaining this information and relating it to neuropsychological function and rehabilitation/functional outcome represents the next logical avenue of research in this area.

Information regarding the integrity of the brain in PVD patients is scanty. Bots et al⁵¹ examined brain MRIs of 111 community-dwelling elderly people to determine the relationship between cerebral WMLs and atherosclerosis in cerebral, coronary, and peripheral arteries. PVD severity was positively associated with increasing WML probability. The odds ratio of PVD subjects having WMLs (after adjustment for sex and age) was 2.4. No change was observed in the magnitude of association between PVD and WMLs after additional adjustment for cardiovascular disease risk factors, again suggesting that the manifestation of peripheral atherosclerosis is a stronger predictor of pathological brain changes than these risk factors.

Vascular dementia is a syndrome caused by a number of vascular mechanisms and brain mechanisms (eg, total volume of tissue destroyed, infarct location, functional disconnection) rather than a disease entity per se.⁵² Emory and colleagues⁵³ argue that there is a series of pathological processes preceding actual tissue infarction and suggest the term "preinfarct state" to account for cognitive changes in patients with arteriosclerotic diseases in whom cerebral infarcts may or may not be evident. Additional support for the preinfarct concept includes evidence that long-term potentiation in rat hippocampi can be disrupted after 6 months of chronic noninfarctional cerebral hypoperfusion.⁵⁴ These authors speculated that this might represent a category of chronic cerebral ischemia, one in which chronic hypoperfusion leads to impaired neuronal function but without resulting in cerebral infarction.

Although the PVD patients studied here would not, as a group, meet diagnostic criteria for vascular dementia, we speculate about the possibility that, for some, their deficits might represent a vascular dementia in statu nascendi. Given the assumption of the absence of structural brain alteration in these PVD patients, the preinfarct concept could be proposed to account for their neuropsychological deficits. Only longitudinal study that includes structural imaging would verify this. In the meantime, these data indicate that healthcare practitioners should be alert to the possibility of vascular-related cognitive decline in patients with PVD due to chronic atherosclerosis.

	Selected Abbreviations and Acronyms

 

BDI = Beck Depression Inventory CVD = cerebrovascular disease PVD = peripheral vascular disease SCL-90-R = Symptom Check List-90-Revised TIA = transient ischemic attack WAIS-R = Wechsler Adult Intelligence Scale, Revised WML = white matter lesion WSCT = Wisconsin Card Sorting Test

	Acknowledgments

 
This study was conducted in partial fulfillment of the doctoral requirements at Dalhousie University (Dr Phillips) and was supported by a Dalhousie University Graduate Fellowship (Dr Phillips). The authors are grateful to the following for their assistance: members of the Department of Psychology, Dalhousie University, Halifax, Nova Scotia; staff of the Neuropsychology Division, Department of Psychology, Foothills Hospital, Calgary, Alberta; staff of the Nova Scotia Rehabilitation Centre, Halifax, Nova Scotia; staff at the Non-Invasive Vascular Diagnostic Laboratory, Queen Elizabeth II Medical Centre (VGH), Halifax, Nova Scotia; and staff at the Department of Clinical Neurosciences, University of Calgary, Alberta. We also thank the subjects for their participation.

	Footnotes

 
Reprint requests to Dr N.A. Phillips, Department of Psychology, Concordia University, 7141 Sherbrooke St W, Montreal, Quebec, Canada, H4B 1R6.

Portions of these data were presented at the International Neuropsychological Society Meeting, Chicago, Ill, February 14-17, 1996.

	Appendix 1

Top Abstract Introduction Subjects and Methods Results Discussion Appendix 1 References

 
Given the well-documented effects of unilateral cerebrovascular lesions on cognitive function (generally, language-related impairment after left-hemisphere damage and visuospatial deficits after right-hemisphere damage), the possible existence of two such subgroups in the PVD sample was explored. Discriminant function analysis derived from test scores of left- and right-hemisphere damaged CVD patients classified 10 PVD subjects as showing a predominantly "left-hemisphere" pattern of performance and 19 as predominantly "right-hemisphere." ANOVAs indicated that these PVD subgroups differed in the expected direction (ie, "left"<"right") on language-related tests. However, these small sample sizes demand that these observations be interpreted cautiously.

Received November 25, 1996; revision received January 21, 1997; accepted January 21, 1997.

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