Vascular cognitive syndromes: relation to stroke etiology and topography

Background – Cognitive syndromes (CS) after stroke may be important to measure and monitor for management and emerging therapies. Aim – To describe the spectrum and frequency of CSs in the first month after stroke and to relate these to stroke etiology and topopgraphy. Methods – A validated cognitive examination was administered during the first month of stroke presentation and analyzed according to five large‐scale networks for cognition and correlated with neuropsychological tests. A multivariate analysis was performed to determine association of CSs with etiology (TOAST classification), topography and neurological deficit by National Institute of Health Stroke Score (NIHSS). Results – Of a total of 2105 patients, one or more patients with CS was present in 1569/1796 (87%) stroke patients vs 112/309 (36%, P ≤ 0.001) transient ischemic attack (TIA) patients. The frequency of frontal network syndromes (FNS) was 908/1796 (51%), left hemisphere network (LH) syndromes 646/1796 (36%), right hemisphere (RH) network syndromes 275/1796 (15.3%), occipitotemporal network (OT) syndromes 107/1796 (6%), hippocampal limbic (HL) network syndromes 397/1796 (22%) and miscellaneous (M) syndromes 481/1796 (27%). Stroke etiology and their signature CS by multivariate analyses revealed significant associations for LH with cardioembolism (OR 1.61, P = 0.0029), FNS and ‘other’ etiology (OR 1.96, P ≤ 0.0001) and HL also for ‘other’ etiology (OR 1.57, P = 0.0026). Coma (OR 2.95, P ≤ 0.0001) and encephalopathy (OR 2.82, P ≤ 0.0001) were both associated significantly with hemorrhage. A left hemisphere lesion was associated with LH CSs (OR 9.26, P ≤ 0.0001). An FNS was associated with frontal lesions (OR 5.19, <0.0001) as well as subcortical lesions (OR 1.91, P ≤ 0.0001). The M group of CS was associated with subtentorial (OR 1.86, P = 0.0283) and right hemisphere lesions (OR 2.47, P ≤ 0.0001). The LH and RH syndromes had the highest NIHSS and differed significantly from all others. Conclusions – (1) CSs are present in the vast majority of stroke patients. (2) Particular stroke etiological subtypes are associated with specific CS. (3) Certain signature CS results from lesions that relate to the major anatomical cognitive networks.     

Alcoholic cognitive deterioration and nutritional deficiencies

Chronic alcoholic patients frequently exhibit a mild to moderate cognitive impairment that has been related to Wernicke-Korsakoff encephalopathy and attributed tentatively to nutritional and vitamin deficiencies. To elucidate the posible relation between alcoholic cognitive deterioration (ACD) and nutritional and vitamin deficiencies, several tests of intelligence and memory were administered to 54 chronic alcoholic patients and 30 controls. Serum levels of thiamine, folic acid, vitamins B12, A, and E, and certain nutritional indexes were determined in most of the subjects. The alcoholics scored significantly lower in intellectual and visuospatial tasks but not in verbal memory tasks. They had a lower serum level for thiamine but not of the remaining vitamins. However, the correlations between serum thiamin and cognitive performance scores were low, and according to stepwise regression analysis, duration of alcohol intake and education were the variables with predictive value for intellectual and memory test performance. These results suggest that serum thiamin deficiency is not the main pathogenetic factor related to ACD.     

Vascular cognitive impairment in patients with late-onset seizures after an ischemic stroke

BACKGROUND: Cognitive impairment and seizures are both common conditions in patients with cerebrovascular disease. PURPOSE: The present study investigates whether the occurrence of late-onset seizures, following an ischemic stroke, contributes to vascular cognitive impairment. PATIENTS AND METHODS: The mean Mini-Mental State Examination (MMSE) and the median modified Rankin (mR) scores were compared between 125 patients who developed late-onset seizures (66 with a single seizure and 59 with repeated seizures or epilepsy) following an ischemic stroke and 125 patients who did not during, at least, a 2-year follow-up. RESULTS: There were no differences in age, gender, etiology and degree of neurological impairment on admission for their stroke between the groups with and without seizures. Although the mean MMSE score was similar between both groups the median mR score was significantly higher in the seizure patients. Comparing the patients with a single seizure to the non-seizure ones showed the same results. On the other hand, comparison of the patients with epilepsy to the non-seizure group revealed, in addition to the higher median mR score, a significantly lower mean MMSE score in the former group. CONCLUSION: Repeated seizures following an ischemic stroke promote vascular cognitive impairment.     

Vascular cognitive impairment

Cerebrovascular disease is the second most common cause of acquired cognitive impairment and dementia and contributes to cognitive decline in the neurodegenerative dementias. The current narrow definitions of vascular dementia should be broadened to recognise the important part cerebrovascular disease plays in several cognitive disorders, including the hereditary vascular dementias, multi-infarct dementia, post-stroke dementia, subcortical ischaemic vascular disease and dementia, mild cognitive impairment, and degenerative dementias (including Alzheimer's disease, frontotemporal dementia, and dementia with Lewy bodies). Here we review the current state of scientific knowledge on the subject of vascular brain burden. Important non-cognitive features include depression, apathy, and psychosis. We propose use of the term vascular cognitive impairment, which is characterised by a specific cognitive profile involving preserved memory with impairments in attentional and executive functioning. Diagnostic criteria have been proposed for some subtypes of vascular cognitive impairment, and there is a pressing need to validate and further refine these. Clinical trials in vascular cognitive impairment are in their infancy but support the value of therapeutic interventions for symptomatic treatment.     

Acute stroke unit care and early neurological deterioration in ischemic stroke

OBJECTIVE: To evaluate the impact that monitored acute stroke unit care may have on the risk of early neurological deterioration (END), and 90-day mortality and mortality-disability. METHODS: Non-randomized prospective study with consecutive patients with acute ischemic stroke (AIS) admitted to a conventional care stroke unit (CCSU), from May 2003 to April 2005, or to a monitored acute stroke unit (ASU) from May 2005 to April 2006. END was defined as an increase in the NIHSS score >or= 4 points in the first 72 hours after admission. RESULTS: END was detected in 19.6% of patients (11.2% of patients admitted to the ASU and 23.8% to the CCSU; p<0.0001). Patients admitted to the ASU received more treatment with intravenous rtPa (13.5% versus 4.2%; p<0.0001), had a shorter length of stay (9.1 [11.0] d versus 13.1 [10.4] d; p<0.0001), lower 90-day mortality (10.2% versus 17.3%; p=0.02), and lower mortality-disability at 90-days (28.4% versus 40.2%; p=0.004) than those admitted to the CCSU. Multivariable analysis showed that ASU admission was a protector for END (OR: 0.37; 95% CI: 0.23-0.62). On admission, higher NIHSS (OR: 1.06; 95% CI: 1.03-1.10), higher glycaemia (OR: 1.003; 95% CI: 1.001-1.006), and higher systolic pressure (OR: 1.01; 95% CI: 1.002-1.017) were independent predictors of END. CONCLUSIONS: END prevention by ASU care might be a key factor contributing to better outcome and decrease of length of stay in patients admitted to monitored stroke units.     

Vascular cognitive impairment

Cognitive impairment commonly accompanies clinical syndromes associated with vascular disease of the brain. Because of evolving definitional criteria, however, the frequency of cognitive impairment attributable to cerebrovascular disease is difficult to determine. Dementia occurs in up to one-third of elderly patients with stroke, a subset of whom have Alzheimer's disease (AD) rather than a pure vascular dementia syndrome. In fact, pure vascular dementia has been shown to be uncommon in most large autopsy series. A mixed etiology of AD and cerebrovascular disease is thought to become more common with increasing age, although no clinical criteria for the diagnosis of AD with cerebrovascular disease are currently available. Epidemiological studies have implicated subcortical small-vessel disease as a risk factor for cognitive impairment and dementia, but the cognitive expression and clinical significance of MRI white matter changes in individual patients is difficult to establish. The frequency of specific neuropathologic features of vascular cognitive impairment depends largely on study inclusion criteria. Cerebral meningocortical microangiopathies with distinctive clinicopathological profiles are associated with dementia in both sporadic cases and familial syndromes. In patients with AD, the contribution of amyloid-beta protein to the degree of cognitive impairment has not been clearly defined.     

Memory deficits and early cognitive deterioration in MS

Introduction – In the present study, the pattern of memory and learning deficits in two cognitively different, but clinically and demographically similar, multiple sclerosis (MS) groups was compared. Material & methods – 23 patients represented the cognitively preserved MS group and 22 patients the MS group with early cognitive decline. A control group of 35 healthy controls was also included. The cognitive status of the subjects was defined using the Mild Deterioration Battery (MDB). Furthermore, all subjects were given a set of memory and learning tests and were instructed to evaluate the frequency of their memory and learning difficulties. The Mini-Mental State Examination (MMSE) was also administered to all subjects. Results – The cognitively deteriorated patients, even those with normal MMSE performance, showed widespread memory and learning deficits, but adequate self-evaluation of their everyday memory and learning difficulties. The preserved group, in turn, performed similarly to the controls. Conclusion – Widespread memory and learning deficits are associated with relatively mild cognitive decline in MS. These deficits were observable in the intermediate-length screening battery, the MDB, but not in the MMSE. The present study suggests that the accuracy of patients'own evaluations of their memory and other cognitive problems is superior to the results of very brief screening batteries, like the MMSE. Therefore, brief screening in neuropsychological assessment of MS patients is not recommendable.     

Vascular cognitive impairment.

Cerebrovascular disease is increasingly recognized as a common cause of cognitive impairment and dementia in later life either alone or in conjunction with other pathologies, most often Alzheimer disease (AD). Progress in the field has been limited by difficulties in terminology; for example, use of the term dementia necessitates the presence of memory impairment, which is the norm in AD, but not in cognitive disorders associated with cerebrovascular disease. The term vascular cognitive impairment (VCI) has been proposed as an umbrella term to recognize the broad spectrum of cognitive, and indeed behavioral, changes associated with vascular pathology. It is characterized by a specific cognitive profile with predominantly attentional and executive impairments together with particular noncognitive features (especially depression) and a relatively stable course, at least in clinical trial populations. Subtypes of VCI have been proposed based on clinical and pathologic differences, including cortical, subcortical, strategic infarct, hypoperfusion, hemorrhagic, and mixed (with AD) type. Diagnostic criteria are emerging but require refinement and validation, especially for mixed dementias. There remain fundamental gaps in our understanding of pathophysiology, predicting prognosis and outcome, and in therapeutics. Clinical trials to date, mainly in populations selected using currently accepted criteria for vascular dementia, have generally been disappointing. A relatively modest cognitive benefit of agents such as nimodipine, memantine, and cholinesterase inhibitors has been reported, although the clinical significance of these improvements remains to be established. Further studies, focusing on particular subtypes of VCI and involving subjects at earlier stages of the disease, are required. The aim of this article is to review the concept of VCI in terms of the evidence base surrounding diagnosis, clinical features, pathophysiology, and management and to make some recommendations regarding further research in the area. It begins with a discussion on the historical background, which is important to understand the different and somewhat confusing terminology that currently exists in the field.     

Impaired cerebral glucose metabolism and cognitive functioning predict deterioration in mild cognitive impairment

The objective of this study was to assess whether reduced glucose metabolism (rCMRGlu) and cognitive functioning could predict development of Alzheimer's disease (AD) in subjects with mild cognitive impairment (MCI). Twenty MCI patients underwent baseline and follow-up investigations of rCMRGlu, as measured by PET, and cognitive function measured by neuropsychological test assessments. Subjects were clinically followed up with an average interval of 36.5 months. Two groups were obtained after the second clinical assessment. Nine patients were diagnosed as AD and classified as progressive MCI (P-MCI), whereas 11 patients remained clinically stable and were classified as stable MCI (S-MCI). There were no differences in demographic variables or baseline MMSE between the two subgroups. Logistic regression indicated the two variables that most effectively predicted future development of AD were rCMRGlu from the left temporoparietal area and performance on the block design. These combined measures gave an optimal 90% correct classification rate, whereas only rCMRGlu or neuropsychology alone gave 75% and 65% correct classification, respectively. Measures of temporoparietal cerebral metabolism and visuospatial function may aid in predicting the evolution to AD for patients with MCI.     

Vascular risk factors and cognitive disorders

Delaying the onset of dementia by just a few years could have a major impact on the prevalence of the disease at the population level. Vascular risk factors are modifiable and may offer an important opportunity for preventive approaches. Several studies have shown that diabetes, hypertension, obesity, and smoking are associated with an increased risk of cognitive decline and dementia, but other groups have not observed such a relation. Positive associations were observed mainly in studies where risk factors were assessed in midlife, suggesting that age is an important modulator in the relation between vascular risk factors and cognition. The population attributable risk of dementia is particularly high for hypertension. Associations of vascular risk factors with cognitive decline and dementia are probably mediated largely by cerebrovascular disease, including both stroke and covert vascular brain injury, which can have additive or synergistic effects with coexisting neurodegenerative lesions. To date, randomized trials have not convincingly demonstrated that treating vascular risk factors is associated with a reduction in cognitive decline or dementia risk. Of eight randomized trials testing the effect of antihypertensive agents on dementia risk, only one was positive, and another in a subgroup of individuals with recurrent stroke. In most trials, cognition and dementia were secondary outcomes, follow-up was short and treatment was initiated at an older age. No effect on cognitive decline or dementia could be demonstrated for statins and intensive glycemic control. Future areas of investigation could include differential class effects of antihypertensive drugs on cognitive outcomes and identification of high risk individuals as target population for clinical trials initiated in midlife.     

Neurological deterioration in patients with first-ever ischemic stroke

A study was conducted for 121 patients (55 female, 66 male; age 68.7 +/- 10.4 years) with first-ever ischemic stroke to investigate the frequency and risk factors of early neurological deterioration (ND). The initial evaluation was carried out within 24 hours of stroke onset. National Institutes of Health Stroke Scale score and Barthel index were used to evaluate patients for a period of 2 months. Thirty-eight patients (31.4%) showed early ND and 83 patients (68.6%) were stable or improved. Among the 38 patients with ND, 25 (65.8%) patients occurred within 48 hours after initial evaluation. In most patients, ND began on the first day and ceased on the third day after stroke onset. Neurological function started to improve after ND reaching the nadir. The mortality rate was 13.2% (5/38) for patients with ND and 1.2% (1/83) for patients without deterioration. At the end of the study, the functional ability and motility of patients were lower in the progressive group than in the non-progressive/stable group. Results of this study seem to indicate that an elevated C-reactive protein level and total anterior circulation infarction are risk factors for ND. The results also suggest that more aggressive and early treatments are needed for stroke patients to prevent disease progression.     

Late auditory evoked potentials in subcortical cognitive deterioration

Late auditory evoked potentials (AEPs) were recorded by the odd-ball method in 55 non-deteriorated parkinsonians (NP) and in 27 parkinsonians with cognitive deterioration (CDP), compared with 20 controls (C) and 24 patients with Alzheimer-type senile dementia (ATSD). The latency of P 300 was prolonged in the CDP and ATSD groups (410.72 +/- 24.45 and 433.62 +/- 38.30 respectively; P less than 0.001. The latency of N 100 was prolonged only in the CDP group (106.6 +/- 4.82; P less than 0.001). Late AEPs were also studied in 63 subjects with possible or confirmed disseminated sclerosis (DS) compared with 33 controls of similar mean age. The ERFC test divided these patients into 38 with non-deteriorated DS (NDS) and 25 with deteriorated DS (DDS). The latency of P 300 was prolonged in both groups: NDS 331.14 +/- 25.89; DDS 376.64 +/- 29.51 (P less than 0.001). The latency of N 100 was prolonged in the NDS group (100.25 +/- 9.20) and the DDS group (104.43 +/- 9.01). Following a study of correlations between the degree of mental deterioration and the electrophysiological parameters in these populations, the significance of the N 100 latency as electrophysiological marker of subcortical dementia is discussed.     

Hyperacute cognitive stroke syndromes

Cognitive syndromes are common clinical manifestations of hyperacute stroke and may be the single or dominant presenting features. They are related to acute dysfunction of complex integrated distributed functional networks serving different cognitive domains. The most common cortical syndromes include nonfluent or fluent aphasia, neglect, collor agnosia, pure alexia and Balint's syndrome. Disturbances of declarative memory are common following posterior cerebral artery and thalamic strokes. Abulia can follow thalamic, caudate and capsular lesions. Intraventricular and subarachnoid haemorrhages can cause preeminent neuropsychological changes. Disorientation is present in about 40 % of acute stroke patients and delirium complicates the course of 25 % of acute strokes. Some hyperacute cognitive stroke syndromes are useful indicators of later disability. Cognitive syndromes may pose special difficulties to neurology residents, unless formal teaching in neuropsychology and psychiatry is included in their training programs. Received: 25 April 2001, Accepted: 30 April 2001