J. Lodder

Predictive Accuracy of MCI Subtypes for Alzheimer’s Disease and Vascular Dementia in Subjects with Mild Cognitive Impairment: A 2-Year Follow-Up Study

Aim: The aim of this study was to investigate the prognostic accuracy of different subtypes of mild cognitive impairment (MCI): amnestic MCI, multiple domain MCI, and single non-memory domain MCI, for the development of Alzheimer’s dementia (AD) and vascular dementia (VaD). Patients: Nondemented patients from a memory clinic cohort (n = 118), and a stroke cohort (n = 80, older than 55 years and with a cognitive impairment). Results: ‘Multiple domain MCI’ had the highest sensitivity for both AD (80.8%) and VaD (100%), and ‘amnestic MCI’ had the highest specificity (85.9% for AD, 100% for VaD). The positive predictive value was low for all subtypes (0.0–32.7%), whereas the negative predictive value was high (72.8–100%). Discussion: The subtype ‘multiple domain MCI’ has high sensitivity in identifying people at risk for developing AD or VaD. The predictive accuracy of the MCI subtypes was similar for both AD and VaD.

Are hypertension or cardiac embolism likely causes of lacunar infarction

We tested the hypothesis that hypertension is more common and cardiac embolism less common in patients with lacunar infarction than in patients with other types of cerebral infarction. We studied risk factor profiles in a series of 102 consecutive patients with a lacunar infarct and 202 consecutive patients with a carotid artery-distribution infarct involving the cortex registered in the Oxfordshire Community Stroke Project, a community-based study of first-ever stroke. The two groups did not differ in the prevalence of prestroke hypertension (defined in a number of ways) or in the prevalence of markers of sustained hypertension. The presence of atrial fibrillation and a history of myocardial infarction, particularly during the 6 weeks before the stroke, were significantly more common in the group with carotid-distribution infarcts involving the cortex. There was no significant difference in the prevalence of other accepted risk factors for ischemic stroke, including previous transient ischemic attack, cervical bruit, diabetes mellitus, peripheral vascular disease, or cigarette smoking. Our results suggest that hypertension is no more important in the development of lacunar infarction than it is in the development of other types of ischemic stroke that are presumed to be due to atherosclerotic thromboembolism in a major cerebral artery. Our data support the autopsy evidence that cardioembolic occlusion is an unusual cause of lacunar infarction.

A comparative study into the one year cumulative incidence of depression after stroke and myocardial infarction

Background: The high incidence of post-stroke depression has been claimed to reflect a specific, stroke related pathogenesis in which lesion location plays an important role. To substantiate this claim, post-stroke depression should occur more often than depression after another acute, life threatening, disabling disease that does not involve cerebrovascular damage. Objectives: To compare the cumulative one year incidence of depression after stroke and after myocardial infarction, taking into consideration differences in age, sex, and the level of handicap. Methods: In a longitudinal design, 190 first ever stroke patients and 200 first ever myocardial infarction patients were followed up for one year. Depression self rating scales were used as a screening instrument to detect patients with depressive symptoms. Major and minor depression was assessed at one, three, six, nine, and 12 months after stroke or myocardial infarction according to DSM-IV criteria, using the structured clinical interview from DSM-IV. The severity of depressive symptoms was measured with the Hamilton depression rating scale. Level of disability and handicap was rated with the Rankin handicap scale. Results: The cumulative one year incidence of major and minor depression was 37.8% in stroke patients and 25% in patients with myocardial infarction (hazard ratio 1.6; p = 0.06). This difference disappeared after controlling for sex, age, and level of handicap. In addition, no differences were found in the severity of depressive symptoms or in the time of onset of the depressive episode after stroke or myocardial infarction. Conclusions: Depression occurs equally often during the first year after stroke and after myocardial infarction when non-specific factors such as sex, age, and level of handicap are taken into account. Thus the relatively high incidence of post-stroke depression seems not to reflect a specific pathogenic mechanism. Further research is needed to investigate whether vascular factors play a common role in the development of depression after stroke and myocardial infarction.

Virchow-Robin spaces relate to cerebral small vessel disease severity

Background and purposeVirchow-Robin spaces (VRs) are perivascular spaces surrounding the deep perforating brain arteries. VRs dilatation is pathologic, and it could be a manifestation of cerebral small vessel disease. In the present study we assessed the relation between VRs and silent ischemic lesions in a cohort of patients with cerebral small vessel disease.MethodsWe divided dilated VRs on MRI (1.5 Tesla) into three semi-quantitative categories in 165 first ever lacunar stroke patients. We counted asymptomatic lacunar infarcts and graded white matter lesions, and compared the prevalence of vascular risk factors in different categories of VRs. We also determined independent predictors of silent ischemic lesions.ResultsVRs at basal ganglia level related to age, hypertension, asymptomatic lacunar infarcts, and white matter lesions. VRs at basal ganglia level predicted silent ischemic lesions (odds ratio 10.58 per higher VRs category; 95 %- confidence interval 3.40 – 32.92).ConclusionDilated VRs in the basal ganglia relate to the severity of cerebral small vessel disease and might be a manifestation of the same small vessel abnormality that causes silent ischemic lesions. This adds a role for VRs as a potential marker for small vessel disease.

Demographic and CT scan features related to cognitive impairment in the first year after stroke

Objective: Little is known about the relation between stroke related features and cognitive performance over time when stroke patients with dementia or less severe cognitive disorders are considered separately. We aimed to study the features (computed tomography (CT) scan and demographic) that could be related to vascular cognitive impairment one, six, and 12 months after stroke. Methods: A total of 176 patients with a first-ever brain infarct, a Mini Mental State Examination score ⩾15, age older than 40 years, and without pre-stroke dementia and other neurological or psychiatric disorders participated in this study. The following CT scan features were recorded: side of infarct, lacunar or territorial infarct, white matter lesions, silent infarcts, and brain atrophy. The demographic features studied were: age, level of education, and sex. Univariate and multivariate logistic regression analyses were performed to compare the three groups of patients (patients with dementia, patients with vascular cognitive impairment (VCI), and patients with vascular mild cognitive impairment (MCI)) with patients without cognitive disorders. Results: At one month none of the variables were predictors of dementia; at six months older age (odds ratio (OR) 9.4), low education (OR 14.7), and territorial infarct (OR 10.6) predicted dementia; and at 12 months low education (OR 8.7) and pre-stroke cerebrovascular damage (OR 7.4) predicted dementia. Predictors of VCI were low education (OR 3.4) and territorial infarct (OR 2.4) at one month post stroke; older age (OR 4.3) and low education (OR 4.1) at six months; and older age (OR 3.5) at 12 months. Predictors of vascular MCI were low education (OR 4.96) and territorial infarct (OR 3.58) at one month; and older age and lower education at six months (OR 3.4 and 3.7, respectively) and at 12 months (OR 3.5 and 2.28, respectively). Conclusions: Territorial infarct, older age, and low educational level are predictors of cognitive disorders after stroke.

Thrombolysis for acute stroke with special emphasis on the very old: experience from a single Dutch centre

The aim of this study was to describe the clinical experience in 184 consecutive stroke patients first-ever treated with recombinant tissue plasminogen activator (rt-PA) at a single Dutch centre, with special emphasis on results among the very old. Outcome parameters were the modified Rankin scale (mRs) at 3 months and symptomatic intracranial haemorrhage (SICH). Outcome was related to age. A total of 184 patients were treated of whom 45 were 80 years of age or older (24%). Sixty two (45%) of 139 patients <80 years of age and 12 (27%) of 45 patients ⩾80 years of age had a favourable outcome defined as an mRs score of 0 or 1 (OR 2.21; 95% CI: 1.06 to 4.46). There was a good outcome (mRs score ⩽2) in 88 (63%) and 16 (36%) patients, respectively (OR 3.13; 95% CI: 1.55 to 6.30). SICH was observed in four of 139 (2.9%) patients <80 years of age and in five of 45 (11.1%) patients ⩾80 years of age (OR 4.22; 95% CI: 1.08 to 16.46). The results of this study underline the uncertainty regarding the risk/benefit ratio of rt-PA treatment in acute stroke in patients over 80 years of age.

Research into the specificity of depression after stroke: a review on an unresolved issue

Iwo decades of research have failed to generate consistent insight into the specificity of poststroke depression (PSD). This is, at least in part, caused by methodological difficulties. Differences in symptom profile between PSD and depression with no or another medical cause were described, but no specific and unequivocal clinical picture has been established so far. Prevalence rates of PSD varied largely between studies. In community based studies using standardised diagnostic instruments for depression, relatively low prevalence rates were reported compared to inpatient or rehabilitation studies. PSD occurs most frequently in the first few months after stroke, while a new incidence peak may occur 2-3 years after stroke. Two systematic reviews on the relation between lesion location and depression did not support the claim that left hemisphere lesions are a risk factor for PSD. A new concept of vascular depression has been proposed, which relates depression in the elderly to acute or chronic damage to the cerebral vascular system. Future efforts should aim at increasing the uniformity of study designs, assessment tools should be further improved for use in cognitively impaired patients and appropriate control groups should be defined to study the characteristic features of PSD.

Brain Microbleeds Are Associated With Ambulatory Blood Pressure Levels in a Hypertensive Population

Brain microbleeds, indicative of cerebral small-vessel disease, may occur with increased frequency in patients with hypertension. However, little is known about the relation of these abnormalities with blood pressure levels. We assessed the relation between ambulatory measured blood pressure and the presence of microbleeds in a cohort of hypertensive patients without a history of cerebrovascular disease. A total of 218 participants (110 males, age 52.5±12.6 years) underwent 24-hour ambulatory blood pressure monitoring twice (off-medication) and brain MRI to detect microbleeds and coexisting white matter hyperintensities. We performed logistic regression analyses to relate the following blood pressure components (based on both recordings) to microbleeds: the mean 24-hour, awake, and asleep blood pressures; nocturnal hypertension (asleep pressure ≥120/70 mm Hg); nocturnal blood pressure dipping. Models were adjusted for age and sex, and additionally for cardiovascular risk factors and white matter hyperintensities. We detected microbleeds in 35 participants (16.1%; 95% confidence interval, 11.1% to 21.0%). On average, each standard deviation increment in blood pressure, whether 24-hour, awake, or asleep, was significantly and independently associated with a 1.8- to 1.9-fold higher likelihood for microbleeds (all models P<0.05). Similarly, the adjusted odds ratio for microbleeds was 5- to 6-fold higher in subjects diagnosed with nocturnal hypertension (all models P<0.05). Microbleeds were not associated with nocturnal dipping. In conclusion, brain microbleeds are frequently found in hypertensive patients without a history of cerebrovascular disease, and are independently associated with higher daytime as well as night-time blood pressure levels.

Vascular cognitive disorders: Memory, mental speed and cognitive flexibility after stroke

This study investigated the occurrence of cognitive disorders 1 and 6 months after stroke in a cohort of patients with a first-ever stroke. In addition, it was investigated whether age, sex and level of education are risk factors for vascular cognitive disorders. Memory, simple speed, cognitive flexibility and overall cognitive functioning were examined in 139 patients at 1 and 6 months post-stroke. Inclusion criteria on admission were first cerebral stroke, age>/=40, no other neurological or psychiatric disorders and ability to communicate. Mean age was 69.3 years (S.D.=12.3). Patients were compared with a healthy control group matched for age, sex and level of education. A large group of patients who, at 1 month after stroke, scored below the cutoff on cognitive domains, scored above the cutoff on most of these cognitive domains at 6 months. For overall cognitive functioning, 16 out of 39, for memory, 13 out of 26 and for cognitive flexibility, 15 out of 49 patients, who at 1 month scored below the cutoff, scored above the cutoff at 6 months. Simple speed did not change; 12 patients scored above the cutoff and 7 patients scored below the cutoff at 6 months after stroke. Speaking in terms of improvement or deterioration, most people remained stable on the four cognitive domains (ranging from 37.6% to 83.5%), and a substantial group improved (ranging from 12.9% to 52.1%). Older and female patients had more cognitive disturbances. Overall, the conclusion is that the prognosis of cognitive functioning after stroke is general favourable, especially in younger patients.

The diagnosis of epileptic and non-epileptic seizures

The aim of this prospective population-based study was to systematically define a cluster of diagnostic items which can assist in the early identification and classification of epileptic and non-epileptic seizures. A cohort of patients aged > or =14 years, suspected with a first epileptic seizure, were included in this study. A team of neurologists evaluated and classified all cases. Diagnostic items for epileptic and non-epileptic seizures were identified using logistic regression analysis. Three hundred and fifty cases entered this study. Distinctive features for epileptic seizures were postictal confusion (OR 0.09), an epileptiform EEG pattern (OR 0.02), and abnormal neuroimaging findings (OR 0.07), whereas for non-epileptic seizures of organic origin there was a history of hypertension (OR 7.5), and provoking factors (OR 13.4) such as exercise and warmth. Diagnostic items for seizures of non-organic origin were a history of febrile seizures (OR 5.8), treatment by a psychologist or psychiatrist (OR 9.1), and presentiment of the seizure (OR 3.7) such as a feeling of choking and palpitations. A separate analysis for the patients who were systematically investigated provided some additional diagnostic items for the different subgroups of patients. For instance, back arching during the seizure for the patients with seizures of non-organic origin and female sex for the patients with non-epileptic seizures of organic origin.