Post-stroke dementia - a comprehensive review

Post-stroke dementia (PSD) or post-stroke cognitive impairment (PSCI) may affect up to one third of stroke survivors. Various definitions of PSCI and PSD have been described. We propose PSD as a label for any dementia following stroke in temporal relation. Various tools are available to screen and assess cognition, with few PSD-specific instruments. Choice will depend on purpose of assessment, with differing instruments needed for brief screening (e.g., Montreal Cognitive Assessment) or diagnostic formulation (e.g., NINDS VCI battery). A comprehensive evaluation should include assessment of pre-stroke cognition (e.g., using Informant Questionnaire for Cognitive Decline in the Elderly), mood (e.g., using Hospital Anxiety and Depression Scale), and functional consequences of cognitive impairments (e.g., using modified Rankin Scale). A large number of biomarkers for PSD, including indicators for genetic polymorphisms, biomarkers in the cerebrospinal fluid and in the serum, inflammatory mediators, and peripheral microRNA profiles have been proposed. Currently, no specific biomarkers have been proven to robustly discriminate vulnerable patients (‘at risk brains’) from those with better prognosis or to discriminate Alzheimer’s disease dementia from PSD. Further, neuroimaging is an important diagnostic tool in PSD. The role of computerized tomography is limited to demonstrating type and location of the underlying primary lesion and indicating atrophy and severe white matter changes. Magnetic resonance imaging is the key neuroimaging modality and has high sensitivity and specificity for detecting pathological changes, including small vessel disease. Advanced multi-modal imaging includes diffusion tensor imaging for fiber tracking, by which changes in networks can be detected. Quantitative imaging of cerebral blood flow and metabolism by positron emission tomography can differentiate between vascular dementia and degenerative dementia and show the interaction between vascular and metabolic changes. Additionally, inflammatory changes after ischemia in the brain can be detected, which may play a role together with amyloid deposition in the development of PSD. Prevention of PSD can be achieved by prevention of stroke. As treatment strategies to inhibit the development and mitigate the course of PSD, lowering of blood pressure, statins, neuroprotective drugs, and anti-inflammatory agents have all been studied without convincing evidence of efficacy. Lifestyle interventions, physical activity, and cognitive training have been recently tested, but large controlled trials are still missing

Subcortical volumes differ in Parkinson's disease motor subtypes: New insights into the pathophysiology of disparate symptoms

Objectives: Patients with Parkinson’s disease (PD) can be classified, based on their motor symptoms, into the Postural Instability Gait Difficulty (PIGD) subtype or the Tremor Dominant (TD) subtype. Gray matter changes between the subtypes have been reported using whole brain Voxel-Based Morphometry, however, the evaluation of subcortical gray matter volumetric differences between these subtypes using automated volumetric analysis has only been studied in relatively small sample sizes and needs further study to confirm that the negative findings were not due to the sample size. Therefore, we aim to evaluate volumetric changes in subcortical regions and their association with PD motor subtypes. Methods: Automated volumetric MRI analysis quantified the subcortical gray matter volumes of patients with PD in the PIGD subtype (n=30), in the TD subtype (n=30), and in 28 healthy controls. Results: Significantly lower amygdala and globus pallidus gray matter volume was detected in the PIGD, as compared to the TD subtype, with a trend for an association between globus pallidus degeneration and higher (worse) PIGD scores. Furthermore, among all the patients with PD, higher hippocampal volumes were correlated with a higher (better) dual tasking gait speed (r=0.30, p<0.002) and with a higher global cognitive score (r=0.36, p<0.0001). Lower putamen volume was correlated (r=-0.28, p<0.004) with higher (worse) freezing of gait score, an episodic symptom which is common among the PIGD subtype. As expected, differences detected between healthy controls and patients in the PD subgroups included regions within the amygdala and the dorsal striatum but not the ventral striatum, a brain region that is generally considered to be more preserved in PD.Conclusions: The disparate patterns of subcortical degeneration can explain some of the differences in symptoms between the PD subtypes such as gait disturbances and cognitive functions. These findings may, in the future, help to inform a personalized therapeutic approach

Cognitive state following stroke: the predominant role of preexisting white matter lesions.

Stroke is a major cause of cognitive impairment and dementia in adults, however the role of the ischemic lesions themselves, on top of other risk factors known in the elderly, remains controversial. This study used structural equation modeling to determine the respective impact of the new ischemic lesions' volume, preexisting white matter lesions and white matter integrity on post stroke cognitive state.Consecutive first ever mild to moderate stroke or transient ischemic attack patients recruited into the ongoing prospective TABASCO study underwent magnetic resonance imaging scans within seven days of stroke onset and were cognitively assessed one year after the event using a computerized neuropsychological battery. The volumes of both ischemic lesions and preexisting white matter lesions and the integrity of the normal appearing white matter tissue were measured and their contribution to cognitive state was assessed using structural equation modeling path analysis taking into account demographic parameters. Two models were hypothesized, differing by the role of ischemic lesions' volume.Structural equation modeling analysis of 142 patients confirmed the predominant role of white matter lesion volume (standardized path coefficient β =  -0.231) and normal appearing white matter integrity (β =  -0.176) on the global cognitive score, while ischemic lesions' volume showed no such effect (β = 0.038). The model excluding the ischemic lesion presented better fit to the data (comparative fit index 0.9 versus 0.092).Mild to moderate stroke patients with preexisting white matter lesions are more vulnerable to cognitive impairment regardless of their new ischemic lesions. Thus, these patients can serve as a target group for studies on cognitive rehabilitation and neuro-protective therapies which may, in turn, slow their cognitive deterioration

Tracing the Neural Carryover Effects of Interpersonal Anger on Resting-State fMRI in Men and Their Relation to Traumatic Stress Symptoms in a Subsample of Soldiers

Uncontrolled anger may lead to aggression and is common in various clinical conditions, including post traumatic stress disorder. Emotion regulation strategies may vary with some more adaptive and efficient than others in reducing angry feelings. However, such feelings tend to linger after anger provocation, extending the challenge of coping with anger beyond provocation. Task-independent resting-state (rs) fMRI may be a particularly useful paradigm to reveal neural processes of spontaneous recovery from a preceding negative emotional experience. We aimed to trace the carryover effects of anger on endogenous neural dynamics by applying a data-driven examination of changes in functional connectivity (FC) during rs-fMRI between before and after an interpersonal anger induction (N = 44 men). Anger was induced based on unfair monetary offers in a previously validated decision-making task. We calculated a common measure of global FC (gFC) which captures the level of FC between each region and all other regions in the brain, and examined which brain regions manifested changes in this measure following anger. We next examined the changes in all functional connections of each individuated brain region with all other brain regions to reveal which connections underlie the differences found in the gFC analysis of the previous step. We subsequently examined the relation of the identified neural modulations in the aftermath of anger with state- and trait- like measures associated with anger, including brain structure, and in a subsample of designated infantry soldiers (N = 21), with levels of traumatic stress symptoms (TSS) measured 1 year later following combat-training. The analysis pipeline revealed an increase in right amygdala gFC in the aftermath of anger and specifically with the right inferior frontal gyrus (IFG).We found that the increase in FC between the right amygdala and right IFG following anger was positively associated with smaller right IFG volume, higher trait-anger level and among soldiers with more TSS. Moreover, higher levels of right amygdala gFC at baseline predicted less reported anger during the subsequent anger provocation. The results suggest that increased amygdala-IFG connectivity following anger is associated with maladaptive recovery, and relates to long-term development of stress symptomatology in a subsample of soldiers

CCR5 Is a Therapeutic Target for Recovery after Stroke and Traumatic Brain Injury.

We tested a newly described molecular memory system, CCR5 signaling, for its role in recovery after stroke and traumatic brain injury (TBI). CCR5 is uniquely expressed in cortical neurons after stroke. Post-stroke neuronal knockdown of CCR5 in pre-motor cortex leads to early recovery of motor control. Recovery is associated with preservation of dendritic spines, new patterns of cortical projections to contralateral pre-motor cortex, and upregulation of&nbsp;CREB and DLK signaling. Administration of a clinically utilized FDA-approved CCR5 antagonist, devised for HIV treatment, produces similar effects on motor recovery post stroke and cognitive decline post TBI. Finally, in a large clinical cohort of stroke patients, carriers for a naturally occurring loss-of-function mutation in CCR5 (CCR5-Δ32) exhibited greater recovery of neurological impairments and cognitive function. In summary, CCR5 is a translational target for neural repair in stroke and TBI and the first reported gene associated with enhanced recovery in human stroke

Summary of unadjusted and adjusted regressions for predicting global cognitive score one year after stroke.

<p>Summary of unadjusted and adjusted regressions for predicting global cognitive score one year after stroke.</p

Study population demographic and clinical measures, cognitive scores and brain MRI characteristics (data shown as mean ± SD or as number of cases and percentage n (%)).

<p>Study population demographic and clinical measures, cognitive scores and brain MRI characteristics (data shown as mean ± SD or as number of cases and percentage n (%)).</p

Structural equation models for the prediction of cognitive state after one year.

<p>Subtext: The numbers on the arcs represent the contribution of each parameter to its neighbor. * <i>p</i><0.05 **<i>p</i><0.001. Abbreviations: ILV, ischemic lesions' volume; WML, white matter lesions; NAWM, normal appearing white matter.</p