The Influence of Structural Brain Changes on Cognition in the Context of Healthy Aging: Exploring Mediation Effects Through gBAT-The Graphical Brain Association Tool.

The contribution of age-related structural brain changes to the well-established link between aging and cognitive decline is not fully defined. While both age-related regional brain atrophy and cognitive decline have been extensively studied, the specific mediating role of age-related regional brain atrophy on cognitive functions is unclear. This study introduces an open-source software tool with a graphical user interface that streamlines advanced whole-brain mediation analyses, enabling researchers to systematically explore how the brain acts as a mediator in relationships between various behavioral and health outcomes. The tool is showcased by investigating regional brain volume as a mediator to determine the contribution of age-related brain volume loss toward cognition in healthy aging. We analyzed regional brain volumes and cognitive testing data (Montreal Cognitive Assessment [MoCA]) from a cohort of 131 neurologically healthy adult participants (mean age 50 ± 20.8 years, range 20-79, 73% females) drawn from the Aging Brain Cohort Study at the University of South Carolina. Using our open-source tool developed for evaluating brain-behavior associations across the brain and optimized for exploring mediation effects, we conducted a series of mediation analyses using participant age as the predictor variable, total MoCA and MoCA subtest scores as the outcome variables, and regional brain volume as potential mediators. Age-related atrophy within specific anatomical networks was found to mediate the relationship between age and cognition across multiple cognitive domains. Specifically, atrophy in bilateral frontal, parietal, and occipital areas, along with widespread subcortical regions mediated the effect of age on total MoCA scores. Various MoCA subscores were influenced by age through atrophy in distinct brain regions. These involved prefrontal regions, sensorimotor cortex, and parieto-occipital areas for executive function subscores, prefrontal and temporo-occipital regions, along with the caudate nucleus for attention and concentration subscores, frontal and parieto-occipital areas, alongside connecting subcortical areas such as the optic tract for visuospatial subscores and frontoparietal areas for language subscores. Brain-based mediation analysis offers a causal framework for evaluating the mediating role of brain structure on the relationship between age and cognition and provides a more nuanced understanding of cognitive aging than previously possible. By validating the applicability and effectiveness of this approach and making it openly available to the scientific community, we facilitate the exploration of causal mechanisms between variables mediated by the brain.

Diabetes, brain health, and treatment gains in post-stroke aphasia.

In post-stroke aphasia, language improvements following speech therapy are variable and can only be partially explained by the lesion. Brain tissue integrity beyond the lesion (brain health) may influence language recovery and can be impacted by cardiovascular risk factors, notably diabetes. We examined the impact of diabetes on structural network integrity and language recovery. Seventy-eight participants with chronic post-stroke aphasia underwent six weeks of semantic and phonological language therapy. To quantify structural network integrity, we evaluated the ratio of long-to-short-range white matter fibers within each participant's whole brain connectome, as long-range fibers are more susceptible to vascular injury and have been linked to high level cognitive processing. We found that diabetes moderated the relationship between structural network integrity and naming improvement at 1 month post treatment. For participants without diabetes (n = 59), there was a positive relationship between structural network integrity and naming improvement (t = 2.19, p = 0.032). Among individuals with diabetes (n = 19), there were fewer treatment gains and virtually no association between structural network integrity and naming improvement. Our results indicate that structural network integrity is associated with treatment gains in aphasia for those without diabetes. These results highlight the importance of post-stroke structural white matter architectural integrity in aphasia recovery.

Impact of Reducing Fluoroscopy Pulse Rate on Adult Modified Barium Swallow Studies.

Modified Barium Swallow Studies (MBSS) are a critical part of the evaluation, treatment planning, and outcome assessment for persons with swallowing disorders. Since MBSSs use ionizing radiation with associated cancer risks, many clinicians have reduced radiation exposure by reducing the fluoroscopic pulse rate. However, by reducing pulse rate, we also decrease the temporal resolution of MBSSs which has been shown in pilot studies to significantly reduce diagnostic accuracy. Two hundred MBSSs from patients routinely undergoing MBSS as standard of care conducted at 30 pulses per second (pps) using the Modified Barium Swallow Study Impairment Profile (MBSImP™) standardized administration protocol were selected. A stratified sampling method ensured that a full range of swallowing impairments (etiology, type, and severity) was represented. Recordings were down sampled from 30 pps to 15, 7.5, and 4 pps. MBSSs were rated using the MBSImP components and Penetration-Aspiration Scale (PAS) score for each swallow. Percent agreement was calculated across raters for MBSImP and PAS scores by bolus type and volume. The Least-Squares Method was used for hypothesis testing. Statistically significant and clinically meaningful changes in scores of swallowing physiology and penetration/aspiration occurred when reducing pulse rate below 30pps. These changes were evident across bolus types and volumes. Given the impact on diagnostic accuracy and the low radiation risks to adults undergoing MBSSs, reducing pulse rate to 15pps or below is not aligned with the As Low As Reasonably Achievable (ALARA) principle and should not be used as a viable method to reduce radiation exposure from MBSSs.

Language Recovery after Brain Injury: A Structural Network Control Theory Study.

Aphasia recovery after stroke depends on the condition of the remaining, extralesional brain network. Network control theory (NCT) provides a unique, quantitative approach to assess the interaction between brain networks. In this longitudinal, large-scale, whole-brain connectome study, we evaluated whether controllability measures of language-related regions are associated with treated aphasia recovery. Using probabilistic tractography and controlling for the effects of structural lesions, we reconstructed whole-brain diffusion tensor imaging (DTI) connectomes from 68 individuals (20 female, 48 male) with chronic poststroke aphasia who completed a three-week language therapy. Applying principles of NCT, we computed regional (1) average and (2) modal controllability, which decode the ability of a region to (1) spread control input through the brain network and (2) to facilitate brain state transitions. We tested the relationship between pretreatment controllability measures of 20 language-related left hemisphere regions and improvements in naming six months after language therapy using multiple linear regressions and a parsimonious elastic net regression model with cross-validation. Regional controllability of the inferior frontal gyrus (IFG) pars opercularis, pars orbitalis, and the anterior insula were associated with treatment outcomes independently of baseline aphasia severity, lesion volume, age, education, and network size. Modal controllability of the IFG pars opercularis was the strongest predictor of treated aphasia recovery with cross-validation and outperformed traditional graph theory, lesion load, and demographic measures. Regional NCT measures can reflect the status of the residual language network and its interaction with the remaining brain network, being able to predict language recovery after aphasia treatment.SIGNIFICANCE STATEMENT Predicting and understanding language recovery after brain injury remains a challenging, albeit a fundamental aspect of human neurology and neuroscience. In this study, we applied network control theory (NCT) to fully harness the concept of brain networks as dynamic systems and to evaluate their interaction. We studied 68 stroke survivors with aphasia who underwent imaging and longitudinal behavioral assessments coupled with language therapy. We found that the controllability of the inferior frontal regional network significantly predicted recovery in language production six months after treatment. Importantly, controllability outperformed traditional demographic, lesion, and graph-theoretical measures. Our findings shed light on the neurobiological basis of human language and can be translated into personalized rehabilitation approaches.

High b-value diffusion tractography: Abnormal axonal network organization associated with medication-refractory epilepsy.

Diffusion magnetic resonance imaging (dMRI) tractography has played a critical role in characterizing patterns of aberrant brain network reorganization among patients with epilepsy. However, the accuracy of dMRI tractography is hampered by the complex biophysical properties of white matter tissue. High b-value diffusion imaging overcomes this limitation by better isolating axonal pathways. In this study, we introduce tractography derived from fiber ball imaging (FBI), a high b-value approach which excludes non-axonal signals, to identify atypical neuronal networks in patients with epilepsy. Specifically, we compared network properties obtained from multiple diffusion tractography approaches (diffusion tensor imaging, diffusion kurtosis imaging, FBI) in order to assess the pathophysiological relevance of network rearrangement in medication-responsive vs. medication-refractory adults with focal epilepsy. We show that drug-resistant epilepsy is associated with increased global network segregation detected by FBI-based tractography. We propose exploring FBI as a clinically feasible alternative to quantify topological changes that could be used to track disease progression and inform on clinical outcomes.

Radiation Effective Doses to Adults Undergoing Modified Barium Swallow Studies.

Modified Barium Swallow Studies (MBSSs) are important tests to aid the diagnosis of swallowing impairment and guide treatment planning. Since MBSSs use ionizing radiation, it is important to understand the radiation exposure associated with the exam. This study reports the average radiation dose in routine clinical MBSSs, to aid the evidence-based decision-making of clinical providers and patients. We examined the MBSSs of 200 consecutive adult patients undergoing clinically indicated exams and used kilovoltage (kV) and Kerma Area Product to calculate the effective dose. While 100% of patients underwent the exam in the lateral projection, 72% were imaged in the upper posterior-anterior (PA) projection and approximately 25% were imaged in the middle and lower PA projection. Average kVs were 63 kV, 77 kV, 78.3 kV, and 94.3 kV, for the lateral, upper, middle, and lower PA projections, respectively. The average effective dose per exam was 0.32 ± 0.23 mSv. These results categorize a typical adult MBSS as a low dose examination. This value serves as a general estimate for adults undergoing MBSSs and can be used to compare other sources of radiation (environmental and medical) to help clinicians and patients assess the risks of conducting an MBSS. The distinction of MBSS as a low dose exam will assuage most clinician's fears, allowing them to utilize this tool to gather clinically significant information about swallow function. However, as an X-ray exam that uses ionizing radiation, the principles of ALARA and radiation safety must still be applied.

Neural structures supporting spontaneous and assisted (entrained) speech fluency.

Non-fluent speech is one of the most common impairments in post-stroke aphasia. The rehabilitation of non-fluent speech in aphasia is particularly challenging as patients are rarely able to produce and practice fluent speech production. Speech entrainment is a behavioural technique that enables patients with non-fluent aphasia to speak fluently. However, its mechanisms are not well understood and the level of improved fluency with speech entrainment varies among individuals with non-fluent aphasia. In this study, we evaluated the behavioural and neuroanatomical factors associated with better speech fluency with the aid of speech entrainment during the training phase of speech entrainment. We used a lesion-symptom mapping approach to define the relationship between chronic stroke location on MRI and the number of different words per second produced during speech entrainment versus picture description spontaneous speech. The behavioural variable of interest was the speech entrainment/picture description ratio, which, if ≥1, indicated an increase in speech output during speech entrainment compared to picture description. We used machine learning (shallow neural network) to assess the statistical significance and out-of-sample predictive accuracy of the neuroanatomical model, and its regional contributors. We observed that better assisted speech (higher speech entrainment/picture description ratio) was achieved by individuals who had preservation of the posterior middle temporal gyrus, inferior fronto-occipital fasciculus and uncinate fasciculus, while exhibiting lesions in areas typically associated with non-fluent aphasia, such as the superior longitudinal fasciculus, precentral, inferior frontal, supramarginal and insular cortices. Our findings suggest that individuals with dorsal stream damage but preservation of ventral stream structures are more likely to achieve more fluent speech with the aid of speech entrainment compared to spontaneous speech. This observation provides insight into the mechanisms of non-fluent speech in aphasia and has potential implications for future research using speech entrainment for rehabilitation of non-fluent aphasia.

Long-range fibre damage in small vessel brain disease affects aphasia severity.

We sought to determine the underlying pathophysiology relating white matter hyperintensities to chronic aphasia severity. We hypothesized that: (i) white matter hyperintensities are associated with damage to fibres of any length, but to a higher percentage of long-range compared to mid- and short-range intracerebral white matter fibres; and (ii) the number of long-range fibres mediates the relationship between white matter hyperintensities and chronic post-stroke aphasia severity. We measured the severity of periventricular and deep white matter hyperintensities and calculated the number and percentages of short-, mid- and long-range white matter fibres in 48 individuals with chronic post-stroke aphasia. Correlation and mediation analyses were performed to assess the relationship between white matter hyperintensities, connectome fibre-length measures and aphasia severity as measured with the aphasia quotient of the Western Aphasia Battery-Revised (WAB-AQ). We found that more severe periventricular and deep white matter hyperintensities correlated with a lower proportion of long-range fibres (r = -0.423, P = 0.003 and r = -0.315, P = 0.029, respectively), counterbalanced by a higher proportion of short-range fibres (r = 0.427, P = 0.002 and r = 0.285, P = 0.050, respectively). More severe periventricular white matter hyperintensities also correlated with a lower proportion of mid-range fibres (r = -0.334, P = 0.020), while deep white matter hyperintensities did not correlate with mid-range fibres (r = -0.169, P = 0.250). Mediation analyses revealed: (i) a significant total effect of periventricular white matter hyperintensities on WAB-AQ (standardized beta = -0.348, P = 0.008); (ii) a non-significant direct effect of periventricular white matter hyperintensities on WAB-AQ (P > 0.05); (iii) significant indirect effects of more severe periventricular white matter hyperintensities on worse aphasia severity mediated in parallel by fewer long-range fibres (effect = -6.23, bootstrapping: standard error = 2.64, 95%CI: -11.82 to -1.56) and more short-range fibres (effect = 4.50, bootstrapping: standard error = 2.59, 95%CI: 0.16 to 10.29). We conclude that small vessel brain disease seems to affect chronic aphasia severity through a change of the proportions of long- and short-range fibres. This observation provides insight into the pathophysiology of small vessel brain disease, and its relationship with brain health and chronic aphasia severity.

Radiation Risks to Adult Patients Undergoing Modified Barium Swallow Studies.

Modified Barium Swallow Studies (MBSSs) are a fluoroscopic exam that exposes patients to ionizing radiation. Even though radiation exposure from MBSSs is relatively small, it is necessary to understand the excess cancer risk to the patient, in order to ensure a high benefit-to-risk ratio from the exam. This investigation was aimed at estimating the excess radiation risks during MBSSs. We examined 53 adult MBSSs performed using the full Modified Barium Swallow Impairment Profile (MBSImP) protocol. For each exam, the radiation dose (in terms of dose area product), patient age, and sex was recorded. Using published methodology, we determined the effective dose and organ specific dose then used BEIR VII data to calculate the excess cancer incidence related to radiation exposure from MBSSs in adults. Excess cancer incidence risks due to MBSSs were 11 per million exposed patients for 20-year-old males, 32 per million exposed patients for 20-year-old females, 4.9 per million exposed patients for 60-year-old males, and 7.2 per million exposed patients for 60-year-old females. Radiation exposure to the thyroid, lung, and red bone marrow contributed over 90% of the total cancer incidence risk. For the 20-year-old males, the excess cancer incidence risk is 4.7%/Sv, which is reduced to 1.0%/Sv in the 80-year-olds. For the 20-year-old females, the excess cancer incidence risk is 14%/Sv, which is reduced to 1.3%/Sv for 80-year-olds. Overall, the risk per unit effective dose from MBSSs is lower than the risk estimates for uniform whole-body irradiation. Patient age is the most important determinant of patient cancer risk from MBSSs.

Factors Influencing Oral Intake Improvement and Feeding Tube Dependency in Patients with Poststroke Dysphagia.

OBJECTIVE: To assess ischemic stroke patients regarding the relationship between lesion locations, swallowing impairment, medical and demographic factors and (1) oral intake improvement and (2) feeding tube dependency at discharge from their acute hospital stay. METHODS: We conducted an exploratory, retrospective observational longitudinal cohort study of acute, first-ever, ischemic stroke patients. Patients who had an initial nonoral feeding recommendation from a speech and language pathologist and who underwent a modified barium swallow study within their hospital stay were included. Oral intake status was measured with the Functional Oral Intake Scale (FOIS) as the change in FOIS during the hospital stay and as feeding tube dependency at hospital discharge. Associations were assessed with multiple linear regression modeling controlling for age, comorbidities, and hospital length of stay. RESULTS: We included 44 stroke patients. At hospital discharge, 93% of patients had oral intake restrictions and 30% were feeding tube dependent. Following multiple linear regression modeling, age, damage to the left superior frontal gyrus, dorsal anterior cingulate gyrus, hypothalamus, and nucleus accumbens were significant predictors for FOIS change. Feeding tube dependency showed no significant associations with any prognostic variables when controlling for confounders. CONCLUSIONS: The vast majority of patients with an initial nonoral feeding recommendation are discharged with oral intake restrictions indicating a continued need for swallowing assessments and treatment after discharge. Lesion locations associated with motivation, reward, and drive to consume food as well as swallowing impairment, higher age, and more comorbidities were related to less oral intake improvement.

Hospital Readmissions of Stroke Patients with Percutaneous Endoscopic Gastrostomy Feeding Tubes.

OBJECTIVES: A critical mission of acute care hospitals is to reduce hospital readmissions to improve patient care and avoid monetary penalties. We speculated that stroke patients with enteral tube feeding are high-risk patients and sought to evaluate their hospital readmissions. METHODS: We analyzed archival hospital billing data from stroke patients discharged from acute care hospitals in Florida in 2012 for 30- and 60-day readmission rates, 30-day readmission rates by discharge destination, most frequent primary readmission diagnoses, and predictors of 30-day readmissions. We conducted univariate and multivariable logistic regression analyses. RESULTS: We analyzed 26,774 discharge records. Within 30 days after discharge, 21.06% (N = 299) of stroke patients with percutaneous endoscopic gastrostomy (PEG) tube placement were rehospitalized. Of those readmissions, 11.71% (N = 35) were preventable. Among stroke patients with a PEG tube placement, 53.80% were discharged to skilled nursing facilities and 27.88% were rehospitalized within 30 days. Septicemia was the most frequent primary readmission diagnosis. Comorbidities, stroke type, length of hospital stay, and discharge destinations were predictive for 30-day readmissions (area under the receiver operating characteristic curve was .81). CONCLUSIONS: Stroke patients with a PEG tube placement during their index hospital stay are twice as likely to be readmitted within 30 days compared to stroke patients without PEG tube placements. The primary readmission diagnosis for some patients was directly linked to PEG tube complications. We have identified risk factors that can be used to focus resources for readmission prevention.

Practice Patterns of Percutaneous Endoscopic Gastrostomy Tube Placement in Acute Stroke: Are the Guidelines Achievable?

OBJECTIVES: Our objectives were to evaluate trends in percutaneous endoscopic gastrostomy (PEG) tube placement rate and timing in acute stroke patients. We hypothesized that noncompliance with clinical practice guidelines for timing of tube placement and an increase in placement occurred because of a decrease in length of hospital stay. METHODS: We conducted a retrospective observational study of archival hospital billing data from the Florida state inpatient healthcare cost and utilization project database from 2001 to 2012 for patients with a primary diagnosis of stroke. Outcome measures were timing of PEG tube placements by year (2006-2012), rate of placements by year (2001-2012), and length of hospital stay. Univariate analyses and simple and multivariable logistic regression analyses were conducted. RESULTS: The timing of gastrostomy tube placement remained stable with a median of 7 days post admission from 2006 through 2012. The proportion of tubes that were placed at or after 14 days and thereby met the guideline recommendations varied from 14.09% in 2006 to 13.41% in 2012. The rate of tube placement in stroke patients during the acute hospital stay decreased significantly by 25% from 6.94% in 2001 to 5.22% in 2012 (P < .0001). The length of hospital stay for all stroke patients decreased over the study period (P < .0001). CONCLUSIONS: The vast majority of PEG tube placements happen earlier than clinical practice guidelines recommend. Over the study period, the rate of tubes placed in stroke patients decreased during the acute hospital stay despite an overall reduced length of stay.

Under pressure: the interplay of hypertension and white matter hyperintensities with cognition in chronic stroke aphasia.

While converging research suggests that increased white matter hyperintensity load is associated with poorer cognition, and the presence of hypertension is associated with increased white matter hyperintensity load, the relationship among hypertension, cognition and white matter hyperintensities is not well understood. We sought to determine the effect of white matter hyperintensity burden on the relationship between hypertension and cognition in individuals with post-stroke aphasia, with the hypothesis that white matter hyperintensity load moderates the relationship between history of hypertension and cognitive function. Health history, Fazekas scores for white matter hyperintensities and Wechsler Adult Intelligence Scale Matrix Reasoning subtest scores for 79 people with aphasia collected as part of the Predicting Outcomes of Language Rehabilitation study at the Center for the Study of Aphasia Recovery at the University of South Carolina and the Medical University of South Carolina were analysed retrospectively. We found that participants with a history of hypertension had increased deep white matter hyperintensity severity (P < 0.001), but not periventricular white matter hyperintensity severity (P = 0.116). Moderation analysis revealed that deep white matter hyperintensity load moderates the relationship between high blood pressure and Wechsler Adult Intelligence Scale scores when controlling for age, education, aphasia severity and lesion volume. The interaction is significant, showing that a history of high blood pressure and severe deep white matter hyperintensities together are associated with poorer Matrix Reasoning scores. The overall model explains 41.85% of the overall variation in Matrix Reasoning score in this group of participants. These findings underscore the importance of considering cardiovascular risk factors in aphasia treatment, specifically hypertension and its relationship to brain health in post-stroke cognitive function.

Dissociating reading and auditory comprehension in persons with aphasia.

Language comprehension is often affected in individuals with post-stroke aphasia. However, deficits in auditory comprehension are not fully correlated with deficits in reading comprehension and the mechanisms underlying this dissociation remain unclear. This distinction is important for understanding language mechanisms, predicting long-term impairments and future development of treatment interventions. Using comprehensive auditory and reading measures from a large cohort of individuals with aphasia, we evaluated the relationship between aphasia type and reading comprehension impairments, the relationship between auditory versus reading comprehension deficits and the crucial neuroanatomy supporting the dissociation between post-stroke reading and auditory deficits. Scores from the Western Aphasia Battery-Revised from 70 participants with aphasia after a left-hemisphere stroke were utilized to evaluate both reading and auditory comprehension of linguistically equivalent stimuli. Repeated-measures and univariate ANOVA were used to assess the relationship between auditory comprehension and aphasia types and correlations were employed to test the relationship between reading and auditory comprehension deficits. Lesion-symptom mapping was used to determine the dissociation of crucial brain structures supporting reading comprehension deficits controlling for auditory deficits and vice versa. Participants with Broca's or global aphasia had the worst performance on reading comprehension. Auditory comprehension explained 26% of the variance in reading comprehension for sentence completion and 44% for following sequential commands. Controlling for auditory comprehension, worse reading comprehension performance was independently associated with damage to the inferior temporal gyrus, fusiform gyrus, posterior inferior temporal gyrus, inferior occipital gyrus, lingual gyrus and posterior thalamic radiation. Auditory and reading comprehension are only partly correlated in aphasia. Reading is an integral part of daily life and directly associated with quality of life and functional outcomes. This study demonstrated that reading performance is directly related to lesioned areas in the boundaries between visual association regions and ventral stream language areas. This behavioural and neuroanatomical dissociation provides information about the neurobiology of language and mechanisms for potential future treatment interventions.

Long-range white matter fibres and post-stroke verbal and non-verbal cognition.

Among stroke survivors, linguistic and non-linguistic impairments exhibit substantial inter-individual variability. Stroke lesion volume and location do not sufficiently explain outcomes, and the neural mechanisms underlying the severity of aphasia or non-verbal cognitive deficits remain inadequately understood. Converging evidence supports the idea that white matter is particularly susceptible to ischaemic injury, and long-range fibres are commonly associated with verbal and non-verbal function. Here, we investigated the relationship among post-stroke aphasia severity, cognition, and white matter integrity. Eighty-seven individuals in the chronic stage of stroke underwent diffusion MRI and behavioural testing, including language and cognitive measures. We used whole-brain structural connectomes from each participant to calculate the ratio of long-range fibres to short-range fibres. We found that a higher proportion of long-range fibres was associated with lower aphasia severity, more accurate picture naming, and increased performance on non-verbal semantic memory/processing and non-verbal reasoning while controlling for lesion volume, key damage areas, age, and years post stroke. Our findings corroborate the hypothesis that, after accounting for age and lesion anatomy, inter-individual differences in post-stroke aphasia severity, verbal, and non-verbal cognitive outcomes are related to the preservation of long-range white matter fibres beyond the lesion.

Regional brain aging: premature aging of the domain general system predicts aphasia severity.

Premature brain aging is associated with poorer cognitive reserve and lower resilience to injury. When there are focal brain lesions, brain regions may age at different rates within the same individual. Therefore, we hypothesize that reduced gray matter volume within specific brain systems commonly associated with language recovery may be important for long-term aphasia severity. Here we show that individuals with stroke aphasia have a premature brain aging in intact regions of the lesioned hemisphere. In left domain-general regions, premature brain aging, gray matter volume, lesion volume and age were all significant predictors of aphasia severity. Increased brain age following a stroke is driven by the lesioned hemisphere. The relationship between brain age in left domain-general regions and aphasia severity suggests that degradation is possible to specific brain regions and isolated aging matters for behavior.

Brain health imaging markers, post-stroke aphasia and Cognition: A scoping review.

For the past decade, brain health has been an emerging line of scientific inquiry assessing the impact of age-related neurostructural changes on cognitive decline and recovery from brain injury. Typically, compromised brain health is attributed to the presence of small vessel disease (SVD) and brain tissue atrophy, which are represented by various neuroimaging features. However, to date, the relationship between brain health markers and chronic aphasia severity remains unclear. Thus, the goal of this scoping review was to assess the current body of evidence regarding the relationship between SVD-related brain health biomarkers and post-stroke aphasia and cognition. In all, 187 articles were identified from 3 databases, of which 16 articles met the criteria for inclusion. Among these studies, 11 focused on cognition rather than aphasia, while 2 investigated both. Of the 10 studies that used white matter hyperintensities (WMHs) as an indicator of SVD severity, 8 studies (80%) demonstrated a relationship between WMH load and worse cognition in stroke patients. Interestingly, among the studies that specifically investigated aphasia, all 5 studies (100%) demonstrated a relationship between SVD and worse language performance. They also indicated that factors other than brain health (e.g., lesion, age, time post onset) played an important role in determining aphasia severity at a single timepoint. These findings suggest that brain health is likely a crucial factor in the context of aphasia recovery, possibly indicating the necessity of cognitive reserve thresholds for the multimodal cognitive demands associated with language recovery. While SVD and structural brain health are not commonly considered as predictors of aphasia severity, more comprehensive models incorporating brain health have the potential to improve prognosis of post-stroke cognitive and language deficits. Given the variability in the existing literature, a uniform grading system for overall SVD would be beneficial for future research on the mechanisms related to brain networks and neuroplasticity, and their translational impact.

White matter hyperintensity load mediates the relationship between age and cognition.

To elucidate the relationship between age and cognitive decline, it is important to consider structural brain changes such as white matter hyperintensities (WMHs), which are common in older age and may affect behavior. Therefore, we aimed to investigate if WMH load is a mediator of the relationship between age and cognitive decline. Healthy participants (N = 166, 20-80 years) completed the Montreal Cognitive Assessment (MoCA). WMHs were manually delineated on FLAIR scans. Mediation analysis was conducted to determine if WMH load mediates the relationship between age and cognition. Older age was associated with worse cognition (p < 0.001), but this was an indirect effect: older participants had more WMHs, and, in turn, increased WMH load was associated with worse MoCA scores. WMH load mediates the relationship between age and cognitive decline. Importantly, this relationship was not moderated by age (i.e., increased WMH severity is associated with poorer MoCA scores irrespective of age). Across all ages, high cholesterol was associated with increased WMH severity.

Dynamic network properties of the superior temporal gyrus mediate the impact of brain age gap on chronic aphasia severity.

Brain structure deteriorates with aging and predisposes an individual to more severe language impairments (aphasia) after a stroke. However, the underlying mechanisms of this relation are not well understood. Here we use an approach to model brain network properties outside the stroke lesion, network controllability, to investigate relations among individualized structural brain connections, brain age, and aphasia severity in 93 participants with chronic post-stroke aphasia. Controlling for the stroke lesion size, we observe that lower average controllability of the posterior superior temporal gyrus (STG) mediates the relation between advanced brain aging and aphasia severity. Lower controllability of the left posterior STG signifies that activity in the left posterior STG is less likely to yield a response in other brain regions due to the topological properties of the structural brain networks. These results indicate that advanced brain aging among individuals with post-stroke aphasia is associated with disruption of dynamic properties of a critical language-related area, the STG, which contributes to worse aphasic symptoms. Because brain aging is variable among individuals with aphasia, our results provide further insight into the mechanisms underlying the variance in clinical trajectories in post-stroke aphasia.

Different aspects of hand grip performance associated with structural connectivity of distinct sensorimotor networks in chronic stroke.

Knowledge regarding the neural origins of distinct upper extremity impairments may guide the choice of interventions to target neural structures responsible for specific impairments. This cross-sectional pilot study investigated whether different brain networks explain distinct aspects of hand grip performance in stroke survivors. In 22 chronic stroke survivors, hand grip performance was characterized as grip strength, reaction, relaxation times, and control of grip force magnitude and direction. In addition, their brain structural connectomes were constructed from diffusion tensor MRI. Prominent networks were identified based on a two-step factor analysis using the number of streamlines among brain regions relevant to sensorimotor function. We used regression models to estimate the predictive value of sensorimotor network connectivity for hand grip performance measures while controlling for stroke lesion volumes. Each hand grip performance measure correlated with the connectivity of distinct brain sensorimotor networks. These results suggest that different brain networks may be responsible for different aspects of hand grip performance, which leads to varying clinical presentations of upper extremity impairment following stroke. Understanding the brain network correlates for different hand grip performances may facilitate the development of personalized rehabilitation interventions to directly target the responsible brain network for specific impairments in individual patients, thus improving outcomes.