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(Stroke. 1996;27:1205-1210.)
© 1996 American Heart Association, Inc.

Articles

Dementia After First Stroke

Bruno Censori, MD; Ornella Manara, MD; Cristina Agostinis, MD; Massimo Camerlingo, MD; Luciano Casto, MD; Bruna Galavotti, MD; Tania Partziguian, MD; Maria Cristina Servalli, MD; Bruno Cesana, MD; Giorgio Belloni, MD Angelo Mamoli, MD

the Neurologia 2 (B. Censori, M.C., L.C., B.G., T.P., M.C.S., A.M.) and the Neuroradiology Service (O.M., C.A., G.B.), Ospedali Riuniti, Bergamo, and the Epidemiologic Laboratory, IRCCS Ospedale Maggiore, Milan (B. Cesana), Italy.

Correspondence to Dr Bruno Censori, Divisione di Neurologia 2, Ospedali Riuniti, L.go Barozzi, 1, 24100 Bergamo, Italy.

	Abstract

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Background and Purpose Cognitive deficits may significantly worsen the quality of life after stroke. Our aim was to determine the frequency of dementia in a consecutive series of previously nondemented patients between the ages of 40 and 79 years at 3 months after a first ischemic stroke.

Methods All patients admitted to our department during an 18-month period who met the above criteria were visited and tested and underwent a CT scan 3 months after their stroke. Dementia was diagnosed according to criteria of the National Institute of Neurological Disorders and Stroke and AIREN, but cases with aphasia were not excluded.

Results Of 304 patients admitted for stroke, 146 were eligible for study. Eleven refused to participate, 25 were dead at 3 months, and 110 were tested. Fifteen patients were demented (13.6%; 95% confidence interval [CI], 7.8% to 21.5%), and six had severe isolated aphasia, neglect, or memory deficit (5.4%). Excluding patients with aphasia, 5.0% of cases showed dementia (95% CI, 1.6% to 11.3%). The frequency of dementia was 24.6% (95% CI, 14.5% to 37.3%), considering only patients with supratentorial lesions and with residual deficits of elementary functions (paresis, sensory deficits) at the time of examination. Demented patients had significantly more diabetes (P=.029), atrial fibrillation (P=.032), aphasia at entry (P<.001), large middle cerebral artery infarctions (P<.001), and a more severe neurological deficit at entry (P=.003) and at 3 months (P<.001). At CT scan, demented patients had a larger mean volume of the recent lesion (P<.001) and more lesions in the frontal lobe (P=.041). An exploratory multivariate analysis selected age between 60 and 69 years (odds ratio [OR], 45.8; 95% CI, 2.9 to 726.0), diabetes (OR, 59.4; 95% CI, 4.3 to 821.0), aphasia (OR, 14.8; 95% CI, 2.0 to 111.0), a large middle cerebral artery infarction (OR, 30.0; 95% CI, 2.7 to 334.0), and lesions of the frontal lobe (OR, 9.8; 95% CI, 1.3 to 72.8) as significant independent correlates of poststroke dementia.

Conclusions Dementia is relatively frequent after a clinical first stroke in persons younger than 80 years, and aphasia is very often associated with poststroke dementia. If aphasic patients are not considered, it may be necessary to screen a very large number of subjects to collect an adequate sample of demented cases.

Key Words: aphasia • dementia • stroke, ischemic • tomography, x-ray computed

	Introduction

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Stroke is a major cause of disability in the elderly.¹ When severe, it affects the quality of life both of its victims and their families and is often a cause of institutionalization of persons previously living autonomously. Cognitive deficits significantly hinder the human relationships between patients and their families or caregivers² ; they reduce the ability to cope with physical impairment and may interfere with rehabilitation programs. Dementia after stroke also seems to be a predictor of reduced survival.^{3 4}

Despite the influence of cognitive status on the poststroke quality of life, only recently have there been systematic efforts to assess global intellectual efficiency after brain infarction.^{5 6 7 8 9} Patients with severe aphasia have usually been excluded from such studies because they cannot be adequately tested.¹⁰ However, this exclusion may lead to the underestimation of the frequency of poststroke dementia.^{11 12}

We report the results of a study on the frequency of dementia after a first ischemic stroke in a consecutive primary hospital-based population aged 40 to 79 years. Patients with severe aphasia were not excluded because we also wanted to determine what fraction of possibly demented cases might be found in this group.

	Subjects and Methods

Top Abstract Introduction Subjects and Methods Results Discussion References

 
We considered all patients with an acute ischemic stroke admitted to our neurology department from April 1, 1993, through September 30, 1994. Our hospital is a primary-care institution, serving a mixed urban and rural area of about 1 million people. Patients with stroke are admitted to our department directly from their homes, or after examination in the emergency department, without further selection. All patients are studied according to the following protocol: clinical history and identification of risk factors for cerebrovascular diseases, neurological examination at entry and daily for the first week, laboratory examinations, electrocardiogram, chest x-ray, color Doppler study of neck vessels, CT scan at entry in most cases, and CT scan between 3 and 8 days after stroke in all cases. The search for vasculitis or altered coagulation states, transthoracic and transesophageal echocardiography, angiography, brain MRI, and SPECT are carried out in selected cases according to clinical indications.

Stroke was defined as focal neurological deficits of acute onset, lasting >24 hours, due to brain ischemia as shown by CT scan or of presumed ischemic nature after appropriate clinical and neuroradiological workup.¹

Exclusion criteria were (1) age <40 or 80 years; (2) resolution of deficits within 24 hours, without corresponding CT lesions; (3) previous clinical stroke defined as history of focal neurological signs of sudden onset, with adequate medical documentation (hospital discharge form, CT scan), or persisting deficits; (4) preexisting dementia, diagnosed through knowledgeable informants on the basis of functional impairment and obvious cognitive deficits (no standardized scale was used); (5) history of alcohol abuse (ie, >600 g/wk); (6) history of retarded psychomotor development, psychosis, or other neurological disease involving the CNS; (7) unusual causes of stroke (ie, vasculitis, dissection); (8) brain ischemia due to cardiorespiratory arrest; (9) systemic diseases known to involve the CNS (ie, lupus erythematosus, AIDS); (10) severe sensory impairment (blindness, deafness); (11) severe depression, diagnosed according to the criteria for major depression of the Diagnostic and Statistical Manual of Mental Disorders, DSM-III-R¹³ ; and (12) cancer discovered in the previous 5 years.

All surviving eligible patients were seen between 3 and 4 months after their stroke for clinical, neuropsychological, and neuroradiological reevaluation. At that date, a neurologist collected the following data: (1) sex; (2) age (categorized as between 40 and 59, between 60 and 69, and between 70 and 79 years), education (categorized as 0 to 8 years versus >8 years); (3) cerebrovascular risk factors, including cigarette smoking (10 cigarettes per day), hypertension (treatment or two or more measurements before stroke of systolic pressure 180 or diastolic pressure 90 mm Hg), diabetes (treatment or fasting blood glucose >7.8 mmol/L before stroke), hypercholesterolemia (total cholesterol >6.2 mmol/L), ischemic heart disease (previous myocardial infarction or angina), and atrial fibrillation; (4) stroke severity at entry, day 7, and at the 3-month visit, scored according to the NIH Stroke Scale¹⁴ ; and (5) presence of aphasia in the acute phase of stroke. The recent stroke was categorized according to its mechanism, following accepted criteria (atherothromboembolic, cardioembolic, lacunar, undetermined),¹⁵ and according to stroke syndrome, following the classification of Bamford et al¹⁶ (TACI [ie, syndrome due to a large infarct in the MCA territory, with or without anterior cerebral artery involvement], PACI, POCI, and LACI).

All patients were tested with a neuropsychological battery including the MMSE,¹⁷ the Token Test, a Naming Test with 10 objects, a Number Cancellation Test used as a measure of sustained attention, Babcock's Story for verbal memory with immediate and delayed recall, Corsi's Blocks for spatial span, and a Test of Drawing Copy for visuospatial functions.¹⁸ With the exception of the MMSE and the Naming Test, results of all the other tests were considered pathological if the score was below the lower limit of sex-, age-, and education-corrected norms for the Italian population as recently published.¹⁹ The Naming Test results were considered pathological if fewer than eight objects were correctly named, since 8 was the lowest score obtained in this test by a sample of neurologically normal subjects of comparable age. The MMSE score was considered pathological if it was 23. The HDRS²⁰ was used to assess the presence of poststroke depression.

Dementia was diagnosed according to NINDS-AIREN criteria¹⁰ when there was clinical evidence of cognitive decline that appeared after the stroke according to the patient's relatives when everyday functioning was affected, memory was impaired, and there were at least two other pathological scores in the test battery. If patients fulfilled the neuropsychological criteria for dementia but their relatives were uncertain whether any cognitive decline antedated the stroke, or they had not noticed significant behavioral changes after the ictus, poststroke dementia was diagnosed, but its relation to stroke was considered uncertain.

For patients with aphasia of sufficient severity to interfere with neuropsychological testing, the patient's relatives were questioned about everyday behavior, initiative, efforts to communicate and to establish interpersonal relationships, and collaboration in tasks related to personal hygiene, dressing, eating, and movements around the house. If the patients were thought to be behaviorally unchanged or showed initiative and routinely attempted to use their residual functions, they were classified as having an SICD and were not counted as demented. Patients with severe isolated memory deficits or marked neglect were also classified as having an SICD.

At the 3-month visit, an unenhanced CT scan of the head was performed by one of two experienced neuroradiologists who were not aware of the neuropsychological diagnosis but knew the probable lesion site. Slice thickness was 5 mm for the posterior fossa and 10 mm for more cranial sections. The following features were evaluated: (1) presence of a recent lesion, consistent with symptoms; (2) volume of the recent lesion, calculated by multiplying lesion area by slice thickness in all CT slices showing the lesion (lesion area was automatically calculated after the lesion contour was outlined with the CT console trackball); (3) presence of old asymptomatic lesions; (4) total volume of all lesions, recent and old, present in the scan; (5) side of the lesion (dominant versus nondominant or vertebrobasilar); (6) main cerebral lobe affected; (7) leukoaraiosis (scored as present or absent); and presence of (8) cortical and (9) subcortical atrophy (scored as present or absent).

All the demographic, clinical, and CT features were compared in patients with poststroke dementia and patients without dementia by means of the ² test or Fisher's exact test for categorical variables and Student's t test for continuous variables assumed to have a normal distribution. Patients with SICD were not considered further for this analysis. Variables with a value of P.10 on univariate analysis were subjected to multivariate analysis with a backward logistic regression procedure to find those independently associated with dementia.

	Results

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Characteristics of the Study Sample
During the study period, 304 patients were admitted to our department because of ischemic stroke. One hundred forty-six met the inclusion criteria (48.0%). Of these, 25 (25193/=17.1%) died within the 3 months following the stroke. Analysis of their clinical features showed that on average they were significantly older (70.8±8.0 versus 65.1±9.3 years; P=.005) and had more severe deficits at entry (P<.001) and a higher frequency of TACIs than stroke survivors (P<.001) (data not shown). Of the 121 survivors, 11 (11193/=7.5%) did not undergo the 3-month evaluation for various reasons, not including severity of deficit or dementia. Five of these 11 patients were interviewed by telephone by one of the investigators (B. Censori), who thought that none was demented; a formal cognitive test was not administered.

The remaining 110 patients (110193/=75.3%) underwent clinical, neuropsychological, and CT scan investigations. There were 71 men and 39 women with a mean±SD age of 65.1±9.5 years and a mean±SD education of 6.6±3.6 years. Aphasia was present in 33 patients (30.0%) at onset of symptoms. Eight patients (7.3%) had an NIH score of 0 at day 7 (ie, normal neurological examination), and 37 (33.6%) had a score of 0 at 3 months. Twenty-six of the latter (70.3%) had a CT lesion consistent with their signs during hospitalization. Seventeen patients (15.4%) had no lesions related to their recent stroke at the 3-month CT scan. No patient had an HDRS score 14.

Eighty-nine patients (80.9%) had no major cognitive deficit. Six patients (5.4%) had an SICD (4 with aphasia, 1 with verbal memory disturbances, and 1 with left neglect). Fifteen patients were demented according to preset criteria (15/110=13.6%; 95% CI, 7.8% to 21.5%); 6 had left hemisphere TACIs (40.0%) with very severe or global aphasia, 2 had right hemisphere TACIs (13.3%), 4 had PACIs (26.7%; all with aphasia), 2 had LACIs (13.3%), and 1 had a POCI (6.7%). The relation of dementia to stroke for the two lacunar cases was considered to be uncertain, according to the definition in "Methods."

Excluding the 10 patients with aphasia left only five cases of dementia (5/100=5.0%; 95% CI, 1.6% to 11.3%). Excluding cases with lesions limited to the brain stem or cerebellum and cases without residual deficits of elementary functions (ie, paresis or sensory deficit), 15 of 61 patients were demented (24.6%; 95% CI, 14.7% to 37.3%) (9.8% considering only nonaphasic cases; 95% CI, 3.3% to 21.4%).

Clinical Features and Univariate Analysis
Mean age was not significantly different between demented and nondemented patients (Table 1); however, the frequency of dementia was significantly higher in the 60- to 69-year age class (10/33; 28.6%) compared with both the 40 to 59 (2/31; 6.4%) and the 70 to 79 (3/38; 7.9%) age classes (P=.017).

View this table: [in this window] [in a new window]   Table 1. Univariate Analysis: Clinical Features

Eight of 16 patients with TACIs had dementia (50.0%) versus 4 of 44 with PACIs (9.1%), 1 of 23 with POCIs (4.3%), and 2 of 21 with LACIs (9.5%) (P<.001). In the TACI group, 6 of 9 with left infarcts were demented (66.7%) as opposed to 2 of 7 with right hemisphere infarcts (28.6%) (P=.155).

There was no significant association between stroke mechanism and dementia, although patients with cardioembolic strokes seemed to become demented with slightly higher frequency (P=.181).

The mean NIH score at entry was 10.9±6.32 for demented patients versus 5.7±4.71 for nondemented cases (P<.001); at 3 months, mean NIH scores were 8.5±6.49 for demented and 1.9±2.66 for nondemented subjects (P<.001). Nine of 15 patients (60.0%) with dementia had an NIH score 8 at 3 months (ie, severe hemiparesis or hemiplegia) versus 5 of 89 patients without dementia (5.6%) (P<.001). After items related to questions, commands, and neglect were excluded, no patient with an NIH score of 0 at 3 months was demented versus 15 of 67 (22.4%) patients with a score 1 (P=.005). Among patients with a neurological score 1 but <8 at 3 months, 6 of 53 had dementia (11.3%) versus 9 of 14 patients with a score 8 (64.3%) (P<.001).

On univariate analysis, in addition to symptom severity, atrial fibrillation, type II diabetes, aphasia at entry, and TACIs were significantly more frequent among demented cases (Table 1). Dominant hemisphere strokes were also more frequent, with the difference falling just short of significance. All the other clinical variables were not significantly different between the two groups.

CT Features and Univariate Analysis
Regarding CT features, demented patients had significantly more lesions in the MCA territory, more frontal lobe lesions, and a larger volume of the recent lesion and of recent and old lesions combined (Table 2). The frequency of old asymptomatic lesions was lower in the demented group, at a borderline significance value (P=.061). No patient without recent lesions or with lesions limited to the infratentorial compartment had dementia. The only demented patient with a vertebrobasilar stroke had a lesion in the left occipital, temporomesial, and thalamic regions.

View this table: [in this window] [in a new window]   Table 2. Univariate Analysis: CT Features

Lesion size among demented cases was very variable, even excluding the two lacunar strokes, ranging from 2.6 to 110.0 cm³. The two demented patients with nonlacunar right hemisphere lesions had lesion volumes of 61.3 and 100.0 cm³; however, among nondemented subjects with right hemisphere syndromes, three had lesion sizes >50 cm³ (53.0, 53.9, and 78.4 cm³, with MMSE scores of 27, 28, and 27, respectively). The size of the recent lesion was 100 cm³ in only two patients; both were demented, one with a left and one with a right MCA stroke. There was no correlation between the MMSE score and size of the recent lesion in nondemented patients (n=89; r=.0068), even excluding cases without recent lesions (n=72; r=.0406) and patients with lesions limited to the brain stem (n=62; r=.0110). The same lack of correlation was seen when considering the total volume of recent and old lesions combined.

Multivariate Analysis
Because of the low absolute number of demented cases, a multivariate analysis was carried out for exploratory purposes only. For this purpose, lesion size was categorized as 20 cm³ versus <20 cm³, syndrome was categorized as TACI versus all others, and lobe was categorized as frontal versus all others. Furthermore, the variable "asymptomatic lesions" was not included, as it did not seem plausible that old lesions should be protective against poststroke dementia. The NIH score at 3 months was also left out, since when it was divided into 8 versus <8, the first category completely overlapped with TACI syndromes. This analysis selected age between 60 and 69 years (OR, 45.8; 95% CI, 2.9 to 726.0), diabetes (OR, 59.4; 95% CI, 4.3 to 821.0), aphasia (OR, 14.8; 95% CI, 2.0 to 111.0), TACIs (OR, 30.0; 95% CI, 2.7 to 334.0), and lesions of the frontal lobe (OR, 9.8; 95% CI, 1.3 to 72.8) as significant independent correlates of poststroke dementia (Table 3).

View this table: [in this window] [in a new window]   Table 3. Multivariate Analysis

	Discussion

Top Abstract Introduction Subjects and Methods Results Discussion References

 
A fairly high percentage of patients become demented after a clinical first stroke. The percentage becomes quite high if the stroke affects supratentorial CNS regions and the impairment of elementary neurological functions is permanent. This cognitive impairment significantly reduces the ability of both the patients and their families or caregivers to cope with poststroke neurological deficits, as reported by those who were interviewed in this respect. Since patients with dementia often had severe sensorimotor impairment, the resultant burden for caregivers was quite high. The degree of dementia, however, did not always parallel that of neurological deficits: it was severe in aphasic patients with large dominant hemisphere strokes, but it was mild in the two patients with left hemiplegia and large right MCA infarcts, who had MMSE scores of 22 and 23.

To evaluate fully the cognitive "cost" of stroke, it should be considered that dementia, as it is usually defined, represents only the most severe extreme of the cognitive consequences of stroke. More restricted impairments involving one or two neuropsychological functions may be even more frequent than dementia^{21 22} and may perhaps subtly affect the patients' cognitive efficiency.

Our figure of poststroke dementia is very similar to that found by Tatemichi et al,⁷ after subtraction of patients with prestroke Alzheimer's disease from the latter series. However, this is probably a coincidence, since the two populations are quite different with respect to age, education, ethnic homogeneity, inclusion of aphasia, and presence of conditions affecting the brain before the index stroke. The specification of these features is critical for the comparison of different studies. We chose to concentrate on those patients who are not very old because they are likely to survive longer after stroke and thus require prolonged assistance if they become unable to care for themselves. Also, as the prevalence of Alzheimer's disease increases with age and is about 10% after 80 years of age,²³ a precise definition of the etiology and timing of cognitive decline observed after stroke in very old people may be quite difficult²⁴ and identification of associated factors less reliable. Unusual causes of stroke were excluded because we wanted a relatively homogeneous group with respect to the etiology of stroke, and recurrent strokes were excluded because large or strategically placed preexisting lesions may confound anatomicoclinical correlations.

Two thirds of our demented cases had aphasia. Such patients are usually excluded from dementia studies because of difficulties in interpreting test results. From the clinical standpoint, there is little doubt that patients with global aphasia from a large MCA infarct are demented. Furthermore, several data sources suggest that intelligence, or cognitive efficiency, relies heavily on the integrity of language processing and the dominant hemisphere. Split-brain studies show that the right hemisphere has a very limited ability to handle abstract concepts and carry out inferences when it is disconnected from the left hemisphere.^{25 26} Also, Basso et al²⁷ showed that aphasia significantly affected different tests of "nonverbal" intelligence in a large population that consisted mostly of patients with a first stroke, ischemic or hemorrhagic. Finally, studies of multi-infarct dementia^{28 29} consistently have found that lesions of the left hemisphere are a strong correlate of intellectual deterioration. Therefore, the exclusion of cases with global aphasia or large lesions of the dominant hemisphere would markedly lower estimates of poststroke dementia.

Only a functional criterion was used to assess the presence of dementia in severely aphasic patients. This method may be criticized as depending on subjective interpretation of the patients' behavior. However, we considered as demented only those aphasic patients showing marked functional impairment that did not seem to be explained by their hemiparesis or communication deficits. This criterion was probably more conservative than that adopted for nonaphasic cases, in which much less functional impairment could be associated with a neuropsychological diagnosis of dementia. Nonetheless, although it did not seem difficult to evaluate the behavior of patients with very severe global aphasia and large MCA infarcts, more subjective interpretation was needed for patients with less severe aphasia (ie, the four PACIs), who were impaired in neuropsychological tests by their language deficits. Therefore, among the latter cases, the percentage classified as demented or SICD will depend in part on the researcher's judgment until a functional scale is validated in large groups of aphasic subjects.

The decision to include cases with symptoms lasting >24 hours but without residual neurological deficits at follow-up (so-called protracted transient ischemic attacks or reversible ischemic neurological deficits³⁰ ) also influenced the dementia figure. We did not reject these cases because (1) it is widely thought that signs lasting more than a few minutes are often accompanied by structural brain damage,^{30 31 32} and (2) multiple cognitive deficits could be a consequence of focal ischemic lesions without associated impairment of elementary neurological functions. In retrospect, it seems that such isolated multiple cognitive deficits are quite rare, if present at all, in a primary hospital-based population of strokes. The high percentage of cases with a mild deficit at admission may suggest that we have caught a representative sample of the spectrum of stroke in the population, since patients with mild deficits are the ones that may not come to the hospital after a first stroke.

The aim of this study was to assess the frequency of diffuse cognitive impairment after a first stroke, not to test the applicability of the recent NINDS-AIREN classification of vascular dementia.¹⁰ However, if only subjects without severe aphasia or a TACI are considered, as prescribed by the latter classification, in the present study very few patients with dementia are found (3/98=3.1%), and only one of them is in the category of dementia due to infarct in a "strategic" location (the patient with mesial temporo-occipital and thalamic infarction). Such a low percentage of demented cases suggests that further studies assessing the prevalence of poststroke dementia and its causative factors may require the screening of a very large number of subjects. Series coming from academic centers or rehabilitation wards may include higher percentages of patients with dementia from lesions of so-called "strategic areas"^{33 34 35 36 37} because of different criteria for hospitalization, but such cases seem to represent a very small part of the general population of first strokes, judging from our data.

Although the results of multivariate analysis must be taken very cautiously because of the small number of cases with dementia and the extremely wide CIs, some considerations can be made about features associated with poststroke dementia. In our series, combined site and size of lesion appear to be the most significant factors influencing cognitive outcome. A large lesion of the dominant hemisphere in the MCA territory almost always led to dementia, and the finding of a TACI on the first day of symptom onset predicted dementia in 50% of those who survived at least 3 months. However, a large lesion did not seem sufficient to cause dementia per se if it affected the nondominant hemisphere, at least for lesion sizes <100 cm³. Thus, a "mass action" concept alone cannot explain the appearance of dementia after stroke. This conclusion is also supported by our failure to find a relationship between MMSE scores and lesion size in nondemented patients. It will be interesting to see whether lesion size influences the probability of developing dementia in the years that follow the index stroke.

Our CT findings cannot be directly compared with those obtained in studies of chronic vascular, or multi-infarct, dementia, in which multiple small, deep infarcts, leukoaraiosis, and cortical and subcortical atrophy characterize the picture.^{5 29 38 39 40} In our series, none of the latter features was significantly associated with poststroke dementia, although some comparisons were limited by the small size of the demented group. In fact, asymptomatic CT lesions were much less frequent in the demented group, with the difference falling just short of significance. Perhaps this is due to the fact that demented patients usually had very large symptomatic lesions that obscured small, preexisting, ipsilateral, and cortical or subcortical hypodensities. Altogether, however, our CT data clearly indicate that acute focal damage is more important than the underlying brain status in causing poststroke dementia in previously nondemented subjects.

The lack of a clear association between increasing age and dementia (for patients younger than 80 years) is in accordance with the results of other studies.^{8 33} However, the exclusion of dead subjects may have biased the results, since the patients who died were on average much older and often had very large lesions in the MCA territory. Thus, it is possible that many of them would have been found to be demented if they had survived long enough to be tested. This consideration may perhaps explain the association between dementia and age between 60 and 69 years seen on multivariate analysis.

In accordance with Tatemichi et al,³³ we found that diabetes was significantly associated with poststroke dementia. Katzman et al⁴¹ also found that diabetes was a significant predictor of the development of vascular dementia in a nondemented elderly population. However, Woo et al⁴² could not find any relationship between a history of diabetes, newly diagnosed diabetes, or admission hyperglycemia and mental status 3 months after stroke. Perhaps diabetes causes small-vessel disease⁴³ that impairs the recovery from acute ischemic damage, or hyperglycemia in the acute phase of stroke aggravates cellular damage through tissue acidosis.^{44 45} The relevance of the latter mechanism for clinical practice, however, is not firmly established yet.^{42 46}

The percentage of lacunar cases with dementia was similar to that found in other studies.^{47 48 49} For both of our patients, it was not possible to relate clearly the cognitive impairment to the recent stroke. Such cases could be examples of chronic cerebrovascular disease, evidenced by the index stroke, and perhaps deserve separate consideration for descriptive and therapeutic purposes.

Finally, we cannot exclude that some of our patients with poststroke dementia had subclinical Alzheimer's disease, which was simply detected by neuropsychological tests or amplified the cognitive effects of the recent stroke. However, the low frequency of dementia in the oldest age group and the quite homogeneous features of demented patients (dominant hemisphere infarcts, large lesions of the frontal lobes) do not indicate the presence of an occult chronic dementing process. Only a pathological study can provide diagnostic certainty in this respect.

In conclusion, our data show that dementia is a relatively frequent sequela of first ischemic strokes, especially when supratentorial CNS areas are affected and the impairment of elementary neurological functions is permanent. Cerebrovascular risk factors and side, site, and size of lesion seem to interact in producing significant cognitive compromise after stroke. Our observations may not be generally applicable to patients with recurrent strokes or older than 80 years.

	Selected Abbreviations and Acronyms

 

AIREN = Association Internationale pour la Recherche et l'Enseignement en Neurologie CI = confidence interval CNS = central nervous system HDRS = Hamilton Depression Rating Scale LACI = lacunar infarct MCA = middle cerebral artery MMSE = Mini-Mental State Examination NIH = National Institutes of Health OR = odds ratio PACI = partial anterior circulation infarct POCI = posterior circulation infarct SICD = severe isolated cognitive deficit TACI = total anterior circulation infarct

	Acknowledgments

 
We gratefully acknowledge the work of Elena Ruggeri, who administered all neuropsychological tests.

Received November 14, 1995; revision received March 18, 1996; accepted March 18, 1996.

	References

Top Abstract Introduction Subjects and Methods Results Discussion References

 

1. World Health Organization Task Force on Stroke and Other Cerebrovascular Disorders. Stroke-1989: recommendations on stroke prevention, diagnosis, and therapy. Stroke. 1989;20:1407-1431.[Free Full Text]
2. Anderson CS, Linto J, Stewart-Wynne EG. A population-based assessment of the impact and burden of caregiving for long-term stroke survivors. Stroke. 1995;26:843-849.[Abstract/Free Full Text]
3. Tatemichi TK, Paik M, Bagiella M, Desmond DW, Pirro M, Hanzawa LK. Dementia after stroke is a predictor of long-term survival. Stroke. 1994;25:1915-1919.[Abstract]
4. Woo J, Kay R, Yuen YK, Nicholls MG. Factors influencing long-term survival and disability among three-month stroke survivors. Neuroepidemiology. 1992;11:143-150.[Medline] [Order article via Infotrieve]
5. Ladurner G, Iliff LD, Lechner H. Clinical factors associated with dementia in ischaemic stroke. J Neurol Neurosurg Psychiatry. 1982;45:97-101.[Abstract]
6. Kotila M, Waltimo O, Niemi M-L, Laaksonen L. Dementia after stroke. Eur Neurol. 1986;25:134-140.[Medline] [Order article via Infotrieve]
7. Tatemichi TK, Desmond DW, Mayeux R, Paik M, Stern Y, Sano M, Remien RH, Williams JBW, Mohr JP, Hauser WA, Figueroa M. Dementia after stroke: baseline frequency, risks, and clinical features in a hospitalized cohort. Neurology. 1992;42:1185-1193.[Abstract/Free Full Text]
8. Schmidt R, Mechtler R, Kinkel PR, Fazekas F, Kinkel WR, Freidl W. Cognitive impairment after acute supratentorial stroke: a 6-month follow-up clinical and computed tomographic study. Eur Arch Psychiatry Clin Neurosci. 1993;243:11-15.[Medline] [Order article via Infotrieve]
9. Aronovich BD, Treves TA, Bornestein NM, Korczyn AD. Incidence of dementia after first stroke: 3-year follow-up. Cerebrovasc Dis. 1994;4:238. Abstract.
10. Roman GC, Tatemichi TK, Erkinjuntti T, Cummings JL, Masdeu JC, Garcia JH, Amaducci L, Orgogozo JM, Brun A, Hofman A, Moody MD, O'Brien MD, Yamaguchi T, Grafman J, Drayer BP, Bennett DA, Fisher M, Ogata J, Kokmen E, Bermejo F, Wolf PA, Gorelick PB, Bick KL, Pajeau AK, Bell MA, DeCarli C, Culebras A, Korczyn AD, Bogousslavsky J, Hartmann A, Scheinberg P. Vascular dementia: diagnostic criteria for research studies. Neurology. 1993;43:250-260.[Abstract/Free Full Text]
11. O'Brien MD. Vascular dementia is underdiagnosed. Arch Neurol. 1988;45:797-798.[Medline] [Order article via Infotrieve]
12. Drachman DA. New criteria for the diagnosis of vascular dementia: do we know enough yet? Neurology. 1993;43:243-245.[Free Full Text]
13. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, DSM-III-R. 3rd rev ed. Washington, DC: American Psychiatric Association; 1987.
14. Brott T, Adams HP, Olinger CP, Marler JR, Barsan WG, Biller J, Spilker J, Holleran R, Eberle R, Hertzberg V, Rorick M, Moomaw CJ, Walker M. Measurements of acute cerebral infarction: a clinical examination scale. Stroke. 1989;20:864-870.[Abstract/Free Full Text]
15. Whisnant JP, Basford JR, Bernstein EF, Cooper ES, Dyken ML, Easton JD, Little JR, Marler JR, Millikan CH, Petito CK, Price TR, Raichle ME, Robertson JT, Thiele B, Walker MD, Zimmerman RA. Classification of cerebrovascular diseases III. Stroke. 1990;21:637-676.[Free Full Text]
16. Bamford J, Sandercock P, Dennis M, Burn J, Warlow C. Classification and natural history of clinically identifiable subtypes of cerebral infarction. Lancet. 1991;337:1521-1526.[Medline] [Order article via Infotrieve]
17. Folstein MF, Folstein SE, McHugh PR. Mini-mental state. J Psychiatr Res. 1975;12:189-198.[Medline] [Order article via Infotrieve]
18. Lezak MD. Neuropsychological Assessment. 2nd ed. New York, NY: Oxford University Press; 1983.
19. Spinnler H, Tognoni G, eds. Standardizzazione e taratura italiana di tests neuropsicologici. Ital J Neurol Sci. 1987;6(suppl 8).
20. Williams JBW. A structured interview guide for the Hamilton Depression Rating Scale. Arch Gen Psychiatry. 1988;45:742-747.[Abstract]
21. Desmond DW, Tatemichi TK, Stern Y, Sano M. Cognitive dysfunction following first stroke. Neurology. 1992;42(suppl 3):426.
22. Tatemichi TK, Desmond DW, Stern Y, Paik M, Sano M, Bagiella E. Cognitive impairment after stroke: frequency, patterns, and relationship to functional abilities. J Neurol Neurosurg Psychiatry. 1994;57:202-207.[Abstract]
23. Rocca WA, Hofman A, Brayne C, Breteler MMB, Clarke M, Copeland JRM, Dartigues JF, Engedal K, Hagnell O, Heeren TJ, Jonker C, Lindesay J, Lobo A, Mann AH, Molsa PK, Morgan K, O'Connor DW, da Silva Droux A, Sulkava R, Kay DWK, Amaducci L, for the EURODEM-Prevalence Research Group. Frequency and distribution of Alzheimer's disease in Europe: a collaborative study of 1980-1990 prevalence findings. Ann Neurol. 1991;30:381-390.[Medline] [Order article via Infotrieve]
24. Tomlinson BE, Blessed G, Roth M. Observations on the brains of demented old people. J Neurol Sci. 1968;11:205-242.
25. Gazzaniga MS, Smylie CS. Dissociation of language and cognition: a psychological profile of two disconnected right hemispheres. Brain. 1984;107:145-153.[Abstract/Free Full Text]
26. Gazzaniga MS. Some contributions of split-brain studies to the study of human cognition. In: Reeves AG, ed. Epilepsy and the Corpus Callosum. New York, NY: Plenum Press; 1985:341-348.
27. Basso A, Capitani E, Luzzatti C, Spinnler H. Intelligence and left hemisphere disease. The role of aphasia, apraxia and size of lesion. Brain. 1981;104:721-734.[Free Full Text]
28. Liu CK, Miller BL, Cummings JL, Mehringer CM, Goldberg MA, Howng SL, Benson FD. A quantitative MRI study of vascular dementia. Neurology. 1992;42:138-143.[Abstract/Free Full Text]
29. Gorelick PB, Chatterjee A, Patel D, Flowerdew J, Dollear W, Taber J, Harris Y. Cranial computed tomographic observations in multi-infarct dementia. Stroke. 1992;23:804-811.[Abstract/Free Full Text]
30. Calandre L, Gomara S, Bermejo F, Millan JM, del Pozo G. Clinical-CT correlations in TIA, RIND, and strokes with minimum residuum. Stroke. 1984;15:663-666.[Abstract/Free Full Text]
31. Levy DE. How transient are transient ischemic attacks? Neurology. 1988;38:674-677.[Abstract/Free Full Text]
32. Scheinberg P. Transient ischemic attacks: an update. J Neurol Sci. 1991;101:133-140.[Medline] [Order article via Infotrieve]
33. Tatemichi TK, Desmond DW, Paik M, Figueroa M, Gropen TI, Stern Y, Sano M, Remien R, Williams JBW, Mohr JP, Mayeux R. Clinical determinants of dementia related to stroke. Ann Neurol. 1993;33:568-575.[Medline] [Order article via Infotrieve]
34. Caplan LR, Schmahmann JD, Kase CS, Feldmann E, Baquis G, Greenberg JP, Gorelick PB, Helgason C, Hier DB. Caudate infarcts. Arch Neurol. 1990;47:133-143.[Abstract]
35. Katz DI, Alexander MP, Mandell AM. Dementia following strokes in the mesencephalon and diencephalon. Arch Neurol. 1987;44:1127-1133.[Abstract]
36. Bogousslavsky J, Regli F, Uske A. Thalamic infarcts: clinical syndromes, etiology, and prognosis. Neurology. 1988;38:837-848.[Abstract/Free Full Text]
37. De Renzi E, Zambolin A, Crisi G. The pattern of neuropsychological impairment associated with left posterior cerebral artery infarcts. Brain. 1987;110:1099-1116.[Abstract/Free Full Text]
38. Ishii N, Nishihara Y, Imamura T. Why do frontal lobe symptoms predominate in vascular dementia with lacunes? Neurology. 1986;36:340-345.[Abstract/Free Full Text]
39. Loeb C, Gandolfo C, Bino G. Intellectual impairment and cerebral lesions in multiple cerebral infarcts. Stroke. 1988;19:560-565.[Abstract/Free Full Text]
40. Meyer JS, McClintic KL, Rogers RL, Sims P, Mortel KF. Aetiological considerations and risk factors for multi-infarct dementia. J Neurol Neurosurg Psychiatry. 1988;51:1489-1497.[Abstract]
41. Katzman R, Aronson M, Fuld P, Kawas C, Brown T, Morgenstern H, Frishman W, Gidez L, Eder H, Ooi WL. Development of dementing illnesses in an 80-year-old volunteer cohort. Ann Neurol. 1989;25:317-324.[Medline] [Order article via Infotrieve]
42. Woo J, Lam CWK, Kay R, Wong AHY, Teoh R, Nicholls MG. The influence of hyperglycemia and diabetes mellitus on immediate and 3-month morbidity and mortality after acute stroke. Arch Neurol. 1990;47:1174-1177.[Abstract]
43. Mast H, Thompson JLP, Lee S-H, Mohr JP, Sacco RL. Hypertension and diabetes mellitus as determinants of multiple lacunar infarcts. Stroke. 1995;26:30-33.[Abstract/Free Full Text]
44. Pulsinelli WA, Waldman S, Rawlinson D, Plum F. Moderate hyperglycemia augments ischemic brain damage: a neuropathologic study in the rat. Neurology. 1982;32:1239-1246.[Abstract/Free Full Text]
45. Oppenheimer SM, Hoffbrand BI, Oswald GA, Yudkin JS. Diabetes mellitus and early mortality from stroke. Br Med J. 1985;291:1014-1015.
46. Woo E, Chan YW, Yu YL, Huang CY. Admission glucose level in relation to mortality and morbidity outcome in 252 stroke patients. Stroke. 1988;19:185-191.[Abstract/Free Full Text]
47. Tatemichi TK, Foulkes MA, Mohr JP, Hewitt JR, Hier DB, Price TP, Wolf PA. Dementia in stroke survivors in the Stroke Data Bank cohort. Stroke. 1990;21:858-866.[Abstract/Free Full Text]
48. Miyao S, Takano A, Teramoto J, Takahashi A. Leukoaraiosis in relation to prognosis for patients with lacunar infarction. Stroke. 1992;23:1424-1438.
49. Guerreiro M, Salgado AV, Reis A, Ferro JM. Neuropsychological study of a cohort of lacunar infarctions. Cerebrovasc Dis. 1994;4:224. Abstract.

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