The effect of patient attrition on estimates of the frequency of dementia following stroke.

BACKGROUND: Given that prevalence surveys may underestimate the magnitude of the association between an exposure and a disease with high morbidity or mortality, we investigated the effects of patient attrition on estimates of the frequency of dementia following ischemic stroke. PATIENTS AND METHODS: We examined 251 patients 3 months after stroke and diagnosed dementia in 66 (26.3%) based on the results of neuropsychological and functional assessments and modified criteria from the Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised. Those 251 patients were drawn from a larger cohort of 297 patients, with the majority of the remaining 46 patients being unavailable for assessment due to death, severe stroke, or comorbid medical disorders. Using the coefficients in a logistic model of the clinical determinants of dementia based on the 251 patients who were examined, we calculated the probability of dementia for each of the 46 patients who were not examined. We considered a patient to have dementia when that probability was higher than the mean of the median probabilities of dementia in the groups of patients with and without dementia who completed the examinations. RESULTS: The sensitivity and specificity of our diagnostic method were 75.8% and 72.4%, respectively. We recognized dementia in 21 (45.7%) of the 46 unavailable patients, a significantly higher frequency than among examined patients. Additional analyses determined that the factors that increased the risk of becoming unavailable for follow-up, which included more severe stroke, left and right hemisphere infarct locations, and a history of prior stroke, are similar to the factors that increase the risk of dementia after stroke. CONCLUSION: Our findings suggest that dementia is differentially associated with early patient attrition, potentially resulting in the underestimation of its frequency and underrecognition of its importance as an outcome of ischemic stroke.

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.

CADASIL in a North American family: clinical, pathologic, and radiologic findings.

OBJECTIVE: To expand the reported phenotypic range of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). BACKGROUND: Despite numerous patient reports, our knowledge of the phenotypic range of CADASIL remains incomplete. METHOD: We performed clinical, pathologic, and radiologic examinations on members of a family with CADASIL. RESULTS: The proband is a 61-year-old man with a history of migraine and depression who has experienced multiple subcortical infarctions resulting in a stepwise decline. Neuropsychological testing documented a dementia syndrome with frontal lobe features and neurologic examination noted a left hemiparesis and a right-sided palmomental reflex. Brain biopsy with light microscopy revealed a nonatherosclerotic small-vessel angiopathy with periodic acid-Schiff positive granular changes in the media and white matter gliosis, with unremarkable cortex. Genetic testing confirmed a Notch3 mutation. The proband's first cousin has a history of depression, one seizure possibly resulting from an acute stroke, and a learning disorder. Neuropsychological testing demonstrated deficits in executive function and neurologic examination noted persistent extraneous adventitial movements, poor coordination, and primitive reflexes. Skin biopsy with electron microscopy demonstrated granular osmiophilic material within the basement membrane of vascular smooth muscle cells, which is considered to be pathognomonic of CADASIL. The proband's older son and younger son have histories of migraine and depression, respectively, and both also had learning disorders. MRI revealed diffuse white matter disease extending into the temporal lobes, and lacunar infarctions in these four nonhypertensive patients. Other family members have experienced migraine, recurrent stroke, dementia, and depression. CONCLUSIONS: CADASIL is a genetic basis for vascular dementia that may be manifest earlier in life than previously reported.

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.

Meta-analysis of the Hachinski Ischemic Score in pathologically verified dementias.

Our objectives were to investigate the utility of the Hachinski Ischemic Score (HIS) in differentiating patients with pathologically verified Alzheimer's disease (AD), multi-infarct dementia (MID), and "mixed" (AD plus cerebrovascular disease) dementia, and to identify the specific items of the HIS that best discriminate those dementia subtypes. Investigators from six sites participated in a meta-analysis by contributing original clinical data, HIS, and pathologic diagnoses on 312 patients with dementia (AD, 191; MID, 80; and mixed, 41). Sensitivity and specificity of the HIS were calculated based on varied cutoffs using receiver-operator characteristic curves. Logistic regression analyses were performed to compare each pair of diagnostic groups to obtain the odds ratio (OR) for each HIS item. The mean HIS (+/- SD) was 5.4 +/- 4.5 and differed significantly among the groups (AD, 3.1 +/- 2.5; MID, 10.5 +/- 4.1; mixed, 7.7 +/- 4.3). Receiver-operator characteristic curves showed that the best cutoff was < or = 4 for AD and > or = 7 for MID, as originally proposed, with a sensitivity of 89.0% and a specificity of 89.3%. For the comparison of MID versus mixed the sensitivity was 93.1% and the specificity was 17.2%, whereas for AD versus mixed the sensitivity was 83.8% and the specificity was 29.4%. HIS items distinguishing MID from AD were stepwise deterioration (OR, 6.06), fluctuating course (OR, 7.60), hypertension (OR, 4.30), history of stroke (OR, 4.30), and focal neurologic symptoms (OR, 4.40). Only stepwise deterioration (OR, 3.97) and emotional incontinence (OR, 3.39) distinguished MID from mixed, and only fluctuating course (OR, 0.20) and history of stroke (OR, 0.08) distinguished AD from mixed. Our findings suggest that the HIS performed well in the differentiation between AD and MID, the purpose for which it was originally designed, but that the clinical diagnosis of mixed dementia remains difficult. Further prospective studies of the HIS should include additional clinical and neuroimaging variables to permit objective refinement of the scale and improve its ability to identify patients with mixed dementia.

Treatment for the secondary prevention of stroke in older patients: the influence of dementia status.

OBJECTIVE: To investigate the influence of dementia status on treatment for the secondary prevention of stroke in older patients. DESIGN: Based on patient examinations and medical record review, we investigated the frequency of aspirin and/or warfarin use at hospital discharge for the prevention of recurrent stroke in older patients hospitalized with acute ischemic stroke. SETTING: A large academic medical center. PARTICIPANTS: A cohort of 272 patients, mean age 72.1 +/- 8.5 years. MEASUREMENTS: We performed neurologic examinations and reviewed medical records to investigate the effects of a clinical diagnosis of dementia and other potentially relevant factors on treatment with aspirin or warfarin at hospital discharge. RESULTS: Thirty-one patients (11.4%) were not prescribed aspirin or warfarin at hospital discharge. Logistic regression determined that dementia (odds ratio (OR) = 2.57, 95% confidence interval (CI), 1.04-6.30) was a significant independent determinant of nontreatment with aspirin or warfarin, adjusting for abnormal gait (OR = 2.01, CI, .88-4.59); discharge to a nursing home or other institutional residence (OR = 2.55, CI, .83-7.81); cardiac disease (OR = .39, CI, .16-.95); cortical infarct location (OR = .45, CI, .18-1.10); male sex (OR = .47, CI, .20-1.15); age 80+ (OR = 1.14, CI, .46-2.82) and age 70-79 (OR = .96, CI, .32-2.88) versus age 60-69. CONCLUSIONS: Our results suggest that dementia is a significant independent determinant of nontreatment with aspirin or warfarin when otherwise indicated for the prevention of recurrent stroke. The underutilization of aspirin and warfarin in older stroke patients with dementia may be a modifiable basis for their increased risk of recurrence and death.

The role of routine laboratory studies and neuroimaging in the diagnosis of dementia: a clinicopathological study.

OBJECTIVE: To determine the neuropathological diagnoses of longitudinally followed patients with potentially reversible causes of dementia and to examine the results of the "dementia work-up," especially neuroimaging, by comparison with the pathological diagnosis. DESIGN: A neuropathologic series of 61 consecutive patients, with review of clinical, laboratory, neuroimaging, and pathological results. RESULTS: Of the 61 patients, forty-eight (79%) had a clinical diagnosis of probable or possible Alzheimer's disease (AD). Compared with the pathological diagnosis, the sensitivity and specificity of the clinical diagnosis of AD were 96% and 79%, respectively. Of the 61 patients, 9 had abnormal laboratory tests, the correction of which did not improve the subsequent course. These patients were found to have AD8 and frontotemporal dementia on pathology. In two patients, neuroimaging was helpful in the clinical diagnoses of frontotemporal dementia and progressive supranuclear palsy (PSP). Neuroimaging revealed cerebrovascular disease in 18 patients, only two of whom were suspected clinically. Pathology confirmed AD in 17 and PSP in 1 of these patients. Sensitivity and specificity for the clinical diagnosis of cerebrovascular disease in comparison with pathology were 6% and 98%, respectively. With the added information from neuroimaging, that sensitivity increased to 59% and specificity decreased to 81%. CONCLUSIONS: All cases with abnormal laboratory or neuroimaging results had AD or some other neurodegenerative disease on pathology. The "dementia work-up" did not reveal any reversible causes for dementia in this group of patients. Neuroimaging may have a role, especially in the diagnosis of possible AD with concomitant cerebrovascular disease.

Traumatic bilateral carotid dissection with concomitant cerebral infarction.

A 40-year-old man presented with a major nondominant hemisphere stroke syndrome after a road traffic accident. Cranial computed tomography scan revealed an extensive right hemisphere infarction involving the entire anterior and middle cerebral artery territories. Duplex Doppler ultrasound and cerebral angiography revealed bilateral internal carotid artery dissection with evidence of underlying fibromuscular dysplasia. Anticoagulation with heparin was commenced despite the coexisting large cerebral infarction, with the objective of protecting the uninjured but at-risk left cerebral hemisphere from ischemic injury. Patients with multiple cerebral arterial dissections complicated by cerebral infarction present a significant management dilemma. Our literature review revealed a lack of clear management guidelines for such cases.

Evaluation of stroke management in an Irish university teaching hospital: the Royal College of Physicians stroke audit package.

BACKGROUND: There are few data regarding the standard of stroke care in Ireland. AIM: To investigate the level of documentation for 13 key areas of stroke management. METHODS: Using a validated stroke audit package, this study reviewed the medical records of 100 consecutive patients hospitalised with acute stroke. RESULTS: Documentation of stroke symptoms, risk factors, general examination and investigations (cranial computer tomography [CT] and carotid Dopplers) were satisfactory. Neurological documentation was variable, with power (87%), sensation (70%) and eye movements (63%) being the most frequently recorded features, while cognition (3%), visual fields (13%), gait (7%), incontinence (1%) and swallowing (0%) were infrequently recorded. Diagnostic formulation and an acute management plan were documented in less than half of patients, whereas cranial CT (93%) and carotid Dopplers (93%) were well documented. Secondary preventive measures were documented in two-thirds of patients at follow-up. CONCLUSIONS: These results serve as a baseline from which to initiate and monitor improvements in the service at our hospital, including the involvement of neurologists in stroke care, and will also allow assessment of the impact of such changes.

Patient and hospital delays in acute ischaemic stroke in a Dublin teaching hospital.

A limiting factor for thrombolysis in ischaemic stroke is delayed presentation to hospital. Prolonged A&E stay and delayed rehabilitation affects care. We evaluated the delay in presentation, A&E stay and rehabilitation delivery in 117 consecutive stroke patients. The mean presentation delay was 16.0 +/- 23.7 hours. A prior history of TIA or stroke, a reduced Glascow Coma Scale and larger strokes were associated with shorter delays to presentation. Longer delays occurred in patients living alone. The mean time spent in A&E was 11 hours, those with larger strokes spent shorter time. There were significant delays in referral to, and assessment by certain rehabilitation disciplines. Delayed presentation in stroke is a barrier to thrombolysis. Increasing public awareness may reduce this delay. In addition, prolonged A&E stay and delayed rehabilitation may adversely affect management, outcome and duration of hospital stay. Further study is required to investigate the reasons and possible solutions for such deficiencies.

Recovery of cognitive function after stroke.

BACKGROUND AND PURPOSE: Previous studies have suggested that recovery of cognitive function after stroke is maximal within the first 3 months after onset. We performed the present study to investigate the long-term course and clinical correlates of improvement in generalized cognitive function after ischemic stroke. METHODS: We administered a battery of neuropsychological tests to 151 patients (age, 70.4 +/- 7.7 years; education, 10.4 +/- 4.6 years) at 3 months and then annually after stroke. We transformed their test results into z scores based on the performance of a stroke-free normative group, averaged those scores to create a summary score, and defined improvement in annual examinations as an increase in that summary score greater than two standard deviations above the mean first annual change of the normative group. We then used logistic regression to determine whether stroke location, syndrome, or recurrence; vascular risk factors; dementia status; depression; or demographic variables were associated with improvement. RESULTS: We found that 19 of the 151 patients exhibited improvement, which was evident only at the first annual examination in most cases. Logistic regression determined that improvement was significantly related to left hemisphere infarction relative to brain stem/cerebellar infarction (odds ratio [OR], 5.57), while the presence of a major hemispheral stroke syndrome showed a trend toward significance (OR, 3.32). Diabetes mellitus was significantly associated with a failure to exhibit improvement (OR, 0.12). Based on the logistic model, the probability of long-term improvement would be 54.0% for a patient with a left hemisphere infarct and a major hemispheral syndrome but only 11.9% if diabetes was also present. CONCLUSIONS: Long-term improvement in generalized cognitive function may be evident after stroke in association with left hemisphere infarction and severe hemispheral syndromes, while it may be compromised by diabetes, possibly because of an increased burden of cerebrovascular disease.

Dementia as a predictor of adverse outcomes following stroke: an evaluation of diagnostic methods.

BACKGROUND AND PURPOSE: Although it is understood that dementia is a risk factor for adverse outcomes, little is known about the predictive validity of the numerous methods that have been proposed for its diagnosis. Thus, we performed the present study to assess the utility of a variety of diagnostic methods in the prediction of adverse outcomes following stroke. METHODS: We administered neuropsychological, neurological, and functional examinations to 244 patients (age, 71.7+/-8.5 years) 3 months after ischemic stroke. We diagnosed dementia using each of the following methods: (1) neuropsychological testing, requiring deficits in increasing numbers of cognitive domains, both with and without memory impairment, as well as functional impairment; (2) Mini-Mental State Examination (MMSE) score of <24; and (3) neurologists' clinical judgment. We then used survival analyses to investigate the ability of diagnoses based on those methods to predict death and recurrent stroke during long-term follow-up. RESULTS: Log-rank tests and Cox proportional hazards analyses, with recurrent stroke entered as a time dependent covariate, determined that all of the paradigms were significant predictors of mortality, but the performance of paradigms based on neuropsychological testing was superior to the use of the MMSE and clinical judgment, particularly when memory impairment was required. Log-rank tests determined that paradigms based on neuropsychological testing were the only significant predictors of recurrent stroke and performed best when memory impairment was required. CONCLUSIONS: Our results suggest that dementia diagnosis based on neuropsychological assessment and an operationalized paradigm requiring deficits in memory and other cognitive domains is superior to other conventional methods in its ability to identify patients at elevated risk of adverse outcomes following stroke.

Risk factors for early recurrence after ischemic stroke: the role of stroke syndrome and subtype.

BACKGROUND AND PURPOSE: Information regarding risk factors for early recurrence is limited. Our aim was to identify the clinical predictors of early recurrence after ischemic stroke. METHODS: We prospectively examined 297 patients (mean age, 72.0+/-8.4 years) hospitalized with ischemic stroke to identify recurrent strokes occurring within 90 days of the index stroke. Survival free of recurrence was estimated using Kaplan-Meier analysis stratified by demographic variables; vascular risk factors; stroke syndrome, subtype, vascular territory, and severity; scores on the Barthel Index and Mini-Mental State Examination during hospitalization; blood pressure on admission; and selected laboratory data. We estimated the relative risk (RR) of early recurrence associated with those variables using proportional hazards analysis. RESULTS: We identified 22 recurrent events in the first 90 days after the index stroke, resulting in an early stroke recurrence rate of 7.4%, and death occurred immediately after recurrence in 6 of the 22 patients. A major hemispheric stroke syndrome (RR=2.9; 95% confidence interval [CI]=1.2 to 7.1), atherothrombotic stroke mechanism (RR=3.3; CI=1.3 to 8.3), and atrial fibrillation (RR=2.2; CI=0.8 to 6.1) were independent predictors of early recurrence, after adjustment for demographic variables. Conclusions-Early recurrence was frequent and resulted in increased mortality. Attention to the clinical features of the index stroke, including the presenting syndrome and the ischemic mechanism, and the recognition of atrial fibrillation may help in the selection of patients for the initiation of targeted interventions to prevent early recurrence and subsequent mortality.