Spouses' need for information and satisfaction with the patient's care and rehabilitation after stroke. Importance of depression and prescheduled follow-up.

OBJECTIVES: We aimed to study the information needs of the spouses of stroke survivors, and whether the functional ability, depressive mood, or demographic factors of the survivors or spouses associate with the information needs or satisfaction with care. We also investigated whether prescheduled follow-up improves information provision. METHODS: Ninety-six spouses of consecutive stroke survivors completed a questionnaire on their information needs and satisfaction with care 21 months post-stroke. The results of samples before (n = 59) and after (n = 37) the implementation of the prescheduled follow-up were compared. RESULTS: Before the follow-up, 75% of the spouses had received information on stroke and the well-being of the survivor, with 31% having received information on the survivors' and 18% on the spouses' own mood. The information provision improved after the follow-up: 86%, 44%, and 50%, respectively. The need for more information and satisfaction with care were associated with the spouse's depression, but not with functional impairment. CONCLUSIONS: Even if information on stroke is satisfactorily provided, the mood and well-being of spouses is often neglected. Information provision and support can be improved with systematic prescheduled follow-up. PRACTICE IMPLICATIONS: Our results suggest the routine assessment of the depressive symptoms and needs of spouses of stroke survivors.

Safety of alemtuzumab in a nationwide cohort of Finnish multiple sclerosis patients.

BACKGROUND: Alemtuzumab is an effective disease-modifying therapy (DMT) for highly active multiple sclerosis (MS). However, safety concerns limit its use in clinical practice. OBJECTIVES: To evaluate the safety of alemtuzumab in a nationwide cohort of Finnish MS patients. METHODS: In this retrospective case series study, we analyzed the data of all but two MS patients who had received alemtuzumab in Finland until 2019. Data were systematically collected from patient files. RESULTS: Altogether 121 patients were identified, most of whom had received previous DMTs (82.6%). Median follow-up time after treatment initiation was 30.3 months and exceeded 24 months in 78 patients. Infusion-associated reactions (IARs) were observed in 84.3%, 57.3%, and 57.1% of patients during alemtuzumab courses 1-3, respectively. Serious adverse events (SAEs) were observed in 32.2% of patients, serious IARs in 12.4% of patients, and SAEs other than IARs in 23.1% of patients. Autoimmune adverse events were observed in 30.6% of patients. One patient died of hemophagocytic lymphohistiocytosis, and one patient died of pneumonia. A previously unreported case of thrombotic thrombocytopenic purpura was documented. CONCLUSIONS: SAEs were more frequent in the present cohort than in previous studies. Even though alemtuzumab is a highly effective therapy for MS, vigorous monitoring with a long enough follow-up time is advised.

Implementation of Prescheduled Follow-Ups With Education Improve Poststroke Depression Screening Compliance in Routine Clinical Practice.

OBJECTIVES: To investigate the extent to which the mood of stroke patients is assessed and what kind of assessment methods are used in routine clinical practice, and whether prescheduled follow-ups can improve the detection of depression, particularly when this practice is blended with better education for health care professionals in assessing and detecting depression. DESIGN: Before-after trial with an 18-month follow-up and a review of medical records. SETTING: Acute care hospital, community. PARTICIPANTS: Consecutive acute stroke patients (N=398) were screened. Patients lived in a health care district with a population of 132,000. The screening took place in the first half of 2010 and then again, after the implementation of the follow-up system, in the first half of 2012. After exclusion of patients too severely ill to be interviewed, there were n=105 patients in the 2010 sample and n=112 patients in the 2012 sample. INTERVENTION: Implementation of a follow-up path for all stroke patients. MAIN OUTCOME MEASURES: The percentage and quality of mood assessments in the medical records; and the stroke patients' depressive symptoms and their satisfaction with their care. RESULTS: In the 2010 sample, 47% of the patients (n=48) had documentation of mood in their medical records. After the implementation of prescheduled follow-ups, 77% of the patients (n=86) had documented moods. The increase was highly significant (P<.001). During the early outpatient phase, the use of interviews increased from 14% (n=15) to 45% (n=50) of the patients (P<.001). The increase in the satisfaction with care did not reach statistical significance. Depressive symptoms recorded at any time were associated with depressive symptoms at 18 months (P<.001). CONCLUSIONS: Prescheduled follow-ups for all stroke patients, including routine depression screening, can remarkably improve the compliance with depression screening and the detection of depression.

Left atrial appendage volume increased in more than half of patients with cryptogenic stroke.

BACKGROUND: Ischemic strokes without a well-defined etiology are labeled as cryptogenic, and account for 30-40% of strokes in stroke registries. The left atrial appendage (LAA) is the most typical origin for intracardiac thrombus formation when associated with atrial fibrillation. Here, we examined whether increased LAA volume detected with cardiac computed tomography (cCT) constitutes a risk factor in cryptogenic stroke patients. METHODS: This study included 82 stroke/TIA patients (57 males; mean age, 58 years) with a diagnosis of cryptogenic stroke after extensive radiological and cardiological investigations. Cases were classified using the TOAST criteria modified by European Association of Echocardiography recommendations for defining cardiac sources of embolism. Forty age- and gender-matched control subjects without cardiovascular diseases were selected for pair-wise comparisons (21 males; mean age, 54 years). LAA volume adjusted for body surface area was measured three dimensionally by tracing the LAA borders on electrocardiogram-gated CT slices. RESULTS: In control subjects, mean LAA volume was 3.4±1.1 mL/m(2). Mean+2SD, which was considered the upper limit for normal LAA volume was 5.6 mL/m(2). In paired Student t-test between the patient group and matched controls, LAA volume was 67% larger in cryptogenic stroke/TIA patients (5.7±2.0 mL/m(2) vs. 3.4±1.1 mL/m(2); P<0.001). Forty-five (55%) patients with cryptogenic stroke/TIA had enlarged LAA. CONCLUSION: LAA is significantly enlarged in more than half of patients with cryptogenic stroke/TIA. LAA thrombosis may contribute to the pathogenesis of stroke in patients considered to have cryptogenic stroke after conventional evaluation.

[Impaired vision-dependent performance due to posterior cortical atrophy]. / Keski-ikäisen naisen hahmottamisongelmat posteriorisen kortikaalisen atrofian oireina.

By causing problems in vision-dependent perception, posterior cortical atrophy (PCA) results in a significant impairment of functional ability. Most cases of PCA are atypical manifestations of Alzheimer's disease. PCA is a rare disease, and accurate data about its frequency are lacking. Disease symptoms begin typically under the age of 60 years. The prerequisites for a correct diagnosis are awareness and recognition of a special clinical picture and special investigations such as cerebrospinal fluid analysis and investigations of brain metabolism. A typical set of clinical characteristics and findings of special examinations in PCA are described.

[Use of CSF biomarkers in the diagnostics of memory diseases]. / Alzheimerin taudin merkkitekijöiden käyttö muistisairauksien diagnostiikassa.

Alzheimer's disease is the most common cause of dementia. Early diagnosis of diseases leading to dementia is cost-effective. However, early diagnosis of Alzheimer's disease may be difficult and should not be based on exclusion of other reasons for dementia. A decreased CSF amyloid beta-peptide-42 level together with elevated tau or phosphorylated tau levels can differentiate patients with AD from control subjects or patients with other neurologic conditions with relatively high accuracy. We evaluated the use of these biomarkers in 452 patient cohort during 2005-2007 in clinical practice. Cerebrospinal fluid biomarkers seem to be useful especially to confirm Alzheimer's disease diagnosis.

Cerebrospinal fluid {beta}-amyloid 42 and tau proteins as biomarkers of Alzheimer-type pathologic changes in the brain.

BACKGROUND: There is a clear need to develop an objective diagnostic test for Alzheimer disease (AD). Changes in the levels of cerebrospinal fluid (CSF) tau protein and beta-amyloid 42 (Abeta42) peptide in patients with AD have been well documented, but the relationship between these biomarkers and neuropathologic changes in the brain is not established. OBJECTIVE: To study the relationship between antemortem CSF biomarker levels and Alzheimer-type neuropathologic changes in the brain. DESIGN: Cross-sectional study to correlate levels of CSF Abeta42, total tau, and phosphorylated tau protein with neuropathologic changes in the brain. SETTING: Academic research. Patients The study included 123 patients (79 with clinically diagnosed AD, 29 with other dementia, and 15 with other neurologic disease). All underwent clinical evaluation and provided antemortem lumbar CSF samples, and neuropathologic data were collected from September 11, 1990, to March 13, 2003, in the Department of Neuroscience and Neurology, University of Kuopio, Kuopio, Finland. MAIN OUTCOME MEASURES: Levels of CSF Abeta42, total tau, and phosphorylated tau protein were measured using standard commercial immunoassays. Neuropathologic evaluations included the classic silver impregnation method and immunohistochemistry for Abeta, hyperphosphorylated tau, and alpha-synuclein. RESULTS: Cerebrospinal fluid Abeta42 and tau protein levels were related to amyloid load and the presence of neurofibrillary pathologic abnormalities in the brain. Cerebrospinal fluid Abeta42 level correlated inversely with total Abeta load in the brain, and CSF tau level correlated with results of immunohistochemistry for hyperphosphorylated tau and with the presence of neocortical neurofibrillary tangles. In multivariate logistic regression analysis, the number of neuritic plaques in the brain remained a significant predictor of decreased CSF Abeta42 level and of increased CSF tau level. Based on the ratio of phosphorylated tau level to Abeta42 level, sensitivity was 91.6%, and specificity was 85.7%, with an overall accuracy of 90.2% for the presence of pathologic neuritic plaque in the brain. CONCLUSIONS: Cerebrospinal fluid Abeta42 and tau proteins are biomarkers of AD-associated pathologic changes in the brain. The combination of abnormally low CSF Abeta42 level and abnormally high CSF tau level predicted the presence of AD pathologic features with high accuracy. This combination assay may be helpful in diagnosing the presence of AD pathologic changes in the brain.

Assessment of beta-amyloid in a frontal cortical brain biopsy specimen and by positron emission tomography with carbon 11-labeled Pittsburgh Compound B.

OBJECTIVE: To compare carbon 11-labeled Pittsburgh Compound B ([11C]PiB) positron emission tomography (PET) findings in patients with and without Alzheimer disease lesions in frontal cortical biopsy specimens. DESIGN: Cross-sectional study of [11C]PiB PET findings in patients with or without beta-amyloid (Abeta) aggregates in frontal cortical biopsy specimens. SETTING: Two university hospitals in Finland. Patients Ten patients who had undergone intraventricular pressure monitoring with a frontal cortical biopsy (evaluated for Abeta aggregates and hyperphosphorylated tau) for suspected normal-pressure hydrocephalus. INTERVENTIONS: [11C]PiB PET and evaluation for cognitive impairment using a battery of neuropsychological tests. MAIN OUTCOME MEASURES: Immunohistochemical evaluation for Abeta aggregates and hyperphosphorylated tau in the frontal cortical biopsy specimen and [11C]PiB PET. RESULTS: In patients with Abeta aggregates in the frontal cortical biopsy specimen, PET imaging revealed higher [11C]PiB uptake (P < .05) in the frontal, parietal, and lateral temporal cortices and in the striatum as compared with the patients without frontal Abeta deposits. CONCLUSIONS: Our study supports the use of noninvasive [11C]PiB PET in the assessment of Abeta deposition in the brain. Large prospective studies are required to verify whether [11C]PiB PET will be a diagnostic aid, particularly in early Alzheimer disease.

MRI of hippocampus and entorhinal cortex in mild cognitive impairment: a follow-up study.

The concept of mild cognitive impairment (MCI) has been proposed to represent a transitional stage between normal aging and dementia. We studied the predictive value of the MRI-derived volumes of medial temporal lobe (MTL) structures, white matter lesions (WML), neuropsychological tests, and Apolipoprotein E (APOE) genotype on conversion of MCI to dementia and AD. The study included 60 subjects with MCI identified from population cohorts. During the mean follow-up period of 34 months, 13 patients had progressed to dementia (9 to Alzheimer's disease (AD)). In Cox regression analysis the baseline volumes of the right hippocampus, the right entorhinal cortex and CDR sum of boxes predicted the progression of MCI to dementia during the follow-up. In a bivariate analysis, only the baseline volumes of entorhinal cortex predicted conversion of MCI to AD. The Mini-Mental State Examination (MMSE) score at baseline, WML load, or APOE genotype were not significant predictors of progression. The MTL volumetry helps in identifying among the MCI subjects a group, which is at high risk for developing AD.

Differentiation of geriatric major depression from Alzheimer's disease with CSF tau protein phosphorylated at threonine 231.

OBJECTIVE: Differentiation of geriatric major depression from Alzheimer's disease is hampered by overlapping symptoms. Increased CSF concentrations of tau protein phosphorylated at threonine 231 (p-tau(231)) have been suggested as a biomarker for Alzheimer's disease. The authors asked whether p-tau(231) levels improve the differential diagnosis between geriatric major depression and Alzheimer's disease. METHOD: Included were 34 depression subjects, 64 with probable Alzheimer's disease, 17 with possible Alzheimer's disease, and 21 healthy comparison subjects. P-tau(231) concentrations were measured with an enzyme-linked immunosorbent assay. RESULTS: P-tau(231) levels were significantly higher in Alzheimer's disease than in geriatric major depression patients and healthy comparison subjects. For differentiation of probable Alzheimer's disease from major depression, p-tau(231) correctly allocated 87% of subjects. When possible mild Alzheimer's disease was compared to major depression, p-tau(231) correctly allocated 78% of subjects. CONCLUSIONS: CSF p-tau(231) should be evaluated as a potential biological marker for differentiation of geriatric depression from Alzheimer's disease.

Abeta levels in serum, CSF and brain, and cognitive deficits in APP + PS1 transgenic mice.

We compared beta-amyloid peptide (Abeta) levels in the serum, CSF and brain (hippocampus) and correlated these with spatial learning in APP+PS1 transgenic mice. Compared with non-transgenic littermates, male 14-month-old APP + PS1 mice were impaired in spatial learning in the water maze. Among the APP + PS1 mice, only the hippocampal insoluble Abeta42 level correlated with spatial memory (r = -0.44). The levels of insoluble Abeta40 and Abeta42 were highly correlated (r = 0.92), and also correlated with soluble hippocampal Abeta42 (r = 0.64/0.69), which further correlated with the CSF Abeta42 (r = 0.52). None of these parameters correlated with serum Abeta40 levels. These findings support the role of insoluble Abeta42 in memory dysfunction and suggest a model with several pools (insoluble, extracellular soluble, CSF) of Abeta being in partial equilibrium with each other.

Fimbria-fornix lesion does not affect APP levels and amyloid deposition in the hippocampus of APP+PS1 double transgenic mice.

The deposition of amyloid beta peptides (Abeta) and cholinergic dysfunction are two characteristic features of Alzheimer's disease. Several studies have suggested that a compromised cholinergic transmission can increase the amount of amyloid precursor protein (APP) in the denervated cortex (or hippocampus); however, whether this will increase Abeta production is unknown. To investigate the relation between cholinergic neurotransmission and APP metabolism, and the possible role of cholinergic dysfunction in the development of amyloid neuropathology, we lesioned the fimbria-fornix pathway in APP+PS1 double transgenic mice, at 5 and 7 months of age. Three months and 11 months postlesion, the mice were sacrificed for biochemical and histopathological analyses. The fimbria-fornix transection resulted in a substantial depletion of cholinergic markers in the hippocampus at both time points. Three months postlesion, hippocampal APP and Abeta levels were not significantly changed. At 11 months postlesion, the fimbria-fornix lesion did not result in an alteration in either the hippocampal Abeta levels or the extent of Abeta deposition, as assessed by amyloid plaque counts and image analysis of Abeta load in the 18-month-old APP+PS1 mice. Our findings indicate that APP metabolism in mice may be dissociated from cholinergic neurotransmission rather than related as previously suggested in other mammalian species.

Differential diagnosis of Alzheimer disease with cerebrospinal fluid levels of tau protein phosphorylated at threonine 231.

BACKGROUND: Phosphorylation of tau protein at threonine 231 (using full-length tau, 441 amino acids, for the numbering scheme) (p-tau(231)) occurs specifically in postmortem brain tissue of patients with Alzheimer disease (AD) and can be sensitively detected in cerebrospinal fluid (CSF). OBJECTIVES: To determine to what extent CSF levels of p-tau(231) distinguish patients with AD from control subjects and from patients with other dementias, and to investigate whether p-tau(231) levels are a better diagnostic marker than levels of total tau protein (t-tau) in CSF. DESIGN AND SETTING: Cross-sectional, multicenter, memory clinic-based studies. PARTICIPANTS: One hundred ninety-two patients with a clinical diagnosis of AD, frontotemporal dementia (FTD), vascular dementia, Lewy body dementia, or other neurological disorder and healthy controls. MAIN OUTCOME MEASURES: Levels of CSF tau proteins as measured with enzyme-linked immunosorbent assays. RESULTS: Mean CSF levels of p-tau(231) were significantly elevated in the AD group compared with all other groups. Levels of p-tau(231) did not correlate with dementia severity in AD, and discriminated with a sensitivity of 90.2% and a specificity of 80.0% between AD and all non-AD disorders. Moreover, p-tau(231) levels improved diagnostic accuracy compared with t-tau levels when patients with AD were compared with healthy controls (P =.03) and demented subjects (P<.001), particularly those with FTD (P<.001), but not those with vascular and Lewy body dementias. Sensitivity levels between AD and FTD were raised by p-tau(231) compared with t-tau levels from 57.7% to 90.2% at a specificity level of 92.3% for both markers. CONCLUSION: Increased levels of CSF p-tau(231) may be a useful, clinically applicable biological marker for the differential diagnosis of AD, particularly for distinguishing AD from FTD.

Hippocampal A beta 42 levels correlate with spatial memory deficit in APP and PS1 double transgenic mice.

We investigated the role of hippocampal amyloid pathology in spatial learning impairment of a new mouse line carrying mutated human amyloid precursor protein (APP) and presenilin-1 (PS1) transgenes. The APP + PS1 mice were tested in spatial navigation in the water maze and in position discrimination in the T-maze at ages of 3-4 and 11-12 months, before and after the appearance of first amyloid plaques. The APP + PS1 mice were impaired in water maze acquisition and retention only at the age of 11-12 months, but performed equally to controls in the T-maze task at both ages. In the impaired older age group, the levels of total Abeta1-42 in the hippocampus of APP + PS1 mice correlated negatively with the retention score. Here we show for the first time that the age-dependent impairment in memory retention in the traditional water maze of APP + PS1 mice correlates with the amount of total Abeta in hippocampus even at a stage when the amyloid deposits cover less than 1% of the hippocampal volume.