Post-stroke Dementia Research Articles

Biomarkers of vascular cognitive impairment

There is currently no approved list of vascular cognitive impairment biomarkers. The main problem for the practitioner in identifying cognitive impairment in patients is the differential diagnosis of Alzheimer's disease, vascular cognitive impairment, and other diseases, which are much less common. Vascular cognitive impairment includes post-stroke dementia, cognitive dysfunction in cardio-and cerebrovascular diseases. Without etiology identification, it is impossible to prescribe adequate treatment. Another challenge is identifying cognitive impairment before dementia develops. This literature review is devoted to the search and critical analysis of candidates for biomarkers of vascular cognitive impairment and the establishment of markers of moderate cognitive dysfunction. The papers were searched for in the Web of Science and PubMed databases. A list of cerebrospinal fluid, plasma, serum and genetic biomarkers was made, allowing for differential diagnosis between vascular impairment and Alzheimer's disease. The markers of moderate cognitive dysfunction, which make it possible to identify cognitive impairment at the pre-dementia stage, were also identified.

Everyday Abilities Scale for India in Screening for Poststroke Dementia Among Young Stroke Survivors.

Cognitive dysfunction after stroke is an important concern. We explored the utility of everyday abilities scale for India (EASI) for screening for dementia among young stroke survivors. We interviewed 150 young stroke survivors and caregivers. Vascular dementia was diagnosed according to American Heart Association-American Stroke Association (ASA-AHA) criteria. EASI was administered to all caregivers. Receiver operating characteristic curve analysis was used to determine the area under the curve and optimum cut-points for EASI for the identification of dementia. Median EASI scores among subjects with dementia (n=35; 23.3%) was 2 (interquartile range: 0-4) and significantly different from those without (median: 0; interquartile range: 0-1; P<0.001). The area under the curve was 0.768 (95% confidence interval: 0.674-0.863), and at the optimum cut-point of 2 on EASI, a sensitivity of 60% and specificity of 91.3% was achieved for the identification of dementia. EASI appears to be a promising tool to screen for dementia among young stroke survivors.

A Rare Case of Delayed‐Onset Post‐Stroke Dementia Associated with Cerebral Small Vessel and Alzheimer's Disease Pathologies

Background For individuals surviving a stroke, the prevalence of delayed-onset post-stroke dementia (PSD) is 4-24% as compared to ~20% for early-onset PSD, which has a major contributing factor (30-50%) of pronounced Alzheimer's disease (AD) pathology. However, severe sporadic cerebral small vessel disease (cSVD) appears to play a dominant role (~60%) in the development and progression of delayed-onset PSD while the contribution from pronounced AD pathology diminishes to ~20%. The significance of severe sporadic cSVD is also underscored by the fact that it may trigger additional pathological processes, independent of recurrent strokes. The original view on the two major pathologies contribution to PSD was that they develop independently of one another, but researchers are now investigating the common etiology shared between the two, particularly through their underlining genetics. The latter, however, has been significantly complicated by their polygenic nature. Therefore, a combination of thorough postmortem histopathological examination and a genetic screen using the Next Generation Sequencing (NGS) platform could provide a powerful tool to address the above shortcomings. Results We report an 85-year-old, male cadaver who suffered a major stroke at age 59 which resulted in right-side paralysis and aphasia, followed by the onset of dementia 22 years later. Upon gross inspection of the brain, a large necrotic area was visible on the left hemisphere. Histological examination of the brain tissue stained with hematoxylin and eosin (H&E) revealed several important pathologies. These included the presence of neurofibrillary tangles and amyloid plaques in the hippocampus and frequent amyloid plaques in the cerebral cortex, indicating AD neuropathological changes. Upon further examination, thickened arterial walls, enlarge perivascular spaces, arteriolosclerosis, microbleeds, and white matter rarefactions were also noted and consistent with features of cSVD. Subsequent staining using the Bielschowsky method, on brain tissue procured from the same areas, confirmed the H&E staining results while showing some positive staining of vessel walls that might be consistent with amyloid angiopathy, further suggesting cSVD presence. In order to gain insights into the molecular mechanisms underlining the observed brain pathologies, the whole coding region (exome) sequencing of the DNA extracted from the cadaveric tissue was performed on the Ilumina NGS platform. This genetic screen identified ~ 200 rare, deleterious genetic variants with the minor allele frequency of ≤ 1%. Among those variants, the most intriguing was the presence of the mucin gene family members, MUC2, MUC4, MUC6, and MUC16; previously linked to AD (MUC6 & MUC16), cerebrovascular pathology (MUC16), and dementia (MUC2 & MUC4). Conclusion The current case highlights potentially additive, or synergistic, involvement of AD and cSVD pathologies into the development of delayed-onset PSD. As the mucin gene family is highly expressed in the gut, the observed genetic polymorphisms may underscore the importance of the gut-vagus nerve-brain axis in delayed-onset PSD.

Investigation of dementia awareness among stroke patients in China: A cross-sectional study

Abstract Objective To provide guidelines for the prevention of post-stroke dementia, we investigated whether stroke patients were aware of post-stroke dementia and their level of dementia-related knowledge. Methods Five dementia-related questions were designed. A field survey was conducted in a question-and-answer method using the designed questions. The surveys assessed 3000 stroke patients (2 weeks–6 months after stroke attacks) from 14 hospitals/clinical centers in 7 provinces and cities across China. Results Among 3000 stroke patients, 80.5% had heard of dementia, 39.1% knew that stroke can lead to dementia, 55.7% believed dementia can be prevented, 50.8% thought dementia can be cured, and only 8.8% had ever seen a doctor because of memory deterioration. Then, patients were classified into three groups, including a no cognitive impairment (NCI) group, a mild cognitive impairment (MCI) group, and a mild dementia (MD) group. Among the MCI and MD groups, only 8.7% (75/861) and 9.9% (64/649) of patients, respectively, had ever seen a doctor because of memory deterioration. According to our results, patients with a higher level of cognitive impairment had a lower awareness of dementia (P Conclusion The awareness of dementia in stroke patients in China is low, and the consultation rate is even lower. Moreover, patients with a higher level of cognitive impairment have a lower awareness of dementia. To improve public awareness and improve prevention, more emphasis should be put on education regarding post-stroke dementia. Routine cognitive function screening should be conducted on stroke patients as an effective way to assess dementia.

Post-stroke Neurogenesis: Friend or Foe?

The substantial clinical burden and disability after stroke injury urges the need to explore therapeutic solutions. Recent compelling evidence supports that neurogenesis persists in the adult mammalian brain and is amenable to regulation in both physiological and pathological situations. Its ability to generate new neurons implies a potential to contribute to recovery after brain injury. However, post-stroke neurogenic response may have different functional consequences. On the one hand, the capacity of newborn neurons to replenish the damaged tissue may be limited. In addition, aberrant forms of neurogenesis have been identified in several insult settings. All these data suggest that adult neurogenesis is at a crossroads between the physiological and the pathological regulation of the neurological function in the injured central nervous system (CNS). Given the complexity of the CNS together with its interaction with the periphery, we ultimately lack in-depth understanding of the key cell types, cell–cell interactions, and molecular pathways involved in the neurogenic response after brain damage and their positive or otherwise deleterious impact. Here we will review the evidence on the stroke-induced neurogenic response and on its potential repercussions on functional outcome. First, we will briefly describe subventricular zone (SVZ) neurogenesis after stroke beside the main evidence supporting its positive role on functional restoration after stroke. Then, we will focus on hippocampal subgranular zone (SGZ) neurogenesis due to the relevance of hippocampus in cognitive functions; we will outline compelling evidence that supports that, after stroke, SGZ neurogenesis may adopt a maladaptive plasticity response further contributing to the development of post-stroke cognitive impairment and dementia. Finally, we will discuss the therapeutic potential of specific steps in the neurogenic cascade that might ameliorate brain malfunctioning and the development of post-stroke cognitive impairment in the chronic phase.

Blood pressure, blood pressure variability and the risk of poststroke dementia.

High blood pressure and blood pressure variability are potential, modifiable risk factors of poststroke dementia. We aimed to investigate the association between achieved blood pressure, blood pressure variability and poststroke dementia. We studied 17 064 patients with noncardioembolic ischemic stroke included in the Prevention Regimen for Effectively avoiding Second Strokes (PRoFESS) trial. We analysed the data as a single observational cohort. We studied mean achieved SBP and DBP and blood pressure variability defined as coefficient of variation (SD/mean∗100). The association between blood pressure and dementia was investigated with logistic regression analysis, correcting for sociodemographic factors and cardiovascular risk factors. During 39 818 person-years of follow-up, 817 patients were diagnosed with dementia (2.1 per 100 person-years). We found a significant nonlinear association between mean SBP and the risk of dementia, implying a U-shaped association between mean SBP and dementia. Mean SBP of 120-129 mmHg was associated with a significantly higher risk of dementia than 130-139 mmHg [odds ratio (OR) 1.28; 95% confidence interval (95% CI) 1.03-1.58]. There was no indication of a U-shaped association between mean DBP and dementia, and no significant association between mean DBP categories and dementia. Higher blood pressure variability was associated with an increased risk of dementia (OR 1.06 per point increase, 95% CI 1.02-1.04), independent of mean SBP. Among patients with a recent noncardioembolic ischemic stroke, there appears to be a U-shaped association between achieved SBP and dementia. High blood pressure variability is associated with an increased risk of poststroke dementia.

Screening for Cognitive Impairment After Stroke: Validation of the Chinese Version of the Quick Mild Cognitive Impairment Screen.

Background: Screening for post-stroke cognitive impairment (PSCI) is necessary because stroke increases the incidence of and accelerates premorbid cognitive decline. The Quick Mild Cognitive Impairment (Qmci) screen is a short, reliable and accurate cognitive screening instrument but is not yet validated in PSCI. We compared the diagnostic accuracy of a Chinese version of the Qmci screen (Qmci-CN) compared with the widely-used Chinese versions of the Montreal Cognitive Assessment (MoCA-CN) and Mini-Mental State Examination (MMSE-CN).Methods: We recruited 34 patients who had recovered from a stroke in rehabilitation unit clinics in 2 university hospitals in China: 11 with post-stroke dementia (PSD), 15 with post-stroke cognitive impairment no dementia (PSCIND), and 8 with normal cognition (NC). Classification was made based on clinician assessment supported by a neuropsychological battery, independent of the screening test scores. The Qmci-CN, MoCA-CN, and MMSE-CN screens were administered randomly by a trained rater, blind to the diagnosis.Results: The mean age of the sample was 63 ± 13 years and 61.8% were male. The Qmci-CN had statistically similar diagnostic accuracy in differentiating PSD from NC, an area under the curve (AUC) of 0.94 compared to 0.99 for the MoCA-CN (p = 0.237) and 0.99 for the MMSE-CN (p = 0.293). The Qmci-CN (AUC 0.91), MoCA-CN (AUC 0.94), and MMSE-CN (AUC 0.79) also had statistically similar accuracy in separating PSD from PSCIND. The MoCA-CN more accurately distinguished between PSCIND and normal cognition than the Qmci-CN (p = 0.015). Compared to the MoCA-CN, the administration times of the Qmci-CN (329s vs. 611s, respectively, p < 0.0001) and MMSE-CN (280 vs. 611s, respectively, p < 0.0001) were significantly shorter.Conclusion: The Qmci-CN is accurate in identifying PSD and separating PSD from PSCIND in patients post-stroke following rehabilitation and is comparable to the widely-used MoCA-CN, albeit with a significantly shorter administration time. The Qmci-CN had relatively poor accuracy in identifying PSCIND from NC and hence may lack accuracy for certain subgroups. However, given the small sample size, the study is under-powered to show superiority of one instrument over another. Further study is needed to confirm these findings in a larger sample size and in other settings (countries and languages).

Abstract P765: Therapeutic Approaches to Reduce Post-Stroke Cognitive Impairment

Introduction: Cognitive impairments and memory loss are common after stroke, with an emerging awareness of a high risk of conversion to post-stroke dementia. It is increasingly clear that in addition to neuronal injury following cerebral ischemia, impaired functional networks contribute to long-term functional deficits. Synaptic plasticity (LTP) is the leading cellular model of learning and memory. Thus, we utilize electrophysiological recordings of hippocampal LTP as an indicator of network health following ischemia in combination with neurobehavioral assessments of memory function. Hypothesis: Focal ischemic stroke increases soluble amyloid beta (Aβ) in the hippocampus, causing impaired plasticity and memory function. Methods: Extracellular field recordings of CA1 neurons were performed in acute hippocampal slices prepared 30 days after recovery from transient MCAO (45 min) in adult (6-8 week) mice. A behavioral fear conditioning paradigm (CFC) was used to evaluate memory. ELISA assay was used to quantify soluble Aβ42 from the hippocampus. Slices were treated with Aβ42 oligomers with and without our newly developed peptide inhibitor of TRPM2, termed tatM2NX. Results: Recordings from brain slices 30 days after MCAO showed near complete loss of LTP; 161±9%, n=6 in sham compared to 115±4%, n=7 30 days after MCAO in the hippocampus. MCAO decreased freezing behavior, indicating lack of memory (65±7% in sham mice (n=6) and 37±7% in MCAO mice, n=7). We observed a 48% increase in Aβ42 in the hippocampus 30 days after MCAo. We observed that addition of Aβ42 oligomers (500 nM) impaired LTP. This impaired LTP was prevented with co-application of the TRPM2 channel inhibitor tatM2NX. Consistent with a role of TRPM2 channels in post-stroke cognitive impairment, MCAO mice treated with tatM2NX (20 mg/kg iv injection 24 hr before testing) on day 29 post MCA demonstrated increasing freezing to 72±5% (n=9). Conclusion: Our data implicates increased levels of soluble Aβ42 in the hippocampus following stroke, resulting in activation of TRPM2 channels and impaired synaptic plasticity. Therefore, reducing soluble Aβ42 and/or inhibition of TRPM2 channels at chronic time points following ischemia may represent a novel strategy to improve functional recovery following stroke.

Current view on post-stroke dementia.

Dementia is one of the leading complications after stroke affecting about one third of survivors. Prevalence of post-stroke dementia (PSD) differs between studies due to variability in methodology, characteristics of included patients, type of stroke, diagnostic tools used to identify patients with dementia, or time when the assessment was performed. Patients diagnosed with PSD are at higher risk of mortality, disability, and institutionalization. Aetiology of PSD may include mixed overlapping processes such as vascular brain pathology or Alzheimer's disease. Several risk factors have been found to increase PSD incidence, involving demographics, vascular factors, stroke characteristics, abnormalities on neuroimaging, and stroke complications. However, the influence of some other factors still remains unclear. PSD may coexist with other neuropsychiatric disorders and its association with post-stroke depression seems to be the most significant. There is a strong need for further research on possible genetic, biological, and inflammatory biomarkers. Also, there are no unambiguously efficacious methods of management. Continuing to address these issues will help to find more effective interventions directly targeting prevention and treatment of PSD in the future.

Post-stroke dementia: frequency, predictors, and health impact

BackgroundCognitive impairment is an important aspect for stroke survivors. Little data are available about the frequency and risk factors of post-stroke dementia in Egypt.ObjectivesThe aim of this study is to evaluate the frequency and predictors of post-stroke dementia and its impact on outcome.MethodsA total of 380 patients with acute stroke were included. Patients were subjected to demographic data collection, neurological examination, and assessment of vascular risk factors. Furthermore, assessment of stroke severity by Barthel Index was done. After 6 months, patients were assessed for outcome and development of post-stroke dementia.ResultsPost-stroke dementia was detected in 20.8% of patient. It was recorded more in old ages, illiterates, unmarried, unemployed, and those with recurrent stroke and with cerebral infarction (significantly with cardio-embolic).ConclusionPost-stroke dementia is high in Egypt, especially in those with illiteracy, atrial fibrillation, brain atrophy, severe strokes, and those presented with hemiplegia, sphincter affection, abnormal gait, and psychotic features. Assessment for post-stroke dementia should be done during follow up of stroke patients.

Post-stroke dementia and permanent institutionalization

BackgroundDementia is among the most frequent causes of institutionalization. To serve the purpose of preventive strategies, there are no follow-up studies that have evaluated the actual impact of post-stroke dementia on institutionalization. We therefore compared the institutionalization rate and length of stay in an institutional care facility of patients with post-stroke dementia with stroke patients without dementia. MethodsWe included 410 consecutive patients aged 55 to 85 years with ischemic stroke who were admitted to Helsinki University Hospital (The SAM cohort). Hospitalization and nursing home admissions were reviewed from national registries. Dementia was diagnosed using the Diagnostic and Statistical Manual of Mental Disorders 3rd edition (DSM-III) criteria using extensive clinical assessments performed 3 months post-stroke. The cohort had a follow-up 21 years later. ResultsCompared to patients without dementia, post-stroke dementia was associated with shorter survival time (6.60 vs 10.10 years, p < 0.001), shorter time spent not institutionalized (5.40 vs 9.37 years, p < 0.001), but not with time spent permanently institutionalized (0.73 vs 1.10 years, p = 0.08). Post-stroke dementia was associated with higher rates and earlier permanent institutionalization compared to absence of post-stroke dementia (HR 1.53, 95% CI 1.07–2.18) in a Cox regression model adjusting for age, status of living alone at baseline, modified Rankin Scale at baseline, history of atrial fibrillation, and cardiac failure. ConclusionsPost-stroke dementia is associated with earlier permanent institutionalization. Due to significantly shorter survival, the time spent in nursing homes was not significantly longer in patients with post-stroke dementia compared with patients without post-stroke dementia.

Lack of association between acute stroke, post-stroke dementia, race, and β-amyloid status

IntroductionStroke and Alzheimer disease share risk factors and often co-occur, and both have been reported to have a higher prevalence in African Americans as compared to non-Hispanic whites. However, their interaction has not been established. The objective of this study was to determine if preclinical Alzheimer disease is a risk factor for stroke and post-stroke dementia and whether racial differences moderate this relationship. MethodsThis case-control study was analyzed in 2019 using retrospective data from 2007 to 2013. Participants were adults age 65 and older with and without acute ischemic stroke. Recruitment included word of mouth and referrals in Saint Louis, MO, with stroke participants recruited from acutely hospitalized patients and non-stroke participants from community living older adults who were research volunteers. Our assessment included radiologic reads of infarcts, microbleeds, and white matter hyperintensitites (WMH); a Pittsburgh Compound B PET measure of cortical β-amyloid binding; quantitative measures of hippocampal and WMH volume; longitudinal Mini Mental State Examination (MMSE) scores; and Clinical Dementia Rating (CDR) 1 year post-stroke. ResultsA total of 243 participants were enrolled, 81 of which had a recent ischemic stroke. Participants had a mean age of 75, 57% were women, and 52% were African American. Cortical amyloid did not differ significantly by race, stroke status, or CDR post-stroke. There were racial differences in MMSE scores at baseline (mean 26.8 for African Americans, 27.9 for non-Hispanic whites, p = 0.03), but not longitudinally. African Americans were more likely to have microbleeds (32.8% vs 22.6%, p = 0.04), and within the acute stroke group, African Americans were more likely to have small infarcts (75.6% vs 56.8%, p = 0.049). ConclusionPreclinical Alzheimer disease did not show evidence of being a risk factor for stroke nor predictive of post-stroke dementia. We did not observe racial differences in β-amyloid levels. However, even after controlling for several vascular risk factors, African Americans with clinical stroke presentations had greater levels of vascular pathology on MRI.

Altered hippocampal functional connectivity patterns in patients with cognitive impairments following ischaemic stroke: A resting-state fMRI study

BackgroundIschemic stroke with cognitive impairment is a considerable risk factor for developing dementia. Identifying imaging markers of cognitive impairment following ischemic stroke will help to develop prevention strategies against post-stroke dementia. MethodsWe investigated the hippocampal functional connectivity (FC) pattern following ischemic stroke, using resting-state fMRI (rs-fMRI). Thirty-three cognitively impaired patients after ischemic stroke and sixteen age-matched controls with no known history of neurological disorder were recruited for the study. No patient had a direct ischaemic insult to hippocampus on the examination of brain imaging. Seven subfields of hippocampus were used as seeds region for FC analyses. ResultsAcross all hippocampal subfields, FC with the inferior parietal lobule was reduced in stroke patients as compared with healthy controls. This decreased FC included both supramarginal gyrus and angular gyrus. The FC of hippocampal subfields with cerebellum was increased. Importantly, the degree of the altered FC between hippocampal subfields and inferior parietal lobule was associated with their impaired memory function. ConclusionOur results demonstrated that decreased hippocampal-inferior parietal lobule connectivity was associated with cognitive impairment in patients with ischemic stroke. These findings provide novel insights into the role of hippocampus in cognitive impairment following ischemic stroke.

Predictors of dementia after first ischemic stroke.

ABSTRACT.Various mechanisms contribute to dementia after first ischemic stroke as lesions on strategic areas of cognition and stroke premorbidity.Objectives: Assessing clinical and neuroimaging predictors of dementia after first ischemic stroke and its relation to stroke location, subtypes and severity.Methods: Eighty first ischemic stroke patients were included. Forty patients with dementia after first stroke and forty patients without dementia according to DSM-IV diagnostic criteria of vascular dementia. All patients were subjected to general and neurological assessment, National Institute Health Stroke Scale (NIHSS) for stroke severity, Montreal Cognitive Assessment (MoCA) scale for cognition assessment, MRI brain and Trial of Org 10172 in acute stroke treatment (TOAST) classification for stroke subtypes.Results: Left hemispheric ischemic stroke, strategic infarctions, diabetes mellitus and stroke of anterior circulation were found to be independent risk factors for dementia after first ischemic stroke (OR=3.09, 95%CI 1.67-10.3, OR=2.33, 95%CI 1.87-8.77, OR=1.88, 95%CI 1.44-4.55, OR=1.86, 95%CI 1.45-6.54, respectively). Hypertension, dyslipidemia, smoking, ischemic heart disease, high NIHSS score and large vessel infarction were significantly higher among post stroke dementia patients. However, on binary logistic regression, they did not reach to be independent risk factors.Conclusion: Stroke location (left stroke, strategic infarction, anterior circulation stroke) and diabetes mellitus could be predictors of dementia after first ischemic stroke, but stroke severity, stroke subtypes, hypertension, dyslipidemia, smoking and ischemic heart could not.

Effect of acupuncture treatment on post-stroke cognitive impairment: A randomized controlled trial.

Introduction:Post-stroke cognitive impairment (PSCI), which has a high morbidity, is closely associated with the recurrence and rehabilitation of ischemic stroke. There are 2 different stages of PSCI, including post-stroke cognitive impairment with no dementia (PSCIND) and post-stroke dementia (PSD). The latter has a significantly higher mortality rate than the previous one. Therefore, preventing the onset of PSD is of vital importance. However, there is no unequivocally effective prevention or treatment for PSCI, except intensive secondary prevention of stroke. The primary aim of this protocol is to explore whether acupuncture can improve cognitive function of patients with PSCIND and reduce the chances of developing PSD. On this bias, we also want to explore its possible mechanisms.Methods and analysis:A prospective, multicenter, large sample, randomized controlled trial will be conducted. A total of 360 eligible patients will be recruited from 5 different hospitals and randomly allocated into the acupuncture group (AG), sham acupuncture group (NAG), and waiting-list group (WLG) in a 1:1:1 ratio. The intervention period of NAG and AG will last 3 months (30 minutes per day, 3 times per week). Primary and secondary outcomes will be measured at baseline, 12 weeks (at the end of the intervention), 24 weeks (after the 12-week follow-up period), and 36 weeks (after the 24-week follow-up period). Resting-state and task-state functional MRI will be conducted at baseline and 12 weeks.Ethics and dissemination:The ethic committee of First Teaching Hospital of University of Traditional Chinese Medicine approved the study. Study results will be first informed to each participant and later disseminated to researchers, and the general public through courses, presentations and the internet, regardless of the magnitude or direction of effect. The results will also be documented in a published peer-reviewed academic journal.Registration:We have registered at ClinicalTrials.gov(ChiCTR2000033801).

The role of brain-derived neurotrophic factor (BDNF) in the development of vascular cognitive impairment

Brain-derived neurotrophic factor (BDNF) is principally involved in the phenomena of neuroplasticity of the brain and long-term synaptic potency (LTP) in the hippocampus. This article covers the role played by BDNF as a diagnostic marker of vascular cognitive disorders. The relationship between etiology and the degree of cognitive impairment with the level of BDNF is ambiguous. Especially if we take into account the fact that vascular pathology can be a trigger for molecular mechanisms of neurodegeneration. The lowest BDNF level can be found among patients with dementia in Alzheimer’s disease, and there is evidence that patients with neurodegenerative disease without cognitive impairment have a decreased BDNF level. Patients with vascular cognitive impairment have a less expressed decrease of BDNF level, although it can depend on severity of stroke. In case of vascular cognitive impairment, it is possible to improve cognitive state thanks to increased BDNF level in hippocampus after physical activity. That opens new opportunities in rehabilitation. Genetic polymorphism of BDNF leads to the problems with cognitive rehabilitation and increases the risk of post-stroke dementia and dementia in Alzheimer’s disease. Supposedly, changes in the structure of BDNF-propeptide, which is involved in the processes of long-term synaptic depression (LTD) of the hippocampus, are the main cause in this case.

Impact of multimorbidity on risk and outcome of stroke: Lessons from chronic kidney disease.

With both an aging population and greater post-stroke survival, multimorbidity is a growing healthcare challenge, affecting over 40% of stroke patients, and rising rapidly and predictably with increasing age. Commonly defined as the co-occurrence of two or more chronic conditions, multimorbidity burden is a strong adverse prognostic factor, associated with greater short- and long-term stroke mortality, worse rehabilitation outcomes, and reduced use of secondary prevention. Chronic kidney disease can be considered as the archetypal comorbidity, being age-dependent and also affecting about 40% of stroke patients. Chronic kidney disease and stroke share very similar traditional cardiovascular risk factor profiles such as hypertension and diabetes, though novel chronic kidney disease-specific risk factors such as inflammation and oxidative stress have also been proposed. Using chronic kidney disease as an exemplar condition, we explore the mechanisms of risk in multimorbidity, implications for management, impact on stroke severity, and downstream consequences such as post-stroke cognitive impairment and dementia.

Frequency of Cognitive Impairment Among Malaysian Elderly Patients Following First Ischaemic Stroke-A Case Control Study.

Background: Stroke is highly prevalent globally and is an important cause of cognitive impairment and dementia.Aims: We determined the frequency of post-stroke cognitive impairment (PSCI) at 1, 3, and 6 months among patients with first clinical ischemic stroke compared to risk and age-matched controls.Methods: This study involved 32 cases and 32 controls, and was conducted over 6 months. Cases were inpatients aged >60 with first clinical ischemic stroke. Controls were age-matched subjects without prior stroke. Montreal Cognitive Assessment (MoCA) was performed in all patients at 1, 3, and 6 month post stroke. A MoCA score of <26 was used for mild PSCI and <22 for moderate PSCI (post stroke dementia).Results: Post-stroke dementia was detected in 12 patients (37.5%) at 1st month, in 13 (40.6%) at 3rd month and 15 (48.4%) at 6th months. Mild PSCI was present in 7 patients (21.6%) at 1 month, 16 patients (50%) at 3 months, and 15 patients (48%) at 6 months. The odds ratio (OR) for post-stroke dementia was 3.2 (95%CI 0.98–10.68; p = 0.05) at 1 month; 3.69(95% CI 1.13–12.11; p = 0.031) at 3 months, and 4.88 (95% CI 1.49–15.99; p = 0.009) at 6 months. Years of education was an independent predictor for dementia (OR 0.60; p = 0.046). The OR for post-stroke dementia at 6th month was 7.23 with education level adjusted (95%CI 1.46–35.86, p = 0.015).Conclusion: The frequency of PSCI was high as early as 1 month after stroke. Stroke alone conferred a 7.2 times risk for post-stroke dementia compared to controls.

Testing a convolutional neural network-based hippocampal segmentation method in a stroke population.

As stroke mortality rates decrease, there has been a surge of effort to study poststroke dementia (PSD) to improve long‐term quality of life for stroke survivors. Hippocampal volume may be an important neuroimaging biomarker in poststroke dementia, as it has been associated with many other forms of dementia. However, studying hippocampal volume using MRI requires hippocampal segmentation. Advances in automated segmentation methods have allowed for studying the hippocampus on a large scale, which is important for robust results in the heterogeneous stroke population. However, most of these automated methods use a single atlas‐based approach and may fail in the presence of severe structural abnormalities common in stroke. Hippodeep, a new convolutional neural network‐based hippocampal segmentation method, does not rely solely on a single atlas‐based approach and thus may be better suited for stroke populations. Here, we compared quality control and the accuracy of segmentations generated by Hippodeep and two well‐accepted hippocampal segmentation methods on stroke MRIs (FreeSurfer 6.0 whole hippocampus and FreeSurfer 6.0 sum of hippocampal subfields). Quality control was performed using a stringent protocol for visual inspection of the segmentations, and accuracy was measured as volumetric correlation with manual segmentations. Hippodeep performed significantly better than both FreeSurfer methods in terms of quality control. All three automated segmentation methods had good correlation with manual segmentations and no one method was significantly more correlated than the others. Overall, this study suggests that both Hippodeep and FreeSurfer may be useful for hippocampal segmentation in stroke rehabilitation research, but Hippodeep may be more robust to stroke lesion anatomy.

Characterization of Tauopathy in a Rat Model of Post-Stroke Dementia Combining Acute Infarct and Chronic Cerebral Hypoperfusion.

Post-stroke dementia (PSD) is a major neurodegenerative consequence of stroke. Tauopathy has been reported in diverse neurodegenerative diseases. We investigated the cognitive impairment and pathomechanism associated with tauopathy in a rat model of PSD by modeling acute ischemic stroke and underlying chronic cerebral hypoperfusion (CCH). We performed middle cerebral artery occlusion (MCAO) surgery in rats to mimic acute ischemic stroke, followed by bilateral common carotid artery occlusion (BCCAo) surgery to mimic CCH. We performed behavioral tests and focused on the characterization of tauopathy through histology. Parenchymal infiltration of cerebrospinal fluid (CSF) tracers after intracisternal injection was examined to evaluate glymphatic function. In an animal model of PSD, cognitive impairment was aggravated when BCCAo was combined with MCAO. Tauopathy, manifested by tau hyperphosphorylation, was prominent in the peri-infarct area when CCH was combined. Synergistic accentuation of tauopathy was evident in the white matter. Microtubules in the neuronal axon and myelin sheath showed partial colocalization with the hyperphosphorylated tau, whereas oligodendrocytes showed near-complete colocalization. Parenchymal infiltration of CSF tracers was attenuated in the PSD model. Our experimental results suggest a hypothesis that CCH may aggravate cognitive impairment and tau hyperphosphorylation in a rat model of PSD by interfering with tau clearance through the glymphatic system. Therapeutic strategies to improve the clearance of brain metabolic wastes, including tau, may be a promising approach to prevent PSD after stroke.