David W. Desmond

Dementia after stroke Baseline frequency, risks, and clinical features in a hospitalized cohort

We determined the frequency of dementia in a cohort of 251 patients aged ⩾60 years hospitalized with acute ischemie stroke, based on examinations performed 3 months after stroke onset. Using modified DSM-III-R criteria, we found dementia in 66 patients (26.3%). Diagnostic agreement among raters was excellent (kappa = 0.96). In a control sample of 249 stroke-free subjects recruited from the community and matched by age, we found dementia in eight subjects (3.2%). Using a logistic regression model to estimate the risk of dementia associated with stroke in the combined samples, the odds ratio (OR) for stroke patients compared with control subjects was 9.4 (p <0.001). Advancing age and fewer years of education were significant, independent correlates of dementia, with a trend evident for race (non-white versus white). Confining the analysis to subjects residing in the Washington Heights-Inwood community of northern Manhattan, the OR was 10.3 (p <0.001) with significant age and race effects. We conclude that ischemie stroke significantly increases the risk of dementia, with independent contributions by age, education, and race.

Risk of dementia after stroke in a hospitalized cohort: Results of a longitudinal study

Stroke is considered the second most common cause of dementia, but the magnitude of the risk posed by stroke has not been fully clarified. The aim of this study was to determine the long-term risk of developing dementia after stroke onset in a hospitalized cohort. We prospectively examined 185 nondemented patients aged ≥60 years hospitalized with ischemic stroke and 241 age-matched nondemented controls without stroke from the same community using neurologic, neuropsychological, and functional assessments given annually. Using criteria modified from the DSM-III-R, we diagnosed incident dementia based on the annual examination findings. We used life-table methods to estimate incidence in the two groups, Kaplan-Meier analysis to determine the proportion surviving without dementia, and Cox proportional-hazards analysis to compute the relative risk (RR) of dementia after 1 to 4 years of follow-up. The incidence of dementia was 8.4 per 100 person-years in the stroke group and 1.3 per 100 person-years in the control group. After 52 months of follow-up, the cumulative proportion (±SE) surviving without dementia was 66.3 ± 5.5% for stroke and 90.3 ± 4.3% for control subjects. The RR of dementia associated with stroke compared with controls was 5.5 (95% CI, 2.5 to 11.1) after adjusting for demographic factors. Older age at stroke onset and fewer years of education were significant covariates, but sex and race were not. A low score on the Mini-Mental State Examination at baseline was a significant predictor when added to this model. We conclude that ischemic stroke in elderly persons increases the long-term risk of developing dementia by approximately five-fold compared with those without stroke. Age, education, and baseline intellectual function contribute independently to that risk.

Frequency and clinical determinants of dementia after ischemic stroke

Objective: To investigate the frequency and clinical determinants of dementia after ischemic stroke. Methods: The authors administered neurologic, neuropsychological, and functional assessments to 453 patients (age 72.0 ± 8.3 years) 3 months after ischemic stroke. They diagnosed dementia using modified Diagnostic and Statistical Manual of Mental Disorders, 3rd ed., revised criteria requiring deficits in memory and two or more additional cognitive domains as well as functional impairment. Results: The authors diagnosed dementia in 119 of the 453 patients (26.3%). Regarding dementia subtypes, 68 of the 119 patients (57.1%) were diagnosed with vascular dementia, 46 patients (38.7%) were diagnosed with AD with concomitant stroke, and 5 patients (4.2%) had dementia for other reasons. Logistic regression suggested that dementia was associated with a major hemispheral stroke syndrome (OR 3.0), left hemisphere (OR 2.1) and right hemisphere (OR 1.8) infarct locations versus brainstem/cerebellar locations, infarcts in the pooled anterior and posterior cerebral artery territories versus infarcts in other vascular territories (OR 1.7), diabetes mellitus (OR 1.8), prior stroke (OR 1.7), age 80 years or older (OR 12.7) and 70 to 79 years (OR 3.9) versus 60 to 69 years, 8 or fewer years of education (OR 4.1) and 9 to 12 years of education (OR 3.0) versus 13 or more years of education, black race (OR 2.6) and Hispanic ethnicity (OR 3.1) versus white race, and northern Manhattan residence (OR 1.6). Conclusions: Dementia is frequent after ischemic stroke, occurring in one-fourth of the elderly patients in the authors’ cohort. The clinical determinants of dementia include the location and severity of the presenting stroke, vascular risk factors such as diabetes mellitus and prior stroke, and host characteristics such as older age, fewer years of education, and nonwhite race/ethnicity. The results also suggest that concomitant AD plays an etiologic role in approximately one-third of cases of dementia after stroke.

Confusion and memory loss from capsular genu infarction A thalamocortical disconnection syndrome

We examined six patients with an abrupt change in behavior after infarction involving the inferior genu of the internal capsule. The acute syndrome featured fluctuating alertness, inattention, memory loss, apathy, abulia, and psychomotor retardation, suggesting frontal lobe dysfunction. Contralateral hemiparesis and dysarthria were generally mild, except when the infarct extended into the posterior limb. Neuropsychological testing in five patients with left-sided infarcts revealed severe verbal memory loss. Additional cognitive deficits consistent with dementia occurred in four patients. A right-sided infarct caused transient impairment in visuospatial memory. Functional brain imaging in three patients showed a focal reduction in hemispheric perfusion most prominent in the ipsilateral inferior and medial frontal cortex. We infer that the capsular genu infarct interrupted the inferior and anterior thalamic peduncles, resulting in functional deactivation of the ipsilateral frontal cortex. These observations suggest that one mechanism for cognitive deterioration from a lacunar infarct is thalamocortical disconnection of white-matter tracts, in some instances leading to strategic-infarct dementia.

Incidence of Dementia After Ischemic Stroke Results of a Longitudinal Study

Background and Purpose— A number of cross-sectional epidemiological studies have reported that one fourth of elderly patients meet criteria for dementia 3 months after ischemic stroke, but few longitudinal studies of the incidence of dementia after stroke have been performed. We conducted the present study to investigate the incidence and clinical predictors of dementia after ischemic stroke. Methods— We administered neurological, neuropsychological, and functional assessments annually to 334 ischemic stroke patients (age, 70.4±7.5 years) and 241 stroke-free control subjects (age, 70.6±6.5 years), all of whom were nondemented in baseline examinations. We diagnosed incident dementia using modified Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition criteria requiring deficits in memory and ≥2 additional cognitive domains, as well as functional impairment. Results— The crude incidence rate of dementia was 8.49 cases per 100 person-years in the stroke cohort and 1.37 cases per 100 person-years in the control cohort. A Cox proportional-hazards analysis found that the relative risk (RR) of incident dementia associated with stroke was 3.83 (95% CI, 2.14 to 6.84), adjusting for demographic variables and baseline Mini-Mental State Examination score. Within the stroke cohort, intercurrent medical illnesses associated with cerebral hypoxia or ischemia were independently related to incident dementia (RR, 4.40; 95% CI, 2.20 to 8.85), adjusting for recurrent stroke, demographic variables, and baseline Mini-Mental State Examination score. Conclusions— The risk of incident dementia is high among patients with ischemic stroke, particularly in association with intercurrent medical illnesses that might cause cerebral hypoxia or ischemia, suggesting that cerebral hypoperfusion may serve as a basis for some cases of dementia after stroke.

The neuropsychology of vascular cognitive impairment: is there a specific cognitive deficit?

The concept of Vascular Cognitive Impairment (VCI) encompasses patients across the entire continuum of cognitive impairment resulting from cerebrovascular disease (CVD), ranging from high-risk patients with no frank cognitive deficit (the brain-at-risk stage) through vascular dementia (VaD). There are accepted differences in the neuropsychological profile of patients with Alzheimers disease (AD) and VaD. In patients with VaD, executive functions that tend to be disproportionately impaired include planning and sequencing, speed of mental processing, performance on unstructured tasks, and attention. Language production may be impaired in patients with VaD but primary language functions otherwise tend to be preserved. Patients with VaD also exhibit significantly more perseverations than patients with AD. Memory impairment is typically evident in patients with AD+CVD but memory impairment may also occur as a primary consequence of stroke in the posterior cerebral artery territory with involvement of the medial temporal lobe, or as a secondary consequence of a cognitive syndrome involving inattention due to primary executive dysfunction. Compared to VaD, patients with AD may exhibit greater deficits in functions (including memory) mediated by posterior cortical structures, such as the temporal and parietal lobes. AD patients exhibit a faster rate of information decay, reduced ability to benefit from cues to facilitate retrieval, and higher frequency of intrusion errors; in addition, certain aspects of language function, such as naming, may exacerbate deficits on verbal memory tasks. AD tends to affect lexicon while VaD tends to affect syntax. When patients with AD exhibit perseverations, they tend to be elicited by tests of semantic knowledge.

Cognition and white matter lesions.

Although it is recognized that ischemic stroke is a potent risk factor for vascular dementia, the influence of white matter lesions (WML) on cognitive function is less clear. In community-based MRI studies that have administered mental status tests to subjects who were free of clinically evident neurologic disease, a weak relationship between WML and generalized cognitive function has been reported. In studies that have administered neuropsychological test batteries, a stronger and more specific association has been recognized between WML and deficits in executive function, most likely due to the involvement of frontal-subcortical pathways. Cognitive deficits may be related to the total volume of the WML, with a threshold perhaps needing to be surpassed before such deficits are evident, but it is likely that the location of the WML also plays a role, with that threshold varying in association with the distribution of the lesions. Potential confounders of the results of previous studies include small, strategically located subcortical infarctions that may be masked by more extensive WML and other comorbid neurologic disorders, particularly Alzheimer’s disease. Future studies should be prospective, utilize standardized methods for structural and functional brain imaging, and administer comprehensive neuropsychological assessments in order to more rigorously investigate the relationship between evolving WML and declining cognitive functions.

Dementia after stroke increases the risk of long‐term stroke recurrence

Background Although risk factors for first stroke have been identified, the predictors of long-term stroke recurrence are less well understood. We performed the present study to determine whether dementia diagnosed three months after stroke onset is an independent risk factor for long-term stroke recurrence. Methods We examined 242 patients (age = 72.0 ± 8.7 years) hospitalized with acute ischemic stroke who had survived the first three months without recurrence and followed them to identify predictors of long-term stroke recurrence. We diagnosed dementia three months after stroke using modified DSM-III-R criteria based on neuropsychological and functional assessments. The effects of conventional stroke risk factors and dementia status on survival free of recurrence were estimated using Kaplan-Meier analyses, and the relative risks (RR) of recurrence were calculated using Cox proportional hazards models. Results Dementia (RR = 2.71, 95% CI = 1.36 to 5.42); cardiac disease (RR = 2.18, CI = 1.15 to 4.12); and sex, with women at higher risk (RR = 2.03, CI = 1.01 to 4.10), were significant independent predictors of recurrence, while education (RR = 1.90, CI = 0.77 to 4.68), admission systolic blood pressure >160 mm Hg (RR = 1.80, CI = 0.94 to 3.44) and alcohol intake exceeding 160 grams per week (RR = 1.86, CI = 0.79 to 4.38) were weakly related. Conclusions Our results suggest that dementia significantly increases the risk of long-term stroke recurrence, with additional independent contributions by cardiac disease and sex. Cognitive impairment may be a surrogate marker for multiple vascular risk factors and larger infarct volume that may serve to increase the risk of recurrence. Alternatively, less aggressive medical management of stroke patients with cognitive impairment or noncompliance of such patients with medical therapy may be bases for an increased rate of stroke recurrence.

Mortality in patients with dementia after ischemic stroke

Objective Although dementia is typically considered to be a consequence of a variety of neurologic diseases, it can also serve as a risk factor for other adverse outcomes. The authors investigated dementia as a predictor of long-term survival among patients with ischemic stroke. MethodsNeurologic, neuropsychological, and functional assessments were administered to 453 patients (mean age ± SD, 72.0 ± 8.3 years) 3 months after ischemic stroke. The authors diagnosed dementia in 119 (26.3%) of the patients using modified Diagnostic and Statistical Manual of Mental Disorders, Revised 3rd Edition, criteria requiring deficits in memory and two or more additional cognitive domains as well as functional impairment. Dementia as a predictor of long-term survival during up to 10 years of follow-up was then investigated. ResultsThe mortality rate was 15.90 deaths per 100 person-years among patients with dementia and 5.37 deaths per 100 person-years among nondemented patients. A Cox proportional hazards analysis found that the relative risk (RR) of death was increased in association with dementia (RR = 2.4; 95% CI = 1.6 to 3.4), adjusting for the following: a major hemispheral stroke syndrome (RR = 1.4); a middle cerebral artery territory index stroke (RR = 1.7); a Stroke Severity Scale score of ≥4, representing more severe stroke (RR = 1.8); atrial fibrillation (RR = 1.8); congestive heart failure (RR = 2.2); recurrent stroke occurring during follow-up (RR = 3.9); and demographic variables. The risk of death increased in association with the severity of dementia, but it did not differ by dementia subtype. ConclusionsDementia is a significant independent risk factor for reduced survival after ischemic stroke, adjusting for other recognized predictors of mortality. The authors hypothesize that patients with dementia are at an elevated risk of mortality because of their increased burden of cerebrovascular disease, a tendency toward undertreatment for stroke prophylaxis among clinicians, or patient noncompliance with treatment regimens.

Ischemic stroke and depression.

Previous studies of depression after stroke have reported widely variable findings, possibly due to differences between studies in patient characteristics and methods for the assessment of depression, small sample sizes, and the failure to examine stroke-free reference groups to determine the base rate of depression in the general population. In an effort to address certain of those methodologic issues and further investigate the frequency and clinical determinants of depression after stroke, we administered the Structured Interview Guide for the Hamilton Depression Rating Scale (SIGH–D) and neurological, neuropsychological, and functional assessments to 421 patients (age = 71.5 ± 8.0 years) 3 months after ischemic stroke and 249 stroke-free control subjects (age = 70.8 ± 6.7 years). We required a SIGH–D total score > 11 for the identification of depression. We found that depression was less frequent (47/421 patients, or 11.2%, and 13/249 control subjects, or 5.2%), less severe, and less persistent in our stroke cohort than previously reported, possibly due to the underrepresentation of patients with a premorbid history of affective illness. Depression was associated with more severe stroke, particularly in vascular territories that supply limbic structures; dementia; and female sex. SIGH–D item analyses suggested that a reliance on nonsomatic rather than somatic symptoms would result in the most accurate diagnoses of depression after ischemic stroke. (JINS, 2003, 9, 429–439.)