Changes in White Matter Microstructure Over 3 Years in People With and Without Stroke.

BACKGROUND AND OBJECTIVES: Cerebral white matter health can be estimated by MRI-derived indices of microstructure. White matter dysfunction is increasingly recognized as a contributor to neurodegenerative disorders affecting cognition and to functional outcomes after stroke. Reduced indices of white matter microstructure have been demonstrated cross-sectionally in stroke survivors compared with stroke-free participants, but longitudinal changes in the structure of white matter after stroke remain largely unexplored. We aimed to characterize white matter micro- and macrostructure over 3 years after stroke and study associations with white matter metrics and cognitive functions. METHODS: Patients with first-ever or recurrent ischemic stroke of any etiology in any vascular territory were compared with stroke-free age- and sex-matched controls. Those diagnosed with hemorrhagic stroke, TIA, venous infarction, or significant medical comorbidities, psychiatric and neurodegenerative disorders, substance abuse, or history of dementia were excluded. Diffusion-weighted MRI data at 3, 12, and 36 months were analyzed using a longitudinal fixel-based analysis, sensitive to fiber tract-specific differences within a voxel. It was used to examine whole-brain white matter degeneration in stroke compared with control participants. We studied microstructural differences in fiber density and macrostructural changes in fiber-bundle cross-section, in relation to cognitive performance. Analyses were performed controlling for age, intracranial volume, and education (family-wise error-corrected p < 0.05, nonparametric testing over 5,000 permutations). RESULTS: We included 71 participants with stroke (age 66 ± 12 years, 22 women) and 36 controls (age 69 ± 5 years, 13 women). We observed extensive white matter structural degeneration across the whole brain, particularly affecting the thalamic, cerebellar, striatal, and superior longitudinal tracts and corpus callosum. Importantly, follow-up regression analyses in 72 predefined tracts showed that the decline in fiber density and cross-section from 3 months to 3 years was associated with worse cognitive performance at 3 years after stroke, especially affecting visuospatial processing, processing speed, language, and recognition memory. DISCUSSION: We conclude that white matter neurodegeneration in ipsi- and contralesional thalamic, striatal, and cerebellar tracts continues to be greater in stroke survivors compared with stroke-free controls. White matter degeneration persists even years after stroke and is associated with poststroke cognitive impairment. TRIAL REGISTRATION INFORMATION: ClinicalTrails.gov NCT02205424.

Mood and Cognitive Trajectories Over the First Year after Mild Ischemic Stroke.

OBJECTIVES: Cognitive and mood dysfunction are major contributors to post-stroke disability. The longer-term trajectories of mood and cognition post-stroke remain unclear, as do which cognitive domains decline, improve, or remain stable after stroke, and in which patients. We aimed to characterize the cognitive trajectories of mild ischemic stroke survivors over one year compared to stroke-free controls, and to investigate whether symptoms of anxiety and depression were associated with cognitive function. MATERIALS AND METHODS: All participants were tested with a neuropsychological test battery at 3-months and 12-months post-stroke, assessing attention/processing speed, memory, visuospatial function, executive function, and language. Anxiety and depression symptomatology were also assessed at both timepoints. RESULTS: Stroke participants (N=126, mean age 68.44 years ±11.83, 87 males, median [Q1, Q3] admission NIHSS=2 [1, 4]) performed worse on cognitive tests and endorsed significantly higher depression and anxiety symptomatology than controls (N=40, mean age=68.82 years ±6.33, 25 males) at both timepoints. Mood scores were not correlated with cognitive performance. Stroke participants' scores trended higher across cognitive domains from 3- to 12-months but statistically significant improvement was only observed on executive function tasks. CONCLUSION: Stroke participants performed significantly worse than controls on all cognitive domains following mild ischemic stroke. Stroke participants only exhibited statistically significant improvement on executive function tasks between 3- and 12- months. Whilst anxiety and depression symptoms were higher in stroke participants, this was not correlated with cognitive performance. Further studies are needed to understand factors underlying cognitive recovery and decline after stroke.

Pre-stroke physical activity and admission stroke severity: A systematic review.

BACKGROUND: Admission stroke severity is an important clinical predictor of stroke outcomes. Pre-stroke physical activity contributes to stroke prevention and may also be associated with reduced stroke severity. Summarizing the evidence to date will inform strategies to reduce burden after stroke. AIMS: To summarize the published evidence for the relationship between pre-stroke physical activity and admission stroke severity and to provide recommendations for future research. SUMMARY OF REVIEW: MEDLINE, Embase, Emcare, CENTRAL, and gray literature databases were searched on 14 February 2020 using search terms related to stroke and pre-stroke physical activity in adult stroke survivors. We screened 8,152 references and assessed 172 full-text references for eligibility. We included seven studies (n = 41,800 stroke survivors). All studies were observational, assessed pre-stroke physical activity using self-reported questionnaires, and assessed admission stroke severity using the National Institute of Health Stroke Scale. Analyses were categorized as the presence of pre-stroke physical activity (four studies) or dose-response (five studies). In three studies, presence of pre-stroke physical activity was associated with milder stroke severity, and no association in one study. Greater pre-stroke physical activity duration and intensity (two studies) or amount (three studies) were associated with milder stroke severity. Studies ranged between moderate to critical risk of bias, primarily due to confounding factors. Pre-stroke physical activity may be associated with reduced risk factors for severe stroke, distal occlusion, smaller infarcts, and shorter time-to-treatment delivery. CONCLUSION: Pre-stroke physical activity may be associated with reduced admission stroke severity. Lack of randomized controlled trials limited causality conclusions. Future research recommendations were provided.

Time for a Systems Biological Approach to Cognitive Aging?-A Critical Review.

The underlying premise of current theories of cognitive decline with age tend to be primarily cognitive or biological explanations, with relatively few theories adequately integrating both aspects. Though literature has also emphasized the importance of several factors that contribute to cognitive aging including: (a) decline in sensory abilities; (b) the effect of motor speed on paper-pencil measures of cognitive speed; (c) the impact of level of education and physical activity; and (d) molecular biological changes that occur with age, these factors have seldom been implicated into any single theoretical model of cognitive aging. Indeed, such an integrated bio-cognitive model of aging has the potential to provide a more comprehensive understanding of attention, perception, learning, and memory across the lifespan. Thus, the aim of this review was to critically evaluate common theories of age-related cognitive decline and highlight the need for a more comprehensive systems neuroscience approach to cognitive aging.

The Contribution of Oculomotor Functions to Rates of Visual Information Processing in Younger and Older Adults.

Oculomotor functions are established surrogate measures of visual attention shifting and rate of information processing, however, the temporal characteristics of saccades and fixations have seldom been compared in healthy educated samples of younger and older adults. Thus, the current study aimed to compare duration of eye movement components in younger (18-25 years) and older (50-81 years) adults during text reading and during object/alphanumeric Rapid Automatic Naming (RAN) tasks. The current study also aimed to examine the contribution of oculomotor functions to threshold time needed for accurate performance on visually-driven cognitive tasks (Inspection Time [IT] and Change Detection [CD]). Results showed that younger adults fixated on individual stimuli for significantly longer than the older participants, while older adults demonstrated significantly longer saccade durations than the younger group. Results also demonstrated that older adults required longer threshold durations (i.e., performed slower) on the visually-driven cognitive tasks, however, the age-group time difference on the CD task was eradicated when the effects of saccade duration were covaried. Thus, these results suggest that age-related cognitive decline is also related to increased duration of saccades and hence, highlights the need to dissociate the age-related motor constraints on the temporal aspects of oculomotor function from visuo-cognitive speed of processing.

The Migraine-Anxiety Comorbidity Among Migraineurs: A Systematic Review.

Background: Migraine is recognized as a neurological condition that is often associated with comorbid psychiatric symptoms such as anxiety, depression, bipolar disorder and/or panic disorder. Though some studies have demonstrated the link between migraine and anxiety disorders, there are no systematic reviews that have been published in this area to summarize the evidence. The aim of the present study is to systematically review the literature associated with comorbidity of migraine and anxiety disorders among migraineurs compared to non-migraineurs. Methods: The present systematic review included population-based, cohort and cross-sectional studies if they were reporting the frequency of migraine with either anxiety or depression as diagnosed by a medical practitioner according to the International Classification of Headache Disorders (ICHD-2/3). Results: Eight eligible studies from 2060 relevant citations were included in the review. All participants were migraine patients from both primary care and outpatient settings, as well as tertiary headache and anxiety centers, and were compared to non-migraineurs. The results of the systematic review showed that there is a strong and consistent relationship between migraine and anxiety. The co-morbidity of co-occurrence for migraine and anxiety has an average OR of 2.33 (2.20-2.47) among the prevalence and cross sectional studies and an average RR of 1.63 (1.37-1.93) for two cohort studies; The major limitations of included studies were small sample sizes and a lack of adjusting of confounding factors. Conclusion: The results highlight the need for inclusion of an anxiety screening tool during initial assessments of migraine patients by medical practitioners and/or physicians and may explain why some anxiolytic medications work better than others for migraine mitigation.

Visual Information Processing in Young and Older Adults.

Decline in information processing with age is well-documented in the scientific literature. However, some discrepancy remains in relation to which cognitive domains are most susceptible to the aging process and which may remain intact. Furthermore, information processing has not been investigated nor considered as a function of affect, familiarity and complexity of tasks in a single experimental study. Thus, the current study investigated rate of visual information processing in 67 young university students (M age = 19.64 years) and 33 educated healthy older adults (M age = 70.33 years), while accounting for depression, anxiety and stress symptoms using the DASS. Rates of visual processing were measured as minimum time of stimulus exposure duration required for correct object recognition on a simple visual task [Inspection Time (IT)], and on a more complex visual cognitive task known as Change Detection (CD)] as well as words per minute on a text reading task (FastaReada). The results demonstrated significantly slower performance by older adults on the IT and CD, but comparable rates of text reading on a semantically more complex, but ecologically valid and familiar visual task that requires organized sequential shifts in attention via eye movements, continuous visual processing, access to working memory and semantic comprehension. The results also demonstrated that affective influences did not play a role in the older adults task performance, and that changes in cognitive domains may begin with older adults being slower to attend to and identify newly appearing familiar objects, as well as slower to encode and embed new information in memory during tasks that require a less practiced/familiar task strategy.

Temporal Aspects of Memory: A Comparison of Memory Performance, Processing Speed and Time Estimation Between Young and Older Adults.

Cognitive abilities are often reported to decline across the lifespan, particularly when assessed with working memory (WM) measures such as the auditory backward digit span and complex N-back tasks. However, some debate still exists regarding which aspects of cognition are most susceptible to the aging process and which may remain intact. Additionally, time estimation, though a complex psychological dimension, is often studied in relative isolation and is particularly neglected in traditional studies of WM, with little research from the viewpoint of retrospective temporal estimation. In particular, research seldom considers whether the ability to accurately estimate time retrospectively, is correlated with performance on traditional memory and processing speed measures in healthy populations. Thus, we chose to investigate performance of comparably educated young and older adult groups on both classical memory tasks including auditory and visual digit spans, N-back, Wechsler Adult Intelligence Scale (WAIS)-based measures of processing speed (i.e., Symbol Search [SS] and Coding [Cod]) and a temporal measure of WM with a focus on retrospective time estimation. Our sample included 66 university students (58 F, 8 M) between the ages of 18-29, and 33 university-educated healthy older adults (25 F, 8 M) between the ages of 60-81. Results indicated that older adults performed significantly worse on auditory but not the visual digit span tasks, as well as on both the SS and Cod, though performed equally well on the N = 1 back task. Results also showed that retrospective time estimation was not significantly different between young and older adults, with both groups substantially underestimating duration of a simple task. Retrospective time estimation was not significantly correlated to any memory or processing speed measure, emphasizing the need for future research into the specific cognitive domains underlying the subjective estimation of a temporal interval.

Cognitive Processing Speed across the Lifespan: Beyond the Influence of Motor Speed.

Traditional neuropsychological measurement of cognitive processing speed with tasks such as the Symbol Search and Coding subsets of the WAIS-IV, consistently show decline with advancing age. This is potentially problematic with populations where deficits in motor performance are expected, i.e., in aging or stroke populations. Thus, the aim of the current study was to explore the contribution of hand motor speed to traditional paper-and-pencil measures of processing speed and to a simple computer-customized non-motor perception decision task, the Inspection Time (IT) task. Participants were 67 young university students aged between 18 and 29 (59 females), and 40 older adults aged between 40 and 81 (31 females) primarily with a similar education profile. As expected, results indicated that age group differences were highly significant on the motor dexterity, Symbol Search and Coding tasks. However, no significant differences or correlations were seen between age groups and the simple visual perception IT task. Furthermore, controlling for motor dexterity did not remove significant age-group differences on the paper-and-pencil measures. This demonstrates that although much of past research into cognitive decline with age is confounded by use of motor reaction times as the operational measure, significant age differences in cognitive processing also exist on more complex tasks. The implications of the results are crucial in the realm of aging research, and caution against the use of traditional WAIS tasks with a clinical population where motor speed may be compromised, as in stroke.