Article

Dementia associated with lacunar infarction

October 1992
Stroke 23(9):1225-9

October 1992
23(9):1225-9

DOI:10.1161/01.STR.23.9.1225

Source
PubMed

Authors:

Chaim Loeb

Northwestern University

The purpose of this study was to assess the number of patients with lacunar lesions who develop dementia and to evaluate in patients with and without dementia the relevance of risk factors for cerebrovascular disease, the occurrence of leukoaraiosis, the volume and location of vascular lesions, the size of ventricular and subarachnoid spaces, and stroke recurrence. One hundred eight patients in whom computed tomograms revealed lacunar lesions that could account for their clinical neurological pictures were followed up for an average of 4 years after their first lacunar stroke. Twenty-five patients (23.1%) developed dementia. The prognosis regarding occurrence of dementia during the follow-up period, evaluated by the Kaplan-Meier method, was significantly worse in subjects with the greatest evidence of cerebral atrophy (p less than 0.009) and in subjects who underwent new focal cerebrovascular episodes (p less than 0.000001). No differences were seen in the frequency of vascular risk factors or the site or volume of lesions between the demented and nondemented groups. Patients with lacunar infarcts suffer from dementia 4-12 times more frequently than the normal population. Cerebral atrophy and recurrent stroke, as well as other as-yet unclarified factors, are involved in producing dementia.

EXPRESS: Predicting post-stroke cognitive impairment using acute CT neuroimaging: A systematic review and meta-analysis

Article

Full-text available

Sep 2021

Background: Identifying whether acute stroke patients are at risk of cognitive decline could improve prognostic discussions and management. Structural computed tomography (CT) neuroimaging is routine in acute stroke, and may, identify those at risk of post-stroke dementia (PSD) or post-stroke cognitive impairment (PSCI). Aim: To systematically review the literature to identify which stroke or pre-stroke features on brain CT scans, performed at the time of stroke, are associated with PSD or PSCI. Summary of review: We searched electronic databases to December 2020. We included studies reporting acute stroke brain CT, and later diagnosis of a cognitive syndrome. We created summary estimates of size of unadjusted association between CT features and cognition. Of 9536 citations, twenty-eight studies (41 papers) were eligible (N=7078, mean age 59.8-78.6 years). Cognitive outcomes were PSD (10 studies), PSCI (17 studies), and one study analysed both. Fifteen studies (N=2952) reported data suitable for meta-analyses. White matter lesions (WML) (6 studies, N=1054, OR=2.46, 95% CI=1.25-4.84), cerebral atrophy (4 studies, N=558, OR=2.80, 95% CI=1.21-6.51), and pre-existing stroke lesions (3 studies, N=352, OR=2.38, 95% CI=1.06-5.32) were associated with PSD. WML (4 studies, N=473, OR=3.46, 95% CI=2.17-5.52) were associated with PSCI. Other CT features were either not associated with cognitive outcome, or there were insufficient data. Conclusions: Cognitive impairment following stroke is of great concern to patients and carers. Features seen on visual assessment of acute stroke CT brain scans are strongly associated with cognitive outcomes. Clinicians should consider when and how this information should be discussed with stroke survivors.

European Stroke Organisation and European Academy of Neurology joint guidelines on post-stroke cognitive impairment

Article

Full-text available

Sep 2021
EUR J NEUROL

Background and purpose The optimal management of post-stroke cognitive impairment (PSCI) remains controversial. These joint European Stroke Organisation (ESO) and European Academy of Neurology (EAN) guidelines provide evidence-based recommendations to assist clinicians in decision making regarding prevention, diagnosis, treatment and prognosis. Methods Guidelines were developed according to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. The working group identified relevant clinical questions, performed systematic reviews, assessed the quality of the available evidence, and made specific recommendations. Expert consensus statements were provided where insufficient evidence was available to provide recommendations. Results There was limited randomized controlled trial (RCT) evidence regarding single or multicomponent interventions to prevent post-stroke cognitive decline. Lifestyle interventions and treating vascular risk factors have many health benefits, but a cognitive effect is not proven. We found no evidence regarding routine cognitive screening following stroke, but recognize the importance of targeted cognitive assessment. We describe the accuracy of various cognitive screening tests, but found no clearly superior approach to testing. There was insufficient evidence to make a recommendation for use of cholinesterase inhibitors, memantine nootropics or cognitive rehabilitation. There was limited evidence on the use of prediction tools for post-stroke cognition. The association between PSCI and acute structural brain imaging features was unclear, although the presence of substantial white matter hyperintensities of presumed vascular origin on brain magnetic resonance imaging may help predict cognitive outcomes. Conclusions These guidelines highlight fundamental areas where robust evidence is lacking. Further definitive RCTs are needed, and we suggest priority areas for future research.

EXPRESS: European Stroke Organisation and European Academy Neurology joint guidelines on post-stroke cognitive impairment

Article

Full-text available

Sep 2021

Introduction: The optimal management of post stroke cognitive impairment remains controversial. These joint European Stroke Organisation (ESO) and European Academy of Neurology (EAN) guidelines provide evidence-based recommendations to assist clinicians in decision making around prevention, diagnosis, treatment, and prognosis. Methods: These guidelines were developed according to ESO standard operating procedure and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. The working group identified relevant clinical questions, performed systematic reviews and, where possible, meta-analyses of the literature, assessed the quality of the available evidence, and made specific recommendations. Expert consensus statements were provided where insufficient evidence was available to provide recommendations based on the GRADE approach. Results: There was limited randomised controlled trial evidence regarding single or multicomponent interventions to prevent post stroke cognitive decline. Interventions to improve lifestyle and treat vascular risk factors may have many health benefits but a beneficial effect on cognition is not proven. We found no evidence around routine cognitive screening following stroke but recognise the importance of targeted cognitive assessment. We described the accuracy of various cognitive screening tests but found no clearly superior approach to testing. There was insufficient evidence to make a recommendation for use of cholinesterase inhibitors, memantine or cognitive rehabilitation for post stroke dementia. We made a weak recommendation against using the nootropics actovegin and cerebrolysin, but quality of evidence was very low. There was limited evidence on the use of prediction tools for post stroke cognitive syndromes (cognitive impairment, dementia and delirium). The association between post stroke cognitive impairment and most acute structural brain imaging features was unclear. Conclusions: These guidelines have highlighted fundamental areas where robust evidence is lacking. Further randomised controlled trials are needed and we suggest priority areas for future research.

Study of clinical risk factors and predictors of post stroke vascular cognitive impairment

Article

Mar 2018

Introduction: Cognitive impairment due to cerebro vascular disease is termed” vascular cognitive Impairment “(VCI) and forms a spectrum that includes vascular dementia and milder forms of cognitive impairment. Vascular cognitive impairment has some varied and diverse aetiology. This is particularly important as apart from age vascular risk factors, are the most important and presently the only treatable precursor to dementia. This prospective observational study was carried out in indept. Of medicine, GMC Bhopal. Methods: A standard protocol was applied at admission and 3 months after stroke, this protocol included clinical, functional and cognitive assessments, various lab tests and MMSE. Results: Amongst the various risk factors hypertension, diabetes mellitus, prior stroke, dyslipidemia, ischemic heart disease, tobacco chewing, smoking, family history of dementia was more frequently seen in vascular cognitive impairment group. In this study, the frequency of patients having post stroke vascular cognitive impairment (VCI)is 54%. 18%of the patients had VaD (Vascular dementia), 36% of the patients had VMCI(vascular mild cognitive impairment), 46% of the patients had NO VCI (no vascular cognitive impairment. There was significant association of risk factors like Hypertension (p=0.022) diabetes mellitus (P=0.038), dyslipidaemia (p=0.034), prior stroke(p=0.046) with development of vascular cognitive impairment. Post stroke dementia has considerable morbidity. Conclusion: The predictors of development of Vascular cognitive impairment following stroke in this study are lower educational status, Hypertension, Diabetes mellitus, Dyslipidemia, Prior stroke, urinary incontinence, High sys. BP, NIHSS score, LDL level, abnormal ECG, Strategic site lesion and greater severity of age related white matter changes.

Biological and imaging predictors of cognitive impairment after stroke: a systematic review

Article

Full-text available

Nov 2019
J NEUROL

Background Cognitive impairment is frequent after stroke, and several studies have suggested that biological and imaging characteristics present before stroke are associated with the development of post-stroke cognitive impairment. Objective The aim of our study was to systematically review biological and imaging predictors of cognitive impairment after stroke. Method Studies were identified from bibliographic databases and reference lists, and were included if conducted in patients with acute stroke, with at least 30 patients, and a follow-up of at least 3 months. We included articles on potential biomarkers of cognitive impairment that pre-existed to stroke. Results We identified 22,169 articles, including 20,349 with abstract. After analysis, 66 studies conducted in 42 cohorts met selection criteria. They included 30–9522 patients [median 170; interquartile range (IQR) 104–251] with a median follow-up of 12 months (IQR 3–36). All studies met quality criteria for description of the study population and standardization of biomarkers. Twenty-nine studies met all quality criteria. There was no convincing evidence that any biological marker may predict cognitive impairment. The most consistent predictors of cognitive impairment after stroke were global atrophy and medial temporal lobe atrophy. Conclusion Pre-existing cerebral atrophy is the most consistent predictor of cognitive impairment that can be identified in patients with an acute stroke.

Prefrontal Cortex Stroke Induces Delayed Impairment in Spatial Memory

Article

Aug 2015

Stroke is the leading cause of long-term disability. Little is known about the effects of stroke on cognitive deficits. The subtle nature of cognition and its respective domains in areas such as working memory and attention can make this difficult to diagnose and treat. We aimed to establish a model of focal ischemia that targets the prefrontal cortex (PFC) and induce memory impairments. Stroke and sham mice were assessed at one and four-weeks post-stroke on various tests: open-field task to assess activity; grid-walk and cylinder task to assess motor impairments; elevated plus maze to assess anxiety; novel-object and object-location recognition tasks to assess memory impairment. Stroke mice in the open-field showed a small increase in activity with no effects on gross motor tasks or anxiety levels (P ≥ 0.05) at one and four-weeks post-stroke. Assessment of stroke mice on the novel object task showed no differences at either one or four-weeks compared to sham mice (P ≥ 0.05). However, assessment of stroke mice on the object-location recognition task revealed a significant (P ≤ 0.05) impairment in spatial memory by four-weeks compared to controls. Further, we show that stroke results a small decrease in volume of the medial dorsal nucleus of the thalamus (P ≤ 0.05). This is the first evidence that demonstrates stroke to the PFC results in delayed onset impairment in spatial memory, similar to findings in human epidemiological data. We suggest that this model may be a useful tool in assessing potential rehabilitative/cognitive therapies after stroke. Copyright © 2015. Published by Elsevier B.V.

Accepted Article European Stroke Organisation (ESO) and European Academy Neurology (EAN) Joint Guidelines on Post Stroke Cognitive Impairment

Preprint

Full-text available

Sep 2021

Introduction The optimal management of post stroke cognitive impairment remains controversial. These joint European Stroke Organisation (ESO) and European Academy of Neurology (EAN) guidelines provide evidence-based recommendations to assist clinicians in decision making around prevention, diagnosis, treatment, and prognosis. Methods Guidelines were developed according to the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. The working group identified relevant clinical questions, performed systematic reviews, assessed the quality of the available evidence, and made specific recommendations. Expert consensus statements were provided where insufficient evidence was available to provide recommendations. Results There was limited randomised controlled trial evidence regarding single or multicomponent interventions to prevent post stroke cognitive decline. Lifestyle interventions and treating vascular risk factors have many health benefits but a cognitive effect is not proven. We found no evidence around routine cognitive screening following stroke but recognise the importance of targeted cognitive assessment. We described the accuracy of various cognitive screening tests but found no clearly superior approach to testing. There was insufficient evidence to make a recommendation for use of cholinesterase inhibitors, memantine nootropics or cognitive rehabilitation. There was limited evidence on the use of prediction tools for post stroke cognition. The association between post stroke cognitive impairment and acute structural brain imaging features was unclear, although the presence of substantial white matter hyperintensities of presumed vascular origin on MRI brain may help predict cognitive outcomes. Conclusions These guidelines highlight fundamental areas where robust evidence is lacking. Further, definitive randomised controlled trials are needed, and we suggest priority areas for future research.

An Overview of Alzheimer's Disease

Chapter

Full-text available

Feb 2021

Alzheimer`s disease (AD) is the most common and incurable form of dementia. The present AD treatments produce only an uncertain amelioration of symptoms. Research on AD has particularly focused on the central nervous system. Though, some systemic and peripheral abnormalities are now clearly understood that are associated to AD. Current research on these alterations that leads to AD are becoming further defined more evidently. Two microscopic features contribute for the depiction of the disease, the amyloid plaques and neurofibrillary tangles. All these aspects are accountable for the deliberate and gradual weakening of memory that disturb the cognitive control, language, thinking and personality. For the diagnosis of AD, some neuropsychological tests are being performed in various spheres of cognitive functions. To date, cholinesterase inhibitors are used as a drug for the treatment of AD, because these are the individual drugs that have depicted substantial enhancements in the cognitive functions of AD patients. Despite the efficacy of cholinesterase inhibitors, the degeneration of neurons is continuing even while being treated an AD patient. For this cause, further biochemical pathways related to pathophysiology of AD have been revealed as an alternative for the treatment of these conditions such as hindrance of glycogen synthase kinase-3β and β-secretase. The present chapter aims to conduct a review of the pathophysiology, symptoms, epidemiology, analysis and treatment of AD.

Stroke Recurrence Rate and Risk Factors Among Stroke Survivors in Sub-Saharan Africa: A Systematic Review

Article

Full-text available

Apr 2024

Purpose Evidence supporting secondary stroke in sub-Saharan Africa is scarce. This study describes the incidence of stroke recurrence and associated risk factors in sub-Saharan Africa. Methods and Materials Scientific databases were systematically searched from January 2000 to December 2022 for population-based observational studies, case-control or cohort studies of recurrent stroke involving adults aged 18 years and above in sub-Saharan Africa (SSA). We assessed the quality of the eligible studies using the Critical Appraisal Skills Program (CASP) checklist for observational studies. Results Six studies met the inclusion criteria and were included in this study. Stroke recurrence rates in SSA ranged from 9.4% to 25%. Majority of the studies were conducted from Western Africa and showed that stroke recurrence rates are high within sub-Saharan Africa ranging from 2% to 25%. The known stroke risk factors such as hypertension, chronic alcohol consumption, etc., remained the leading causes of stroke recurrence. The studies reported a higher mortality rate ranging from 20.5 −23% among those with recurrent strokes compared to primary strokes. Conclusion This systematic review is an update and summary of the available literature on stroke recurrence within sub-Saharan Africa. Further studies are warranted to assess the outcomes and burden of stroke recurrence in SSA.

Correlations between cognitive function and gray matter alterations in patients with acute lacunar stroke

Article

Full-text available

Jun 2021

Karen M. von Deneen

Researchers emphasized acute lacunar stroke (ALS) patients suffer from poor social/physical outcomes, cognitive decline, and decreased quality of life. We hypothesized brain abnormalities may occur in ALS during this particular stage and may be associated with cognitive deficits upon evaluation. We investigated structural abnormalities in ALS using magnetic resonance imaging and voxel-based morphometry conducted on 28 healthy controls (HC) and 29 patients with ALS and proximal anterior circulation occlusion within 12 hours of symptom onset. Mini-Mental State Examination (MMSE) scores were used to evaluate cognitive dysfunction. Decreased gray matter (GM) in ALS vs. HC was predominantly in the superior frontal gyrus, inferior frontal gyrus, insula, superior temporal gyrus (STG), heschl gyrus, middle temporal gyrus (MTG), posterior cingulate cortex (PCC), hippocampus (HIP), and others. Positive correlation was found between GM density and MMSE scores in STG ( r = 0.59, p = 0.0007), MTG ( r = 0.46, p = 0.01), PCC ( r = 0.42, p = 0.02), HIP ( r = 0.4, p = 0.03), and medial prefrontal cortex ( r = 0.5, p = 0.005). This study provided further information on pathophysiological/morphological mechanisms related to cognitive impairment in ALS and is the basis for further studies in aging-related diseases.

Connecting vascular aging and frailty in Alzheimer’s Disease

Article

Feb 2021
MECH AGEING DEV

Aging plays an important role in the etiology of the most common age-related diseases (ARDs), including Alzheimer’s disease (AD). The increasing number of AD patients and the lack of disease-modifying drugs warranted intensive research to tackle the pathophysiological mechanisms underpinning AD development. Vascular aging/dysfunction is a common feature of almost all ARDs, including cardiovascular (CV) diseases, diabetes and AD. To this regard, interventions aimed at modifying CV outcomes are under extensive investigation for their pleiotropic role in ameliorating and slowing down cognitive impairment in middle-life and elderly individuals. Evidence from observational and clinical studies confirm the notion that the earlier the interventions are conducted, the most favorable are the effects on cognitive function. Therefore, epidemiological research should focus on the early detection of deviations from a healthy cognitive aging trajectory, through the stratification of adult individuals according to the rate of aging. Here, we review the interplay between vascular and cognitive dysfunctions associated with aging, to disentangle the complex mechanisms underpinning the development and progression of neurodegenerative disorders, with a specific focus on AD.

Frontal Cortex Stroke-induced Impairment in Spatial Working Memory on the Trial-unique Nonmatching-to-location Task in Mice

Article

Dec 2020
NEUROBIOL LEARN MEM

Stroke-induced cognitive impairments are of significant concern, however mechanisms that underpin these impairments remain poorly understood and researched. To further characterise cognitive impairments in our frontal cortex stroke model, and to align our assessments with what is used clinically, we tested young C57BL/6J mice trained in operant touchscreen chambers to complete the trial-unique nonmatched-to-location (TUNL) task. Based on baseline performance, animals were given either stroke (n = 12) or sham (n = 12) surgery using a photothrombosis model, bilaterally targeting the frontal cortex. Upon recovery, post-stroke spatial working memory was assessed by varying the degree of separation and delay within TUNL trials. Seven weeks after surgery, animals received a prelimbic injection of the retrograde tracer cholera toxin B (CTB) to access thalamo-PFC connectivity. Tissue was then processed histologically and immunohistochemically to assess infarct volume, astrogliosis and thalamocortical connectivity. Assessment of TUNL probes revealed sensitivity to a frontal cortex stroke (separation: p = 0.0003, delay: p < 0.0001), with stroke animals taking significantly longer (p = 0.0170) during reacquisition of the TUNL task, relative to shams. CTB-positive cell counts revealed a stroke-induced loss of thalamo-PFC connectivity. In addition, quantification of reactive astrogliosis revealed a positive correlation between the degree of astrogliosis expanding into white matter tracts and the development of cognitive impairments. This study reveals a stroke-induced impairment in mice completing the TUNL task. Our findings also demonstrate a significant loss of thalamo-PFC connections and a correlation between white matter reactive astrogliosis and cognitive impairment. Future experiments will investigate therapeutic interventions in the hope of promoting functional improvement in cognition.

Is it possible to prevent cerebral embolization by improving the design and technology of carotid stent implantation?

Article

Full-text available

Oct 2020
Expet Rev Cardiovasc Ther

Introduction: The prevention of atherosclerotic plaque fragmentation during carotid artery stenting is a fundamental problem in decreasing the risk of disability of patients. The goal of this review is to clarify whether the stent design can have a decisive impact on the rate of intraoperative and postoperative complications. Areas covered: Different designs of the carotid stents are briefed and the advantages and disadvantages of different stent designs are discussed as well as the results of their clinical use. Various solutions are presented to reduce cerebral embolism during carotid artery stenting. Expert opinion: There is no conclusive evidence for the benefits of closed cell and hybrid stents. The stent design cannot completely resolve the problem of cerebral embolism. Most of the events of cerebral microembolism occur at the stages of stent delivery rather than protrusion of an atherosclerotic plaque in the long-term follow-up. Most likely, minimization of the risks for periprocedural and postprocedural strokes requires not only the new solutions in stent design as well as the corresponding delivery systems and brain embolic protection systems, but also the new strategies of preprocedural drug stabilization of the atherosclerotic plaque in the carotid artery. Abbreviations: CAS, carotid artery stenting; CE, carotid endarterectomy; DW-MRI, diffusion-weighted magnetic resonance imaging; ECA, external carotid artery; ICA, internal carotid artery; IVUS, intravascular ultrasound examination; OCT, optical coherence tomography.

Prevalence of Dementia and Cognitive Impairment after Stroke: An Epidemiological Study

Article

Jan 2018

Effect of aerobic training on vascular and metabolic risk factors for recurrent stroke: a meta-analysis

Article

Full-text available

Dec 2019

AIM: This meta-analysis aimed to determine the effect of aerobic training, compared to non-aerobic interventions , on vascular and metabolic risk factors for recurrent stroke. METHOD: This study was conducted using the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines (PRISMA). Searches were performed in PubMed, Embase, Cochrane library and Cinahl up to May 8 th 2019. Randomized clinical trials evaluating the effect of solely aerobic training on vascular and metabolic risk factors for recurrent stroke were included in a meta-analysis if relevant outcomes were reported in at least two articles. RESULTS: Our search resulted in a total of 7381 hits. Eleven outcomes out of nine articles were included in the meta-analysis. A significant positive effect of aerobic training was found on systolic blood pressure (-3.59 mmHg, 95% CI -6.14 to -1.05) and fasting glucose (-0.12 mmol/l, 95% CI -0.23 to -0.02). The effect on systolic blood pressure further improved when only high-quality studies were included (-4.95 mmHg, 95% CI -8.24 to -1.66). CONCLUSION: Aerobic training results in a significant positive effect on systolic blood pressure and fasting glucose after stroke when compared to non-aerobic usual care or non-aerobic exercise.

Cognitive features of white matter lesions accompanied by different risk factors of cerebrovascular diseases

Article

Nov 2019

Background: The relationship between different risk factors and the cognitive impairment of white matter lesions (WML) remains poorly understood. Objectives: To investigate the features of cognitive impairment of patients diagnosed with WML accompanied by different risk factors of cerebrovascular diseases. Material and methods: A total of 157 cases of WML patients were divided into no risk factor group (n = 26), hypertension group (n = 35), diabetes mellitus group (n = 27), dyslipidemia group (n = 30), and mixed factors group (n = 39). Results: The severity of WML (Fazekas score) in the hypertension and mixed factors groups was higher than in the non-risk factors group. The Montreal Cognitive Assessment (MoCA) scores in the hypertension and mixed factors groups were lower than in the non-risk factors group. The scores of MoCA, immediate memory and delayed recall in the hypertension and mixed factors groups with Fazekas score ≥3 were lower than in the peer group with Fazekas score <3. The scores of MoCA and immediate memory in the hypertension and mixed factors groups with Fazekas score ≥3 were lower than in the non-risk factors group with Fazekas score ≥3. Conclusions: Hypertension aggravates the severity of WML and cognitive impairment. The severity of WML is positively correlated with the severity of cognitive impairment accompanied by these risk factors.

Altered Hippocampal–Prefrontal Dynamics Following Medial Prefrontal Stroke in Mouse

Article

Full-text available

Dec 2019

Frontal infarcts can produce cognitive impairments that affect an individual’s ability to function in everyday life. However, the precise types of deficits, and their underlying mechanisms, are not well-understood. Here we used a prefrontal photothrombotic stroke model in C57BL/6J mice to characterise specific cognitive changes that occur in the 6 weeks post-stroke. Behavioural experiments were paired with in vivo electrophysiology to assess whether changes in oscillatory communication between the prefrontal cortex (PFC) and the hippocampus (HPC) mirrored any observed behavioural changes. We found that mice in the stroke group exhibited a delayed onset impairment in tasks of spatial working memory (object location recognition and Y-maze) and that this correlated with reduced PFC–HPC theta band coherence (5–12 Hz) during the task. In the open field, mice in the stroke group exhibited hyperactivity as compared to controls, and stroke animals also exhibited significantly higher beta band activity (13–30 Hz) in the PFC and the HPC. Taken together our results suggest that infarcts in the PFC result in PFC–HPC oscillatory communication changes in the theta and beta bands, correlating with altered performance in spatial memory and open field tasks respectively. Of particular interest, early open field changes in PFC beta band power post-stroke correlated to later-stage spatial memory impairments, highlighting this as a potential biomarker for detecting when spatial memory impairments are likely to occur.

Stroke Induces a BDNF-Dependent Improvement in Cognitive Flexibility in Aged Mice

Article

Full-text available

May 2019
Neural Plast

Stroke remains a leading cause of disability worldwide. Recently, we have established an animal model of stroke that results in delayed impairment in spatial memory, allowing us to better investigate cognitive deficits. Young and aged brains show different recovery profiles after stroke; therefore, we assessed aged-related differences in poststroke cognition. As neurotrophic support diminishes with age, we also investigated the involvement of brain-derived neurotrophic factor (BDNF) in these differences. Young (3-6 months old) and aged (16-21 months old) mice were trained in operant touchscreen chambers to complete a visual pairwise discrimination (VD) task. Stroke or sham surgery was induced using the photothrombotic model to induce a bilateral prefrontal cortex stroke. Five days poststroke, an additional cohort of aged stroke animals were treated with intracerebral hydrogels loaded with the BDNF decoy, TrkB-Fc. Following treatment, animals underwent the reversal and rereversal task to identify stroke-induced cognitive deficits at days 17 and 37 poststroke, respectively. Assessment of sham animals using Cox regression and log-rank analyses showed aged mice exhibit an increased impairment on VD reversal and rereversal learning compared to young controls. Stroke to young mice revealed no impairment on either task. In contrast, stroke to aged mice facilitated a significant improvement in reversal learning, which was dampened in the presence of the BDNF decoy, TrkB-Fc. In addition, aged stroke control animals required significantly less consecutive days and correction trials to master the reversal task, relative to aged shams, an effect dampened by TrkB-Fc. Our findings support age-related differences in recovery of cognitive function after stroke. Interestingly, aged stroke animals outperformed their sham counterparts, suggesting reopening of a critical window for recovery that is being mediated by BDNF.

Small Vessel Disease on Neuroimaging in a 75-Year-Old Cohort (PIVUS): Comparison With Cognitive and Executive Tests

Article

Full-text available

Jul 2018

Background and Purpose: Signs of small vessel disease (SVD) are commonly seen on magnetic resonance imaging (MRI) of the brain in cognitively healthy elderly individuals, and the clinical relevance of these are often unclear. We have previously described three different MRI manifestations of SVD as well as cerebral perfusion in a longitudinal study of non-demented 75-year-old subjects. The purpose of the present study was to evaluate the relationship of these findings to cognition and executive function at age 75 and changes after 5 years. Methods: In all, 406 subjects from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study were examined with MRI of the brain at age 75 years. Two-hundred and fifty of the subjects were re-examined 5 years later. White matter hyperintensities (WMHs) and lacunar infarcts (LIs) were assessed on both occasions, but microbleeds (MBs) and perfusion only at age 75. Cognitive function was screened by the Mini Mental State Examination (MMSE). Trail Making Test A and B (TMT-A and TMT-B) were performed at baseline and at follow-up at age 80. Results: At baseline, 93% performed >27 points in the MMSE. The TMT-B at age 75 was significantly related to WMH visual scoring after adjustment for sex, education and cerebrovascular disease risk factors (+80 s (95% CI 0.3–161 s), P < 0.05 for grade 2–3 vs. grade 0). Neither MMSE nor TMT-A was significantly related to WMH scoring. There was no relation between any test performance and WMH volume, white matter volume, number of MBs or brain perfusion at age 75. Subjects who had sustained a new LI (n = 26) showed a greater increase of the time to perform TMT-A at the 5-year follow-up (+25 s vs. +4 s in LI-free subjects, P = 0.003). Changes in MMSE or TMT-A and -B test performance between ages 75 and 80 were not related to changes in WMH scoring or volume during the 5 years follow-up, or to brain perfusion at age 75. Conclusion: In this cognitively healthy community-based population, moderate-severe WMHs and incident LIs on brain MRI in individuals aged 75–80 years were associated with a mild impairment of processing speed and executive function.

Modifying progression of aging and reducing the risk of neurodegenerative diseases by probiotics and synbiotics

Article

Mar 2018
Front Biosci

Aging, which affects most of the multi-cellular organisms, is due to a potentially complex set of mechanisms that collectively cause a time-dependent decline of physiological functions. Aging restrains longevity and leads to neurodegenerative diseases including dementia, Alzheimer's disease and lacunar stroke. Human microbiota is now considered to have a strong impact on the progression of aging. The impact of aging and the risk of neurodegenerative diseases can be reduced by using probiotics, or preferably by combining probiotics and prebiotics, also known as synbiotics, that can drastically modify the composition of gut microbiome.

Modifications of tau protein after cerebral ischemia and reperfusion in rats are similar to those occurring in Alzheimer’s disease – Hyperphosphorylation and cleavage of 4- and 3-repeat tau

Article

Full-text available

Sep 2016

Epidemiological studies have suggested a close relationship between cerebral ischemia and Alzheimer’s disease (AD). To clarify the pathological association of tau dynamics in both diseases, we performed comprehensive studies on the posttranslational modification of tau in cerebral ischemia and reperfusion (I/R) in rats. The present study suggests that both 4-repeat and 3-repeat tau isoforms are hyperphosphorylated in cerebral I/R, similar to the case in AD. The generation of a 60-kDa Asp⁴²¹-truncated tau in cerebral I/R preceded the emergence of a 17-kDa 3-repeat tau fragment and a 25-kDa 4-repeat tau fragment. The regional redistribution of tau from the neuropil to neuronal perikarya in our stroke model is thought to share similarity with that occurring in AD. In addition, immunofluorescence staining revealed the formation of axonal varicosities in cerebral I/R. Altered tau distribution may influence microtubule stability, disturbances in axonal transport, and the resulting formation of axonal varicosities. The staining profiles of granules in the ischemic cortex that were immunopositive for RD3, RD4, and AT8 in neuronal perikarya and that were argyrophilic on Gallyas-Braak staining were similar to those in AD. These findings suggest that transient cerebral ischemia shares a common pathology with AD, in the modification of tau protein.

Targeting CDK5 post-stroke provides long-term neuroprotection and rescues synaptic plasticity

Article

Full-text available

Aug 2016

Post-stroke cognitive impairment is a major cause of long-term neurological disability. The prevalence of post-stroke cognitive deficits varies between 20% and 80% depending on brain region, country, and diagnostic criteria. The biochemical mechanisms underlying post-stroke cognitive impairment are not known in detail. Cyclin-dependent kinase 5 is involved in neurodegeneration, and its dysregulation contributes to cognitive disorders and dementia. Here, we administered cyclin-dependent kinase 5-targeting gene therapy to the right hippocampus of ischemic rats after transient right middle cerebral artery occlusion. Cyclin-dependent kinase 5 RNA interference prevented the impairment of reversal learning four months after ischemia as well as neuronal loss, tauopathy, and microglial hyperreactivity. Additionally, cyclin-dependent kinase 5 silencing increased the expression of brain-derived neurotrophic factor in the hippocampus. Furthermore, deficits in hippocampal long-term potentiation produced by excitotoxic stimulation were rescued by pharmacological blockade of cyclin-dependent kinase 5. This recovery was blocked by inhibition of the TRKB receptor. In summary, these findings demonstrate the beneficial impact of cyclin-dependent kinase 5 reduction in preventing long-term post-ischemic neurodegeneration and cognitive impairment as well as the role of brain-derived neurotrophic factor/TRKB in the maintenance of normal synaptic plasticity.

Characteristics of dynamic cerebral autoregulation in cerebral small vessel disease: Diffuse and sustained

Article

Full-text available

Oct 2015

Cerebral small vessel disease is a major cause of stroke and vascular dementia; however, the pathogenesis is largely unclear. In this study, we investigated the characteristics of the impairment of dynamic cerebral autoregulation (dCA) in lacunar infarction patients. Seventy-one lacunar infarction patients were enrolled in the study, including 46 unilateral middle cerebral artery (MCA) territory stroke patients and 25 unilateral posterior cerebral artery (PCA) territory stroke patients. Each group of patients was randomly divided into two subgroups. Group 1 underwent dCA assessments in the bilateral MCAs, and Group 2 underwent dCA assessments in the bilateral PCAs. All patients were followed up for 6 months. Transfer function analysis was applied to derive the autoregulatory parameters of gain and phase difference. In the unilateral MCA territory stroke patients, impairments of dCA were observed in both the MCAs and PCAs, and the same results were observed in the unilateral PCA territory stroke patients. These impairments remained unchanged during the 6-month follow-up. In lacunar infarction, which is most prevalent type of cerebral small vessel disease, though patients with unilateral MCA territory/PCA territory stroke, the impairments of dCA were global and sustained. This finding suggests that the physiological changes associated with lacunar infarction were diffuse.

Characterizing brain iron deposition in subcortical ischemic vascular dementia using susceptibility-weighted imaging: An in vivo MR study

Article

Full-text available

Apr 2015

Stroke and cognitive disorders

Article

Jun 2011

Cognitive disorders (CDs) are diagnosed in most patients within the first months after stroke. Moreover, the prevalence of poststroke dementia, the most severe type of CDs, is 7-40% in relation to patient age and prior stroke severity. The major risk factors of poststroke CDs are elderly age, recurrent stroke, low education level, pronounced leukoareosis, and/or hippocampal atrophy, as evidenced by magnetic resonance imaging (MRI), and left-hemisphere stroke. Prestroke CDs is an important predictor of poststroke dementia that is commonly detected retrospectively during the directed interview of relatives. This fact suggests that stroke is not the only cause of CDs, but frequently decompensates or engages a physician's attention to already existing CDs. Three clinical and pathogenetic types of poststroke CDs may be identified. These include sequels of strategic infarction crucial for cognitive functions; poststroke vascular CSs associated with reinfarctions and/or leukoareosis; and mixed (vascular and degenerative) CDs caused by a decompensated latent degenerative process. Approaches to managing poststroke CDs are the same as those in CDs as a whole. The study of the preventive effect of neuroprotective agents against the development of poststroke CDs and dementia in the rehabilitative period of stroke is promising.

Poststroke cognitive impairments and their therapy with ceraxon

Article

Sep 2011

Objective: to evaluate the effect of citicoline (ceraxon) on recovery of cognitive functions in patients after ischemic stroke. Subjects and methods. Thirty-three patients (13 males and 20 women) aged 46-82 years (mean age 66.5±6.75 years) after ischemic stroke were examined 3 months to 1 year after its development. Neuropsychological examination showed that all the patients had mild or moderate cognitive impairments as disorders of memory, attention, and thinking. Results and discussion. Ten-day treatment with citicoline (ceraxon) in a dose of 500 or 1000 mg/day caused positive changes in the neurody-namic characteristics of cognitive functions, and improvements in memory, thinking, and health in the patients. Cognitive improvement was more significant when ceraxon was used in a dose of 1000 mg/day.

P25/CDK5-mediated Tau Hyperphosphorylation in Both Ipsilateral and Contralateral Cerebra Contributes to Cognitive Deficits in Post-stroke Mice

Article

Nov 2023

Post-stroke cognitive impairment (PSCI) develops in approximately one-third of stroke survivors and is associated with ingravescence. Nonetheless, the biochemical mechanisms underlying PSCI remain unclear. The study aimed to establish an ischemic mouse model by means of transient unilateral middle cerebral artery occlusions (MCAOs) and to explore the biochemical mechanisms of p25/cyclin-dependent kinase 5 (CDK5)-mediated tau hyperphosphorylation on the PSCI behavior. Cognitive behavior was investigated, followed by the detection of tau hyperphosphorylation, mobilization, activation of kinases and/or inhibition of phosphatases in the lateral and contralateral cerebrum of mice following ischemia in MACO mice. Finally, we treated HEK293/tau cells with oxygen-glucose deprivation (OGD) and a CDK5 inhibitor (Roscovitine) or a GSK3β inhibitor (LiCl) to the roles of CDK5 and GSK3β in mediating ischemia-reperfusion-induced tau phosphorylation. Ischemia induced cognitive impairments within 2 months, as well as causing tau hyperphosphorylation and its localization to neuronal somata in both ipsilateral and contralateral cerebra. Furthermore, p25 that promotes CDK5 hyperactivation had significantly higher expression in the mice with MCAO than in the shamoperation (control) group, while the expression levels of protein phosphatase 2 (PP2A) and the phosphorylation level at Tyr307 were comparable between the two groups. In addition, the CDK5 inhibitor rescued tau from hyperphosphorylation induced by OGD. These findings demonstrate that upregulation of CDK5 mediates tau hyperphosphorylation and localization in both ipsilateral and contralateral cerebra, contributing to the pathogenesis of PSCI.

Recovery from Cognitive and Behavioral De.cits

Chapter

Jun 2002

Association of blood lipids, atherosclerosis and statin use with dementia and cognitive impairment after stroke: A systematic review and meta-analysis

Article

Sep 2019
AGEING RES REV

Vascular cognitive impairment: diagnosis and treatment

Article

Jan 2015

Role of Cerebrovascular Disease in Cognition

Chapter

Mar 2018

Ana Verdelho

Vascular risk factors and cerebrovascular disease are recognized factors implicated in the evolution towards dementia, not only of vascular origin, but also of degenerative dementia as Alzheimer’s disease. Even among nondemented subjects, hypertension, diabetes, and stroke are associated with worse performance in attention, speed and motor control, and executive functions. Influence of vascular risk factors in cognition starts early in life. Recently, several publications expressed that intervention in potential modifiable risk factors should receive special attention in order to delay or prevent dementia. Current scientific evidence sustains that policy actions should be conducted in order to reduce vascular risk factors in middle life, with population and community-level measures. Cerebral small vessel disease, which can be expressed by white matter changes, lacunes, and microbleeds, has gained clinical relevance in the last decades. Intervention in prevention of this previously overlooked disease can represent a potential outcome in experimental studies aiming to reduce cerebrovascular burden.

Demenz

Chapter

Jan 2017

Die vorliegende Übersicht zu den Demenzerkrankungen versucht, klinisch besonders relevante Aspekte von Diagnostik und Therapie in den Vordergrund zu stellen, dabei aber gleichzeitig wichtige molekular-pathophysiologische Grundlagen zu vermitteln, die vielfach für das tiefere Verständnis diagnostischer Verfahren und therapeutischer Behandlungsansätze unverzichtbar sind. Dabei werden aktuelle Entwicklungen in Diagnostik und Therapie berücksichtigt, aber es wird mit Bezug auf die aktualisierten S3-Leitlinien „Demenzen“ (Langversion, Januar 2016) differenziert, ob diese bereits Eingang in die klinische Praxis genommen haben oder sich noch in der Phase der Validierung befinden. Die vorliegende Übersicht macht deutlich, dass Demenz bei mehr als 70 Demenzerkrankungen ein ausgesprochen heterogenes Syndrom ist, wobei zwischen primär degenerativen und den zu einem geringen Anteil sekundären Demenzen unterschieden werden kann. Neben der bisher weiltweit weiter verbindlichen ICD-10-Klassifikation stellen wir auch die konzeptionell tiefgreifend modifizierte neue DSM-5-Klassifikation neurokognitiver Störungen vor, die den klassischen Demenzbegriff auflöst. Weiterhin macht die aktuelle klinische Forschung und internationale Leitlinienentwicklung deutlich, dass diagnostische Biomarker für eine „State of the art“ Früh- und Differenzialdiagnostik demenzieller Erkrankungen auch für die klinische Praxis einen wichtigen Beitrag leisten. Biomarkergestützt konnte zwischenzeitlich auch eine molekular-prädiktive Diagnostik der drohenden Demenz etabliert werden, die zwar für die klinische Praxis zur Zeit noch keinen hohen Stellenwert einnimmt, aber innerhalb der klinischen Therapieforschung zu dringend benötigten ersten präventiven Behandlungsansätzen bereits unverzichtbar geworden ist. In diesem Zusammenhang werden auch neuere diagnostische Klassifikationen vorgestellt, die zwar noch nicht Eingang in die ICD-10 genommen haben, aber bereits international validiert wurden und bereits für zulassungsrelevante Medikamentenstudien eingesetzt werden. In kaum einem anderen Bereich der Psychiatrie hat die biomarkerunterstützte Diagnostik einen so hohen Stellenwert eingenommen wie im Bereich demenzieller Erkrankungen und hier zeichnet sich ab, dass über diesem Ansatz neue Subphänotypen von Demenzerkrankungen beschrieben werden können, die wahrscheinlich zukünftig auch für subphänotypspezifische Therapieansätze relevant werden.

Cerebrovascular Diseases

Chapter

Jan 2002

Michael Daffertshofer

Stroke is the third leading cause of death in the western world. Each year, approximately 500,000 people in the United States experience a stroke; for 150,000 of them the outcome is fatal. The US National Health Interview Survey indicates that the prevalence of stroke in the United States is 720/100,000 among the white population and 910/100,000 in the nonwhite population [1].

Demenz

Chapter

Nov 2016

Demenz

Chapter

Jan 2003

Demenz

Chapter

Jan 2011

Das Demenzsyndrom ist durch die progrediente Entwicklung vielfältiger kognitiver und psychopathologischer Defizite charakterisiert, wobei neben einer Merkfähigkeits - und Gedächtnisstörung weitere kognitive Einbußen (»Werkzeugstörungen «) vorhanden sein müssen: Hierzu zählen z. B. Orien tierungs-, Aufmerksamkeits- und Konzentrationsstörungen, Aphasie, Apraxie, Agnosie, Alexie, Akalkulie, Visuo - konstruktion oder eine Beeinträchtigung der Exekutivfunktionen (Planen, Organi sieren, Abstrahieren). Im Vergleich zur noch z. T. verbreiteten deutschsprachigen Tradition, in der der Demenzbegriff ausschließlich auf schwere fortgeschrittene Zustände intellektuellen Abbaus angewendet wurde, ist die moderne Definition erheblich weiter gefasst (American Psychiatric Association 1994). Die Störung kann reversibel oder irreversibel sein, muss aber das Gedächtnis betreffen und darf nicht mit einer qualitativen Bewusstseinsstörung einhergehen. Das Ausmaß der kognitiven Defizite muss zu einer individuell bedeutsamen Beeinträchtigung der Alltagsbewältigung führen und eine Verschlechterung gegenüber einem zuvor höheren Leistungsniveau darstellen.

Organische psychische Störungen

Chapter

Jan 2002

Tilman Wetterling

Das Spektrum der organischen psychischen Störungen umfasst eine Vielzahl von verschiedenen Störungen. Diese werden in den folgenden Kapiteln eingehend dargestellt.

Erkrankungen, die zu einer organischen psychischen Störung führen können

Chapter

Jan 2002

Tilman Wetterling

In diesem Kapitel werden Erkrankungen, die häufig zu einer organisch bedingten psychischen Störung führen können, ausführlich dargestellt. Dabei wird auch darauf eingegangen, ob und inwieweit psychische Symptome Frühsymptome oder gar die Erstmanifestation dieser Erkrankungen sein können. Da bei einer Reihe der in Frage kommenden Störungen verschiedene OPS auftreten können und daher die Differenzialdiagnose erschwert ist, sind in einer tabellarischen Übersicht (Tabelle 5.1) die am häufigsten vorkommenden zusammengestellt.

Use of Estrogens as Neuroprotectants in Stroke and Alzheimer’s Disease

Chapter

Apr 2005

Vascular Cognitive Impairment and Dementia

Article

Jun 2004
NEUROBIOL AGING

Timo Erkinjuntti

Vascular dementias (VaDs) are the second most common cause of dementia. 1 2 3 4 5 Cerebrovascular disease (CVD) relates also to a high risk of cognitive impairment and dementia. 6 7 In addition, vascular factors such as coexisting stroke and white matter lesions (WMLs) relate to Alzheimer's disease (AD). 8 Thus, vascular causes are an important factor in cognitive impairment worldwide. 9

Cognitive consequences of cerebral small vessel disease

Article

Jan 2011

Cognitive implications of small vessel disease: White matter changes, lacunes, and microbleeds are all visible expressions of small vessel disease (SVD). The cognitive impact of SVD has gained interest in the last decades. In this section, we review: (1) the cognitive impact of the different types of SVD; (2) the influence of other clinical variables on cognition of subjects with SVD; and (3) the neuropsychological approach. Cognitive implications of white matter changes: Age-related white matter changes (WMCs) are frequent findings in magnetic resonance imaging (MRI) of elderly individuals in population-based studies [1-3]. In the Rotterdam Scan Study only 5% of the 1077 subjects aged between 60 and 90 years, randomly sampled from the general population, were free of any WMCs [1]. Among the 3301 subjects aged over 65 years from the community included in the Cardiovascular Health Study, only 4.4% were free of any abnormal signal in the white matter [2]. Even in younger ages (under 55 years), mild WMCs are frequently described in asymptomatic subjects [4], and prevalence is increased in symptomatic subjects in population studies. A clear increase with age has been reported over the different studies [1-4].

The psychiatry of stroke, second edition

Article

Dec 2012

D. Peter Birkett

Treating stroke requires attention not only to patients physical needs, but to their psychiatric needs as well. Unfortunately, there has been a considerable lack of literature that tackles this important facet of recovery. The Psychiatry of Stroke fills this void through a comprehensive examination that explores the mental and physical issues faced by stroke patients and offers up-to-date treatment options.

The Role of Cerebrovascular Disease in Cognitive Decline

Chapter

Mar 2014

Ana Verdelho

Vascular risk factors and cerebrovascular disease are recognized factors implicated in the evolution toward dementia, not only of vascular origin but also degenerative dementia as Alzheimer's disease. Even among nondemented subjects, hypertension, diabetes, and stroke are associated with worse performance in attention, executive functions, and speed and motor control. Infl uence of vascular risk factors in cognition starts early in life. Treatment and control of vascular risk factors since early ages has a key role in order to prevent cognitive impairment associated with aging. Cerebral white matter changes have gained attention in the last decades and can represent a potential outcome in experimental studies aiming to reduce cerebrovascular burden.

Microangiopathies (Lacunes)

Chapter

Dec 2011

Lacunes

Chapter

Dec 2004

Risk factors for dementia

Article

Jan 2001

Catriona D. McCullagh

There is little doubt that dementia is a very common cause of disability and dependency in our society. Since dementia of whatever type is usually more common with increasing age, then as population demographics change, so will the prevalence of dementia. Dementia is a generic term and the objective for clinicians, once dementia is suspected, is to attempt to define the cause. Alzheimer's disease is the most common cause of dementia, and in most centres vascular dementia would feature as the next most common aetiology. In some centres, Lewy body dementia is the second most common cause. Mixed Alzheimer's disease and vascular dementia would also feature high on the list at most centres.

Epidemiology of non-AD dementias

Article

May 2004
CLIN NEUROSCI RES

Marjolijn Bornebroek

Dementia is a common neurodegenerative disorder that affects about 10% of the population over 65 years of age. A distinction can be made between primary degenerative dementias and dementia secondary to other diseases. This review focuses on the primary non-Alzheimer's disease (AD) dementias: vascular dementia (VaD), dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD). VaD is after AD most frequent subtype of dementia with a prevalence of about 1%, ranging from 0 to 10% mainly depending on the age group investigated and the criteria used. Its incidence rate is between 1.5 and 4.1 per 1000 person-years, with no clear difference between men and women and with possibly a higher incidence in East Asia compared to Canada and Europe. Most of the VaD cases are sporadic although there are some rare familial forms of VaD as cerebral autosomal dominant arteriopathy with subcortical infarctions and leukoencephalopathy and familial cerebral amyloid angiopathy. Important risk factors for sporadic VaD are cerebrovascular pathology (brain infarction, white matter lesions and brain atrophy), midlife hypertension, and diabetes leading to increasing risk ratios. A protective effect is often found for education and moderate use of alcohol. The association between VaD and amyloid β, cholesterol, and statin use remains unclear yet. DLB and FTD are less frequent forms of dementia with prevalence rates of, respectively, 0.1–0.6 and 0.002–0.015%. FTD affects people in their middle age, accounting for up to 10–20% of the presenile dementia cases. About 14% of the FTD cases are caused by an autosomal dominant tau-mutation. However, since the prevalence of sporadic FTD is relatively low, population-based epidemiological studies are hard to perform and no non-genetic risk factors are known yet. DLB is a relative common form of dementia in old age accounting for 15–20% of cases in hospital autopsy case-series. The only known possible risk factor for DLB is the presence of an apolipoprotein E ε4 allele.

Electromyography: prognosis and evaluation of the efficiency of therapy for Bell's palsy

Article

Full-text available

Sep 2011

The paper presents the results of clinical and electromyographic studies in 182 patients with idiopathic facial neuropathy (BellXs palsy). The most commonly studied parameters of electroneuromyography (ENMG) were compared to determine a good or poor prognosis for recovery. The most sensitive parameters were shown to be nerve excitability threshold in the acutest period (up to 5 days), M-response amplitude fall ratio on the affected and intact sides and reversibility of impaired irritability in the acute period (on days 10 to 14), and muscle denervation changes starting on day 21. The most sensitive ENMG parameters for the evaluation of the efficiency of performed therapy were changes in M-response amplitude and latency. Thus, ENMG can estimate disease prognosis and monitor treatment efficiency.

Hypertension in the very elderly

Article

Aug 2007

The world population is aging and disorders that are more prevalent in the elderly are of increasing importance. Hypertension falls into this category and has been linked to many adverse outcomes from stroke to mortality and dementia. Antihypertensive treatment has been shown to be successful in younger age groups but in those aged 80 years and over its benefits are not yet proven, and the risks and benefits of hypertension and antihypertensive treatment are unclear. Given this, it is useful to examine hypertension in the very elderly, the epidemiology, the likely impact of hypertension in this population, both physical and mental, and the as yet unclear issue of treatment. An ongoing, randomized, controlled trial in this age group will aid resolution of these issues and our understanding of this very elderly group.

Survival and early recourse to care for dementia: A population based study

Article

Aug 2014
ALZHEIMERS DEMENT

Background: A large proportion of dementia cases are still undiagnosed. Although early dementia care has been hypothesized to benefit both patients and families, evidence-based benefits are lacking. Thus, investigating the benefits for newly demented persons according to their recourse to care in the "real life" appears critical. Methods: We examined the relation between initial care recourse care and demented individuals' survival in a large cohort of incident dementia cases screened in a prospective population-based cohort, the Three-City Study. We assessed recourse to care for cognitive complaint at the early beginning of dementia when incident cases were screened. We classified patients in three categories: no care recourse, general practitioner consultation or specialist consultation. We used proportional hazard regression models to test the association between recourse to care and mortality, adjusting on socio-demographical and clinical characteristics. Results: Two hundred and fifty-three incident dementia participants were screened at the 2 year or 4 year follow-up. One third of the incident demented individuals had not consulted a physician for cognitive problems. Eighty-six (34.0%) individuals had reported a cognitive problem only to their general practitioner (GP) and 80 (31.6%) had consulted a specialist. Mean duration of follow-up after incident dementia was 5.1 years, during which 146 participants died. After adjustment on potential confounders, participants who had consulted a specialist early in the disease course presented a poorer survival than those who did not consult any physician (hazard ratio = 1.64, 95% confidence interval 1.03-2.62). There was a trend but no significant differential survival profile between participants who complained to their GP and those without any care recourse. Conclusion: Neither recourse to a specialist nor recourse to GP improve survival of new dementia cases. Those who had consulted a specialist early in the disease course even reported a worse life expectancy than those who did not.

Design and analysis of randomized clinical trials requiring prolonged observation of each patient. I. Introduction and design

Article

Full-text available

Jan 1977

The Medical Research Council has for some years encouraged collaborative clinical trials in leukaemia and other cancers, reporting the results in the medical literature. One unreported result which deserves such publication is the development of the expertise to design and analyse such trials. This report was prepared by a group of British and American statisticians, but it is intended for people without any statistical expertise. Part I, which appears in this issue, discusses the design of such trials; Part II, which will appear separately in the January 1977 issue of the Journal, gives full instructions for the statistical analysis of such trials by means of life tables and the logrank test, including a worked example, and discusses the interpretation of trial results, including brief reports of 2 particular trials. Both parts of this report are relevant to all clinical trials which study time to death, and wound be equally relevant to clinical trials which study time to other particular classes of untoward event: first stroke, perhaps, or first relapse, metastasis, disease recurrence, thrombosis, transplant rejection, or death from a particular cause. Part I, in this issue, collects together ideas that have mostly already appeared in the medical literature, but Part II, next month, is the first simple account yet published for non-statistical physicians of how to analyse efficiently data from clinical trials of survival duration. Such trials include the majority of all clinical trials of cancer therapy; in cancer trials,however, it may be preferable to use these statistical methods to study time to local recurrence of tumour, or to study time to detectable metastatic spread, in addition to studying total survival. Solid tumours can be staged at diagnosis; if this, or any other available information in some other disease is an important determinant of outcome, it can be used to make the overall logrank test for the whole heterogeneous trial population more sensitive, and more intuitively satisfactory, for it will then only be necessary to compare like with like, and not, by chance, Stage I with Stage III.

Design & analysis of randomized clinical trials requiring prolonged observation of each patient. II. Analysis and examples

Article

Full-text available

Feb 1977

Part I of this report appeared in the previous issue (Br. J. Cancer (1976) 34,585), and discussed the design of randomized clinical trials. Part II now describes efficient methods of analysis of randomized clinical trials in which we wish to compare the duration of survival (or the time until some other untoward event first occurs) among different groups of patients. It is intended to enable physicians without statistical training either to analyse such data themselves using life tables, the logrank test and retrospective stratification, or, when such analyses are presented, to appreciate them more critically, but the discussion may also be of interest to statisticians who have not yet specialized in clinical trial analyses.

Decreases in Regional Cerebral Blood Flow with Normal Aging

Article

Full-text available

Aug 1991

Positron emission tomographic (PET) images of regional cerebral blood flow (rCBF) from 30 normal, resting volunteers aged 30 to 85 years were analysed to identify areas where rCBF fell with age. Images were anatomically normalised, and a pixel-by-pixel linear regression was performed to remove differences in global CBF between subjects. Pixels at which rCBF then showed a significant (p less than 0.01) negative correlation with age were identified. They were displayed as a statistical parametric map (SPM) of correlations. We demonstrate an age-related decrease in adjusted rCBF in the cingulate, parahippocampal, superior temporal, medial frontal, and posterior parietal cortices bilaterally, and in the left insular and left posterior prefrontal cortices (omnibus significance, chi 2 = 2,291, p less than 0.0001, df = 1). Decreases in rCBF suggest a regionally specific loss of cerebral function with age. The affected areas were all limbic, or association, cortices. Therefore, these decreases may constitute the cerebral substrate of the cognitive changes that occur during normal aging.

Frontal Systems Impairment Following Multiple Lacunar Infarcts

Article

Full-text available

Mar 1990
ARCH NEUROL-CHICAGO

To characterize cognitive impairments following multiple subcortical lacunar infarcts (lacunes), we prospectively compared the neuropsychological performance of 11 subjects with multiple lacunes with 11 medical control subjects matched for age and education who had no clinical or computed tomographic evidence of central nervous system disease. Subjects with multiple subcortical lacunes displayed neuropsychological signs of frontal system dysfunction, even though only 27% met the criteria for clinical diagnosis of dementia. They exhibited significant deficits in shifting mental set, response inhibition, and executive function. In addition, they were more often rated apathetic on a behavior-rating scale. We propose a continuum of cognitive impairments in lacunar states, ranging from frontal systems impairment to dementia.

Erkinjuntti T, Haltia M, Palo J, Sulkava R, Paetau AAccuracy of the clinical diagnosis of vascular dementia: a prospective clinical and post-mortem neuropathological study. J Neurol Neurosurg Psychiatry 51:1037-1044

Article

Full-text available

Sep 1988

Brains from a prospective study of demented patients were investigated post mortem. Of the 27 patients with clinical diagnosis of vascular dementia, 23 showed multiple cerebral infarcts but senile plaques and neurofibrillary tangles were absent or in insignificant numbers. This gives an accuracy of 85%, a figure higher than previously documented.

A white matter disorder in dementia of the Alzheimer type: A pathoanatomical study

Article

Full-text available

Mar 1986

In cases of Alzheimer's presenile and senile dementia, Alzheimer's disease (AD) and senile dementia of the Alzheimer type (SDAT), respectively, we have observed, in addition to the gray matter degeneration, a lesion that has the character of an incomplete infarction confined to the white matter. It is encountered in 60% of both groups, with mild changes in two thirds and moderate or severe changes in one third. It involves the deep white matter symmetrically, tapering off toward the cortex. It is characterized by partial loss of myelin, axons, and oligodendroglial cells; mild reactive astrocytic gliosis; and sparsely distributed macrophages as well as stenosis resulting from hyaline fibrosis of arterioles and smaller vessels. No complete or cavitating infarctions and no hypertensive vascular changes were observed. The white matter changes are thought to be due to hypoperfusion of the concerned white matter territories since, in addition to the white matter hyaline vascular stenosis, these cases show signs of cardiovascular disease, usually with hypotension. The white matter disorder also occurs independent of the gray matter process of AD and SDAT and may be seen as the sole brain lesion in non-AD subjects. Its occurrence is thus neither regularly related to the severity nor to the regional appearance and accentuation of the cortical Alzheimer process and is thus not likely to be just the result of a wallerian degeneration. Histologically it is similar in several respects to Binswanger's disease, although with some distinct differences. It is thus related to the cerebrovascular group of disorders in addition to AD and SDAT. In view of its frequency and severity, this white matter lesion is important to define, to diagnose, and ultimately to prevent or cure.

Etiology, prevention and treatment of vascular and multi-infarct dementia

Article

Jan 1988

Cerebral blood flow and metabolism in multi-infarct dementia: relationship to cognitive deficits

Article

Jan 1986

J.S. Meyer

Vascular Dementia and Dementia of the Alzheimer Type

Article

Jul 1988
ARCH NEUROL-CHICAGO

Judith Aharon-Peretz

• Multi-infarct dementia (MID) and dementia of the Alzheimer type (DAT) were compared with regard to ventricular size and leuko-araiosis (LA) on computed tomographic scans. Ninety-seven percent of patients with MID and 55.5% of patients with DAT had evidence of LA. The severity of LA was scored with a 0 through 4 rating system, and LA was found to be significantly more severe in patients with MID than in patients with DAT. Patients with MID, but not those with DAT, exhibited correlations between enlargement of the third and lateral ventricles and severity of cognitive impairment.

A white matter disorder in dementia of the Alzheimer type

Article

Jan 1987
ALZ DIS ASSOC DIS

Loeb C, Gandolfo C, Mancardi GL, Primavera A, Tassinari T: The lacunar syndromes: Review with personal contribution, in Lechner H, Meyer JS, Ott EO (eds): Cerebrovascular Disease: Research and Clinical Management. Amsterdam, Elsevier Science Publishing Co Inc, 1986, pp 107-156

Chapter

Jan 1986

Alberto Primavera

Vascular Dementia

Article

Nov 1990
DEMENT GERIATR COGN

Carlo Loeb

The current assessment of dementia due to vascular causes in terms of terminology, classification, clinical features and diagnostic criteria, neuropathological lesions, risk factors, and possible treatment is reported. The term vascular dementia (VD) covers all syndromes with dementia of vascular origin. The clinical workout may reach a diagnostic sensitivity ranging from 70 to 85%. Verified ischemic lesions associated with dementia include multiple large and small infarctions, multiple lacunes, and, less frequently, watershed infarctions and other vascular diseases. However, the pathological evidence of infarction does not necessarily mean that cerebral vascular lesions are responsible for a state of dementia. The mixed forms (degenerative and vascular dementia) are difficult to assess both from the diagnostic and neuropathological point of view. The etiology of VD is multifactorial.

Senile dementia of the Alzheimer type

Article

Nov 1983
ANN NEUROL

The prevalence of severe dementia in the United States is about 1.3 million cases, of which at least 50 to 60% are of the Alzheimer type. Severe dementia of the Alzheimer type is found rarely in a clearly dominant pattern, although often one or more relatives are affected. Down's syndrome in adults is often associated with Alzheimer changes. The diagnosis is a clinicopathological one; there is a considerable error rate in the clinical diagnosis early in the course of the disease, especially in regard to dementia in depression. The differential diagnosis involves a great many disorders, including multi-infarct dementia, tumors, subdural hematomas, and others. Physiological aspects of Alzheimer's disease include a diffusely slow electroencephalogram, reduced cerebral blood flow, and particular patterns noted on positron emission tomographic scanning. The latter technique has also demonstrated that oxygen extraction is normal in Alzheimer's disease, thus excluding ischemia from possible pathogenetic factors. Morphological changes, that is, the presence of plaques and tangles, are widely distributed in neocortex, paleocortex, and many deep gray areas down through the pontine tegmentum, but largely exclude the basal ganglia, thalamus, and substantia nigra. Numerous plaques without neocortical tangles are found in many demented persons older than 75 years. A severe loss of large neocortical neurons is characteristic of the disease. The chemical nature of the paired helical filaments that make up the neurofibrillary tangle has not yet been ascertained. Neurons are markedly deficient in the basal forebrain nuclei, and this deficiency may account for the severe diminution of choline acetyltransferase and acetylcholine in the neocortex and palecortex. Muscarinic cholinergic receptors are present in normal amounts. Norepinephrine is reduced in some cases, and somatostatin in most. Substance P is low in severe cases. The etiology of the disorder is unknown and the role of aluminum is disputed. Management of patients with Alzheimer's disease is difficult, and neuroleptics are to be used with great caution because of their side effects. Substrate therapy has not been effective; physostigmine improves memory but is not suitable for general use. Trophic factors, gangliosides, and aluminum chelation are being investigated for use in pharmacological intervention.

Andrews RJTranshemispheric diaschisis. Stroke 22:943-949

Article

Aug 1991

R.J. Andrews

We review here the literature in both animal models and humans concerning electrical activity, blood flow, and metabolism in the hemisphere contralateral to unilateral cerebral ischemia. We analyze the data by periods based on the time from initial injury to emphasize the time course of transhemispheric diaschisis. Contralateral electrical activity, such as evoked potential amplitude, is increased in the late stages after unilateral infarction, with the data from the more acute periods being inconclusive. Contralateral blood flow changes probably depend on the magnitude of the ischemic injury, with a larger insult resulting in a decrease not seen with smaller insults. Some studies have shown a decrease in contralateral blood flow over the first week followed by a gradual return toward baseline. Most measures of contralateral metabolism show a time course similar to blood flow, that is, a decrease followed by gradual recovery. The effects of corpus callosum section on transhemispheric diaschisis are not yet established. We provide examples to show that under certain conditions, diaschisis may represent a loss of remote inhibition rather than a loss of remote facilitation, as von Monakow originally suggested. By following the contralateral changes over time, particularly during the first minutes and hours of ischemia, insight will be gained into the brain's responses remote from the focus of ischemic injury. These responses should bear a relation to the brain's defense mechanisms ipsilaterally to the region of ischemia.

Cerebral hypoperfusion correlates with mild and parenchymal loss with severe multi-infarct dementia

Article

Apr 1991
J NEUROL SCI

Relative contributions of two potential pathogenetic factors for cognitive impairments among patients with multi-infarct dementia (MID) are reported. Cognitive test scores were correlated with measures of cerebral hypoperfusion and loss of brain parenchyma. Local cerebral blood flow values were determined utilizing stable xenon contrasted computed tomography and volumes for brain parenchyma were estimated from ratios of volumes of infarcted brain plus cerebrospinal fluid/total intracranial volume measured on the same CT slices among two groups of patients, one with mild and the other with severe MID. A total of 26 demented patients with multiple cerebral infarcts were divided into 2 index groups, one with mild and the other with severe MID (mild MID, CCSE greater than or equal to 15, n = 16; severe MID, CCSE less than 15, n = 10). Results were compared with similar measures among age-matched neurologically normal volunteers (n = 14). Ratios for volumes of lost brain parenchyma were significantly higher among severe MID patients than among age-matched normal volunteers, whereas estimates of brain loss among patients with mild MID did not differ from elderly normal volunteers. In patients with mild MID, LCBF values for cortical gray matter were decreased compared with age-matched normal volunteers. Results suggest that chronic cerebral hypoperfusion is an important determinant for mild dementia among patients in the early stages of MID, but volumes of lost cerebral parenchyma due to cerebral infarctions is an important determinant for advanced stages of MID.

Clinical Correlates of White-Matter Changes on Magnetic Resonance Imaging Scans of the Brain

Article

Nov 1991
ARCH NEUROL-CHICAGO

We report our observations on the clinical and radiologic correlates of changes in cerebral white matter based on 94 subjects undergoing magnetic resonance imaging in a prospective study of dementia. Periventricular hyperintensity occurred twice as often in patients with Alzheimer's disease as in healthy control subjects. Within the control group, the presence of periventricular hyperintensity correlated significantly with one measure of cerebral atrophy and with the presence of changes in the adjoining deep white matter. The significance of white-matter changes distinct from the ventricles (leuko-araiosis) remains unsettled. Leuko-araiosis on the magnetic resonance imaging scan, unlike its correlate on the computed tomographic scan, was not shown to relate to cognitive decline or to the presence of focal abnormalities on neurologic examination. This is likely to reflect the heterogeneity of the changes detected with magnetic resonance imaging and their limited extent in our subjects.

Cerebral Blood Flow and Metabolism Studies in Multi-Infarct Dementia

Article

Feb 1991
ALZ DIS ASSOC DIS

In the last 40 years, blood flow and metabolism in the brain have been measured by many methods of varying resolution and reliability. Modern methods have helped to answer some basic pathophysiologic questions, in particular disproving ongoing global ischemia as a cause for dementia. But much of this physiologic work is confounded by swiftly changing clinical and pathologic understandings of ischemic and other forms of dementia: the field remains limited as much by unresolved clinical questions as by technologic feasibility.

The fallacy of the lacune hypothesis

Article

Oct 1990

We review the definition, pathogenesis, natural history, and prognosis and describe the first experimental model of lacunes. Defined pathologically or radiologically, lacunes are small cerebral infarcts which become cystic and are caused by occlusion of small arteries. The clinical definition of lacune is confused. The word "lacune" means a small stroke. While the immediate mortality rate from a small stroke is low, many patients are unable to return to work and the long-term prognosis is guarded. Photochemical damage to the carotid artery of rats produces microemboli to the brain, resulting in cavitary lesions resembling lacunes in humans. The "lacune hypothesis" is a fallacy because small cerebral infarcts are not caused solely by a combination of hypertension and small vessel disease, and the various "lacunar syndromes" are simply small strokes which should be investigated as such.

How acute brain failure becomes chronic: A view of the mechanisms of dementia related to stroke

Article

Dec 1990

T K Tatemichi

Effects of capsular or thalamic stroke on metabolism in the cortex and cerebellum: A Positron Tomography Study

Article

May 1990

We used positron emission tomography to study the cortical and cerebellar metabolic rates in 21 strictly selected patients with pure internal capsular infarct (n = 8), thalamocapsular hemorrhage (n = 6), or pure thalamic stroke (n = 7). Significant diffuse ipsilateral cortical hypometabolism relative to 62 controls free of cerebrovascular risk factors was frequently, although not consistently, found in the 13 patients with thalamocapsular or thalamic lesions and neuropsychological impairment but was absent from the eight patients with pure internal capsule infarct and free of neuropsychological deficit. These data suggest that damage to the thalamus or the thalamocortical projections is important in the development of ipsilateral cortical hypometabolism and that the latter may underlie the associated neuropsychological impairment. Significant contralateral cerebellar hypometabolism relative to 49 controls was found in three of six patients with pure internal capsule infarct, suggesting a pathogenetic role for the corticopontocerebellar system. However, the occurrence of hypometabolism in two of six patients with thalamic lesions indicates that this phenomenon may also result either from damage to the ascending cerebellothalamocortical system or indirectly from hypofunction of the cerebral cortex. No systematic association was observed between crossed cerebellar hypometabolism and ipsilateral ataxia.

Vascular dementia. A clinicopathological study

Article

May 1990
J NEUROL SCI

We have reviewed the clinical and pathological records of 40 aged patients who showed only vascular lesions on histological examination. They were followed up for 3.5 +/- 6.3 years before death, and in 28 cases the diagnosis of dementia was done during life. Demographic data, vascular and systemic illnesses, psychiatric neurological and neuropsychological disturbances, and pathological findings were compared between demented and non-demented patients. The number of strokes, several neurological and almost all neuropsychological disturbances, the volume of macroscopic cerebral infarct, especially in frontal, occipital and basal regions, the lacunar state and the white matter lesions, were significantly greater in demented patients. However most of them had less than 100 ml3 of brain infarct. The relative influence of each type of cerebral vascular lesion upon the dementia syndrome was determined by means of multivariate analysis. The volume of macroscopic cerebral infarct, the white matter lesion and the lacunar state showed quite similar contributions to mental deterioration.

Frontal white matter lesions and dementia in lacunar infarction

Article

Sep 1990

We studied the associations of mental deterioration and blood pressure with severity and location of lesions in the cerebral white matter of 35 patients (27 men and eight women) aged 52-84 (mean 70.9) years with multiple lacunar infarcts; 21 had no dementia and 14 were demented. Using magnetic resonance imaging to evaluate lesion severity, we determined that demented patients had more severe lesions than nondemented patients; this difference was especially prominent for lesions in the frontal lobe (p less than 0.001). Score on the dementia rating scale of Hasegawa et al was negatively correlated with severity of the lesions in the frontal lobe. Blood pressure was positively correlated with the severity of white matter lesions. We show that severity of lesions in the white matter, especially in the frontal lobe, is correlated with mental deterioration of patients with multiple lacunar infarcts. Because uncontrolled hypertension is related to the severity of such lesions, careful selection of antihypertensive treatment is important in preventing both the cerebral lesions and the associated mental deterioration.

Clinical Neuromythology VI Au clair de lacune: Holy, wholly, holey logic

Article

Jun 1989

William M Landau

Periventricular lesions on MRI: Facts and theories

Article

Aug 1989

Patchy subcortical lesions are frequently identified on magnetic resonance imaging (MRI) of the brain in the elderly. On computed tomography (CT) these lesions appear as periventricular zones of lucency and have been termed «leuko-araiosis» by Hachinski and colleagues. Despite limited knowledge of the pathological correlates of the lesions, there has been speculation about their nature, pathophysiology, and clinical significance

Dementia due to vascular disease - A multifactorial disorder

Article

Nov 1988

P Scheinberg

This review was undertaken to evaluate critically the literature pertaining to vascular dementia with the objective of determining a more useful and scientifically supported definition of vascular dementia, its relation to other causes of dementia, and the biologic mechanisms involved in its causation.

Vascular dementia and dementia of the Alzheimer type. Cognition, ventricular size, and leuko-araiosis

Article

Aug 1988
ARCH NEUROL-CHICAGO

Multi-infarct dementia (MID) and dementia of the Alzheimer type (DAT) were compared with regard to ventricular size and leuko-araiosis (LA) on computed tomographic scans. Ninety-seven percent of patients with MID and 55.5% of patients with DAT had evidence of LA. The severity of LA was scored with a 0 through 4 rating system, and LA was found to be significantly more severe in patients with MID than in patients with DAT. Patients with MID, but not those with DAT, exhibited correlations between enlargement of the third and lateral ventricles and severity of cognitive impairment.

Vascular Dementia Is Overdiagnosed

Article

Aug 1988
ARCH NEUROL-CHICAGO

John C.M. Brust

There are different kinds of vascular dementia.1 Ignoring indirect mechanisms (such as hydrocephalus following subarachnoid hemorrhage2), we might hypothesize a pathophysiologic spectrum. At one end would be circumscribed intellectual impairment from destruction of particular brain areas, for example, memory loss after inferior temporal lobe infarction.3 This type of dementia seldom produces diagnostic (or conceptual) difficulty. At the other end would be more insidiously progressive dementia from diffuse small-vessel pathology (Binswanger's disease).4-9 This type of dementia is understood by no one, and estimates of its prevalence range from infinitesimal to epidemic. Between these two extremes is cognitive loss from multiple lesions, none of which alone would be expected to cause intellectual impairment (multiinfarct dementia).10 This type of dementia is overdiagnosed. Two decades ago Tomlinson et al,11 comparing the brains of 50 old people with dementia with those of control subjects without dementia, diagnosed dementia of

Intellectual impairment and cerebral lesions in multiple cerebral infarcts. A clinical-computed tomography study

Article

Jun 1988

The relation between cerebral lesions studied by computed tomography and the dementia syndrome has been evaluated in 40 patients with multi-infarct dementia, in 44 nondemented subjects with multiple infarcts, and in 30 controls matched for age and sex. Our study of the volume of ischemic lesions showed a slightly greater loss of cerebral substance in patients with multi-infarct dementia than in nondemented subjects with multiple infarcts, particularly in subjects with unilateral focal lesions and in patients with bilateral multiple cortical and subcortical lesions. The dementia syndrome was significantly associated with multiple locations of lesions in the thalamic and cortical areas supplied by the middle cerebral arteries. Moreover, patients with the dementia syndrome showed a significantly higher degree of cerebral atrophy than nondemented subjects and controls as evaluated by measurements of ventricular size, area of ventricular space, and area of subarachnoid space.

The brain diseases causing senile dementia. A morphological study on 54 consecutive autopsy cases

Article

May 1986

Brains from 54 patients with organic dementia were examined systematically. As in previous investigations a predominance of Alzheimer type changes was observed. Seventeen patients showed Lewy bodies in the nucleus basalis, the substantia nigra and the locus coeruleus as well as other lesions of parkinsonian type. In 5 cases these changes were thought to be responsible for dementia. In 8 patients no convincing morphological substrate of dementia was found. These patients were older than average; therefore age per se might have been responsible for dementia. It is emphasized that subjective judgements are almost unavoidable in assessing the cause of organic dementia.

Epidemiology of clinically diagnosed Alzheimer's Disease

Article

May 1986

This report reviews the current status of descriptive and analytic epidemiology of clinically diagnosed Alzheimer's disease (AD). Since AD can be diagnosed with certainty only at autopsy, currently available epidemiological data are based on a presumed clinical diagnosis. Current data indicate that AD represents a major health problem, at least in the developed countries. The prevalence ratio for AD ranges between 1.9 and 5.8 cases per 100 population aged 65 and over. Moreover, its prevalence is likely to increase in the next twenty years as a consequence of current demographic trends. The prevalence ratio for AD increases steeply with age and is higher in females. Incidence rates show a similar pattern, suggesting that AD should not be subdivided in a presenile and a senile form based on age of onset alone. Annual incidence rates of 2.4 cases per 100,000 population between ages 40 and 60, and 127 cases per 100,000 population after age 60 have been reported. Several case-control studies show that the occurrence of either dementia or Down's syndrome in other family members, advanced age of the mother at subject's birth, and head injury are possible risk factors.

The Clinical Diagnosis of Alzheimer's Disease

Article

Feb 1987
ARCH NEUROL-CHICAGO

Clinical and pathologic diagnoses are compared in 65 patients who had dementia and who had been studied longitudinally during life. The sensitivity of diagnosis for dementia of the Alzheimer type (DAT) without any other diagnosis was 87%, and the specificity was 78%. The ischemic scale score did not discriminate well between patients with pure multi-infarct dementia and those with both DAT and multi-infarct dementia. However, 35 of 38 cases of pure DAT had a score of 4 or less on the ischemic scale.

[Cerebral blood flow and metabolism in multi-infarct dementia]

Article

Oct 1985

Cerebral blood flow and oxygen metabolism were studied in three aged normal volunteers and 10 patients with multi-infarct dementia (MID) by Positron Emission Tomography using O-15. The diagnosis of MID was done according to the Loeb's modified ischemic score and X-ray CT findings. The MID patients, whose X-ray CT showed localized low density areas in the subcortical white matter and basal ganglia and thalamus, were studied. No occlusion was observed at anterior cerebral artery and/or middle cerebral artery on cerebral angiography. All cases of MID were mild dementias. Regional CBF, rOEF and rCMRO2 were measured by the steady state technique described by Terry Jones et al. The values of rCBF in MID patients were significantly low compared with those of aged normal subjects in frontal, temporal, occipital, parietal cortices and thalamus. The values of CMRO2 in MID were significantly low in frontal, temporal, occipital cortices and thalamus compared with normal subjects'. The OEF was 0.46 in aged normal subjects, and 0.52 in MID patients. The MID patients in the early stage of dementia showed the increased oxygen extraction fraction, and this fact suggests that ischemia is a significant pathogenic mechanism in the production and progression of multi-infarct dementia. The decrease of CBF and CMRO2 in MID compared from normal subjects' were most remarkable in frontal cortex. The impairment of mental functions in MID should be caused by the decreased neuronal activities in frontal association cortex.

Why do frontal lobe symptoms predominate in vascular dementia with lacunes?

Article

Apr 1986

We studied 30 necropsy cases of vascular dementia with a lacunar state. Manifestations included dementia, lack of volition, emotional lability, small-stepped gait, dysarthria, urinary incontinence, grasp reflex, pyramidal signs, paraplegia in flexion, and akinetic mutism. Pathologically, there was diffuse incomplete softening of white matter in all cases. Both lacunes and diffuse softening were found predominantly in the frontal lobes. The prominent clinical features were therefore frontal lobe symptoms, with good correlation between the symptoms and the distribution of pathologic lesions.

A new method of measuring brain atrophy: The effect of aging in its application for diagnosing dementia

Article

Oct 1985

A new method of measuring cerebral atrophy using a ratio of brain parenchyma to ventricular and subarachnoid space is described. It uses digitized brain CT. This ratio was measured prospectively on 117 consecutive elderly patients referred for evaluation of cognitive dysfunction. Diagnosis was determined by preestablished criteria and confirmed by follow-up. Despite the improved accuracy and reproducibility of this method, its ability to differentiate persons with senile dementia of the Alzheimer's type (SDAT) from those suffering from pseudodementia was confounded by age, and was hence of limited utility. We conclude that even with sophisticated measures of cerebral atrophy, CT is unable to discriminate among common causes of cognitive dysfunction in the elderly.

The Association Between Quantitative Measures of Dementia and of Senile Change in the Cerebral Grey Matter of Elderly Subjects

Article

Aug 1968

1. The association between plaque counts in sections of cerebral cortex and measures of intellectual and personality functioning undertaken in elderly subjects during life has been studied. 2. There was no evidence that degenerative changes had contributed significantly to the causation of illness in patients with "functional" psychiatric disorders or delirious states. 3. There is a highly significant correlation between mean plaque counts and scores for dementia and performance in psychological tests. The findings suggest that psychological and pathological indices are closely related to one another, possibly through their common association with the underlying degenerative process in the brain. 4. Among severely demented subjects and those diagnosed clinically as "senile dements", correlations between psychological and pathological measures decline sharply. However, pathological differences between normal, mildly demented, and severely demented subjects appear to be of a quantitative nature. The possibility that there are qualitative differences in this group, inaccessible to present methods of examination, cannot be excluded.

CT-CBF correlations of cognitive deficits in Multi-Infarct Dementia

Article

Nov 1984

Fifteen right-handed patients with Multi-Infarct Dementia underwent cognitive testing by the Jacobs Mini-Mental Scale (MMQ), and xenon contrast CT scanning. Local cerebral blood flow (LCBF) and local partition coefficient (L lambda) values were measured by stable xenon contrast CT scanning and potential methodological errors were discussed. Reduced values were graded: 0 = normal, 1 = mild, 2 = moderate, 3 = severe. Graded values were pooled and plotted on composite brain maps to display locations of abnormal L lambda and LCBF values. Topographic brain maps, showing most frequent locations of reduced L lambda values, confirmed the common anatomical locations of multiple cerebral infarcts to be distributed in both thalami, temporal lobes, basal ganglia, left internal capsule and right cingulate cortex. Gray matter flow values were reduced in similar cortical and subcortical regions. There were no correlations between MMQ scores and reduced LCBF values for caudate and lenticular nuclei. Direct and statistically significant correlations were found between reduced MMQ scores and mean LCBF values for left or right frontal cortex, left or right temporal cortex and left or right thalamus. Subgrouping MMQ tests according to functions assessed, indicated that left mid-temporal ischemia correlated with dyscalculia and memory disturbances while ischemia of both frontal lobes correlated with disorientation to time and place.

Vascular dementia - still overdiagnosed

Article

Mar 1983

J C Brust

Survival and recurrence following stroke: The Framingham Study

Article

May 1982

Survival and recurrences after stroke were assessed prospectively in a general population sample of 5184 subjects followed biennially for 26 years. Initial strokes occurred in 198 men and 196 women. There were 84 second and 27 third strokes and 223 deaths reported. Thirty day case-fatality rates for initial strokes were: 15% (33/222) for brain infarction, 16% (10/63) for cerebral embolus, 46% (18/39) for subarachnoid hemorrhage, and 82% (14/17) for intracerebral hemorrhage. Cumulative, age-adjusted 5 year survival rates for brain infarction were reduced by pre-stroke cardiac disease (coronary heart disease and/or congestive heart failure) and hypertension prior to initial stroke from .85 to .35 in men and .70 and .56 in women. Hypertension alone reduced survival from .85 to .51 in men, but not in women. Recurrences were primarily of the same type as the initial stroke. Cumulative 5 year recurrence rate for brain infarction was .42 for men, almost double that for women. Rates were reduced by excluding hypertensives and those with combined cardiac comorbidity and hypertension. Thus, risk of death or recurrence after stroke is substantial and profoundly influenced by sex and by cardiac comorbidity and hypertension present prior to the initial event.

A Clinical Approach to Vascular (Multiinfarct) Dementia

Article

Feb 1982

71 patients with an ischaemic stroke were investigated clinically, by psychological tests (WAIS) and Computertomography. On the basis of the investigation the patients were separated into two groups. 40 patients showed early dementia; 31 were without mental impairment. The frequency of strokes, the history of neurological symptoms and the neurological symptoms at admission were distributed evenly. The dominant hemisphere was significantly more often diseased in the demented group; bilateral signs were also significantly more often seen in the demented group. From the investigated risk factors (Hypertension, Cardiac disease, Diabetes, Viscosity, Fibrinogen). Only hypertension was significantly more often present in demented than non demented patients. The CT confirmed the clinical findings, especially the importance of the bilateral distribution of infarcts as well as a higher distribution of infarction in the thalamus in the demented patient group.

Transhemispheric diaschisis: A review and comment

Jan 1991
943-949

Rj Andrews

Andrews RJ: Transhemispheric diaschisis: A review and comment. Stroke 1991;22:943-949

Lacunar dementia Senile Dementia of the Alzheimer's Type

Jan 1985
1-21

Gc Roman

Roman GC: Lacunar dementia, in Hutton JT, Kenny AD (eds): Senile Dementia of the Alzheimer's Type. New York, Alan R Liss Inc, 1985, pp 1-21

Results of a five year prospective study of 94 patients with vascular and multi-infarct dementia in

H Lechner
Bertha
E O Ott

Lechner H, Bertha G, Ott EO: Results of a five year prospective study of 94 patients with vascular and multi-infarct dementia, in Meyer JS, Lechner H, Marshall J, Toole JF (eds): Vascular and Multi-infarct Dementia. Mount Kisco, NY, Futura Publishing Co Inc, 1988, pp 101-111

Handbook of Clinical Neurology Revised Series 2, Neurobehavioral Disorders

Jan 1985
353-369

C Loeb

Loeb C: Vascular dementias, in Frederiks JAM (ed): Handbook of Clinical Neurology Revised Series 2, Neurobehavioral Disorders. Amsterdam, Elsevier Science Publishing Co Inc, 1985, vol 46, pp 353-369

The lacunar syndromes: Review with personal contribution in

C Loeb
G L Gandolfo C Mancardi
Primavera
T Tassinari

Vascular dementias, in Frederiks JAM (ed): Handbook of Clinical Neurology Revised Series 2, Neurobehavioral Disorders. Amsterdam

Jan 1985
353

Loeb C

Dementia associated with lacunar infarction

Abstract

No full-text available

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