Presence Of White Matter Hyperintensities Research Articles

Characterizing upper extremity fine motor function in the presence of white matter hyperintensities: A 7 T MRI cross-sectional study in older adults

BackgroundWhite matter hyperintensities (WMH) are a prevalent radiographic finding in the aging brain studies. Research on WMH association with motor impairment is mostly focused on the lower-extremity function and further investigation on the upper-extremity is needed. How different degrees of WMH burden impact the network of activation recruited during upper limb motor performance could provide further insight on the complex mechanisms of WMH pathophysiology and its interaction with aging and neurological disease processes. Methods40 healthy elderly subjects without a neurological/psychiatric diagnosis were included in the study (16F, mean age 69.3 years). All subjects underwent ultra-high field 7 T MRI including structural and finger tapping task-fMRI. First, we quantified the WMH lesion load and its spatial distribution. Secondly, we performed a data-driven stratification of the subjects according to their periventricular and deep WMH burdens. Thirdly, we investigated the distribution of neural recruitment and the corresponding activity assessed through BOLD signal changes among different brain regions for groups of subjects. We clustered the degree of WMH based on location, numbers, and volume into three categories; ranging from mild, moderate, and severe. Finally, we explored how the spatial distribution of WMH, and activity elicited during task-fMRI relate to motor function, measured with the 9-Hole Peg Test. ResultsWithin our population, we found three subgroups of subjects, partitioned according to their periventricular and deep WMH lesion load. We found decreased activity in several frontal and cingulate cortex areas in subjects with a severe WMH burden. No statistically significant associations were found when performing the brain-behavior statistical analysis for structural or functional data. ConclusionWMH burden has an effect on brain activity during fine motor control and the activity changes are associated with varying degrees of the total burden and distributions of WMH lesions. Collectively, our results shed new light on the potential impact of WMH on motor function in the context of aging and neurodegeneration.

Suboptimal Sleep Duration Is Associated With Poorer Neuroimaging Brain Health Profiles in Middle-Aged Individuals Without Stroke or Dementia.

The American Heart Association's Life's Simple 7, a public health construct capturing key determinants of cardiovascular health, became the Life's Essential 8 after the addition of sleep duration. The authors tested the hypothesis that suboptimal sleep duration is associated with poorer neuroimaging brain health profiles in asymptomatic middle-aged adults. The authors conducted a prospective magnetic resonance neuroimaging study in middle-aged individuals without stroke or dementia enrolled in the UK Biobank. Self-reported sleep duration was categorized as short (<7 hours), optimal (7-<9 hours), or long (≥9 hours). Evaluated neuroimaging markers included the presence of white matter hyperintensities (WMHs), volume of WMH, and fractional anisotropy, with the latter evaluated as the average of 48 white matter tracts. Multivariable logistic and linear regression models were used to test for an association between sleep duration and these neuroimaging markers. The authors evaluated 39 771 middle-aged individuals. Of these, 28 912 (72.7%) had optimal, 8468 (21.3%) had short, and 2391 (6%) had long sleep duration. Compared with optimal sleep, short sleep was associated with higher risk of WMH presence (odds ratio, 1.11 [95% CI, 1.05-1.18]; P<0.001), larger WMH volume (beta=0.06 [95% CI, 0.04-0.08]; P<0.001), and worse fractional anisotropy profiles (beta=-0.04 [95% CI, -0.06 to -0.02]; P=0.001). Compared with optimal sleep, long sleep duration was associated with larger WMH volume (beta=0.04 [95% CI, 0.01-0.08]; P=0.02) and worse fractional anisotropy profiles (beta=-0.06 [95% CI, -0.1 to -0.02]; P=0.002), but not with WMH presence (P=0.6). Among middle-aged adults without stroke or dementia, suboptimal sleep duration is associated with poorer neuroimaging brain health profiles. Because these neuroimaging markers precede stroke and dementia by several years, these findings are consistent with other findings evaluating early interventions to improve this modifiable risk factor.

Regional white matter hyperintensity volume predicts persistent cognitive impairment in acute lacunar infarct patients.

White matter hyperintensity (WMH) is often described in acute lacunar stroke (ALS) patients. However, the specific relationship between regional WMH volume and persistent cognitive impairment remains unclear. We enrolled patients with ALS who were hospitalized at the First Affiliated Hospital of Soochow University between January 2020 and November 2022. All patients were assessed for global cognitive function using the Montreal Cognitive Assessment (MoCA) scale at 14 ± 2 days and 6 months after the onset of ALS. Manifestations of chronic cerebral small vessel disease (CSVD) were assessed via MRI scan. The distributions of regional WMH were segmented, and their relationship with cognitive impairment was evaluated. A total of 129 patients were enrolled. Baseline frontal WMH volume (OR = 1.18, P = 0.04) was an independent risk factor for long-term cognitive impairment after ALS. Furthermore, the presence of WMH at the genu of the corpus callosum (GCC) at baseline (OR = 3.1, P = 0.033) was strongly associated with persistent cognitive decline. Multivariable logistic regression analysis showed that depression (OR = 6.252, P = 0.029), NIHSS score (OR = 1.24, P = 0.011), and albumin at admission (OR = 0.841, P = 0.032) were also important determinants of long-term cognitive impairment after ALS. Our study found that WMH, especially frontal WMH volume and the presence of WMH at the GCC at baseline, independently contributed to long-term cognitive decline in ALS patients. This study provides new evidence of the clinical relationship between regional WMH volume and cognitive impairment in ALS patients.

Independent external validation of a stroke recurrence score in patients with embolic stroke of undetermined source

BackgroundEmbolic stroke of undetermined source (ESUS) accounts for a substantial proportion of ischaemic strokes. A stroke recurrence score has been shown to predict the risk of recurrent stroke in patients with ESUS based on a combination of clinical and imaging features. This study aimed to externally validate the performance of the ESUS recurrence score using data from a randomized controlled trial.MethodsThe validation dataset consisted of eligible stroke patients with available magnetic resonance imaging (MRI) data enrolled in the PreDAFIS sub-study of the MonDAFIS study. The score was calculated using three variables: age (1 point per decade after 35 years), presence of white matter hyperintensities (2 points), and multiterritorial ischaemic stroke (3 points). Patients were assigned to risk groups as described in the original publication. The model was evaluated using standard discrimination and calibration methods.ResultsOf the 1054 patients, 241 (22.9%) were classified as ESUS. Owing to insufficient MRI quality, three patients were excluded, leaving 238 patients (median age 65.5 years [IQR 20.75], 39% female) for analysis. Of these, 30 (13%) patients experienced recurrent ischaemic stroke or transient ischemic attack (TIA) during a follow-up period of 383 patient-years, corresponding to an incidence rate of 7.8 per 100 patient-years (95% CI 5.3–11.2). Patients with an ESUS recurrence score value of ≥ 7 had a 2.46 (hazard ratio (HR), 95% CI 1.02–5.93) times higher risk of stroke recurrence than patients with a score of 0–4. The cumulative probability of stroke recurrence in the low-(0–4), intermediate-(5–6), and high-risk group (≥ 7) was 9%, 13%, and 23%, respectively (log-rank test, χ2 = 4.2, p = 0.1).ConclusionsThis external validation of a published scoring system supports a threshold of ≥ 7 for identifying ESUS patients at high-risk of stroke recurrence. However, further adjustments may be required to improve the model’s performance in independent cohorts. The use of risk scores may be helpful in guiding extended diagnostics and further trials on secondary prevention in patients with ESUS.Trial registration: Clinical Trials, NCT02204267. Registered 30 July 2014, https://clinicaltrials.gov/ct2/show/NCT02204267.

Correlation between lenticulostriate arteries and white matter microstructure changes in patients with cerebral small vessel disease.

To explore the correlation between the number of lenticulostriate arteries (LSAs) and the white matter features in cerebral small vessel diseases (CSVD) by 3T magnetic resonance imaging (MRI). Seventy-one patients with diagnoses of CSVD were prospectively enrolled to undergo 3T MRI examination, including high-resolution vascular wall imaging (VWI) and diffusion tensor imaging (DTI). The LSAs were observed and counted on VWI, and the patients were divided into three groups according to the LSA counts. The presence of white matter hyperintensities (WMHs), lacunes, cerebral microbleeds (CMBs), and enlarged perivascular spaces (EPVS) was assessed in each patient, and a composite CSVD score was calculated. Periventricular and deep white matter hyperintensity (PVWMH, DWMH) volume ratios were obtained based on automatic segmentation. Fractional anisotropy (FA) and mean diffusivity (MD) were processed by using tract-based spatial statistics (TBSS) analysis. These parameters were compared among the three groups. Correlations between the LSA counts and white matter features were also analyzed. There were differences in WMHs (P = 0.001), CMBs (P < 0.001), EPVS (P = 0.017), composite CSVD scores (P < 0.001), PVWMH volume ratios (P = 0.001), DWMH volume ratios (P < 0.001), global FA (P = 0.001), and global MD (P = 0.002) among the three groups. There were correlations between the LSA counts and WMHs (r = -0.45, P < 0.001), CMBs (r = -0.44, P < 0.001), EPVS (r = -0.28, P = 0.020), the composite CSVD score (r = -0.52, P < 0.001), DWMH volume ratio (r = -0.47, P < 0.001), PWMH volume ratio (r = -0.34, P = 0.004), global FA (r = 0.36, P = 0.002), and global MD (r = -0.33, P = 0.005). Diabetes mellitus (OR 3.36, 95% CI 1.06-10.63; P = 0.039) and increased DWMH volume ratios (OR 1.04, 95% CI 1.00-1.08; P = 0.048) were independent risk factors for a decrease in LSA counts. TBSS analysis showed differences among the three groups in global FA and MD after adjusting for age and sex (P < 0.05). The LSA counts was associated with white matter microstructure changes in CSVD and has the potential to represent the extent of subcortical microvascular damage in CSVD patients.

White matter hyperintensities in migraine are not mediated by a dysfunction of the glymphatic system-A diffusion tensor imaging magnetic resonance imaging study.

We assessed whether brain magnetic resonance imaging (MRI) markers of glymphatic function are altered in patients with migraine and brain white matter hyperintensities (WMHs). The glymphatic system is responsible for the outflow of waste products from the brain. An impaired glymphatic system has been associated with WMH; however, this impairment has not been shown in patients with migraine. The present cross-sectional study included consecutive patients with migraine from a single tertiary headache center. Glymphatic function was assessed by measuring the diffusion tensor imaging along the perivascular space (DTI-ALPS) technique, resulting in an index value. WMHs were assessed and quantified by using the Scheltens semi-quantitative score. We included 147 patients (120 women [81.6%]) with a median (interquartile range [IQR]) age of 45 (36-50) years. In all, 74 (50.3%) patients had WMHs. The median (IQR) ALPS index was similar in patients with WMHs compared with those without, at 2.658 (2.332-3.199) versus 2.563 (2.222-3.050) (p = 0.344). The Scheltens score did not correlate with ALPS index (rho = 0.112, p = 0.268). Our results suggest that the presence of WMHs is not associated with an impairment in the glymphatic system in patients with migraine. Although negative and worthy of further confirmation, our finding has implications for the understanding of the nature of WMH in patients with migraine.

Atypical White Matter Hyperintensities Markedly Impact Plasma Neurofilament Light Chain Variability in GRN Patients.

GRN mutations, causing frontotemporal dementia, can be associated with atypical white matter hyperintensities (WMH). We hypothesized that the presence of WMH may impact neurofilament light chain (NfL) levels, markers of neuroaxonal damage. We analyzed plasma NfL in 20 GRN patients and studied their association to visually-scored WMH burden. The 12 patients displaying atypical WMH had significantly higher NfL levels (98.4±34.9 pg/mL) than those without WMH (47.2±29.4 pg/mL, p = 0.003), independently from age, disease duration and Fazekas-Schmidt grade. NfL correlated with WMH burden (rho = 0.55, p = 0.01). This study prompts considering WMH burden as a variability factor when evaluating NfL levels in GRN patients.

Analysis of Gray Matter Volume (GMV) and White Matter Hyperintensity (WMH) in Ischemic Stroke Patients with Fluid Attenuated Inversion Recovery (FLAIR) Imaging

Stroke is a serious health problem faced by almost all over the world. The occurrence of ischemic stroke could affect the gray matter volume (GMV) in the human brain. In Magnetic Resonance imaging of an ischemic stroke with a FLAIR sequence, a white lesion known as the white matter hyperintensity (WMH) is often found. We studied correlation between gray matter volume (GMV) and white matter hyperintensity (WMH) in ischemic stroke patients using fluid attenuated inversion recovery (FLAIR) sequences. The MRI data were taken randomly from ten ischemic stroke patients (mean age 46.9 years) and ten normal patients (mean age 36.8 years). FLAIR axial image parameters, i.e. TE (time echo), TR (time repetition), and TI (time inversion) were analyzed. The results reveal that the TE and TR values in FLAIR images of normal and ischemic stroke patients are classified as long TE (more than 70 ms), long TR  (more than 1500 ms) and long TI (more than 1700 ms). The mean GMV of ischemic stroke patients (1.371 cm3) is smaller than the GMV of normal patients (2.267 cm3). This is related to the presence of white matter hyperintensity (WMH) in ischemic stroke patients

Associations between dietary patterns and structural neuroimaging markers of relevance for dementia

AbstractBackgroundDiet is a lifestyle factors that could influence the risk of developing dementia. However, the impact of diet on the brain is not fully understood. Investigating associations between dietary patterns and neuroimaging markers of relevance for dementia could potentially increase this understanding.MethodThis study includes cross‐sectional data from the population‐based Gothenburg H70 Birth Cohort Studies, Sweden, including 610 dementia‐free 70‐year‐olds (born 1944, examined 2014‐16) with dietary and magnetic resonance imaging (MRI) data (54% women). Three dietary patterns were derived with principal component analysis, a western‐like pattern (e.g., refined cereal products, sweets, savory bakery/fast food), a Mediterranean‐like pattern (e.g., vegetables, fruits, whole grain cereal products) and a low‐fiber and high‐alcohol pattern (e.g., red meat/processed red meat, eggs, alcoholic beverages). Brain MRI markers were of overall neurodegeneration (i.e., mean cortical thickness), Alzheimer’s disease (AD) neurodegeneration (based on cortical thickness of AD‐signature areas), and vascular brain pathology including early abnormalities in the white matter microstructure (derived from diffusion tensor imaging) and small vessel disease (presence of white matter hyperintensities, lacunes, cerebral microbleeds, and/or perivascular spaces). In data analysis, linear and ordinal regression models were adjusted for sex, energy intake, educational level, physical activity level, smoking and body mass index.ResultResults from this study showed a positive association between higher adherence to the Mediterranean‐like dietary pattern and higher white matter microstructural integrity (B 0.077; 95% CI 0.002 – 0.153). Moreover, a higher adherence to the low‐fibre and high‐alcohol dietary pattern was negatively associated with total mean cortical thickness (B ‐0.011; 95% CI ‐0.019 – ‐0.003) and an AD signature of cortical thickness (mean entorhinal, inferior temporal, middle temporal, and fusiform thickness) (B ‐0.013; 95% CI ‐0.024 – ‐0.001) in the fully adjusted models. No associations were found between the dietary patterns and the small vessel disease markers. Nor were there any associations between the western‐like dietary pattern and the MRI markers.ConclusionThis study suggests that there may be an association between certain dietary patterns and dementia‐related alterations. These findings could be of importance for dementia prevention strategies and for future intervention studies investigating the effect of dietary patterns in relation to dementia.

Late-life depressive symptoms and white matter structural integrity within older Black adults.

Older Black adults experience a high burden of depressive symptoms and cerebrovascular disease but the specific neurobiological substrates underlying the association between late-life depressive symptoms and brain integrity are understudied, particularly in within-group designs. Using the Center for Epidemiologic Studies Depression Scale and diffusion-tensor imaging, within-Black variation in the association between late-life depressive symptoms and white matter structural integrity was examined in 297 older Black participants without dementia that were enrolled across three epidemiological studies of aging and dementia. Linear regression models were used to test associations with DTI metrics (fractional anisotropy, trace of the diffusion tensor) as the outcomes and depressive symptoms as the predictor, while adjusting for age, sex, education, scanner, serotonin-reuptake inhibitor use, total volume of white-matter hyperintensities normalized by intracranial volume, and presence of white-matter hyperintensities at the voxel level. Higher level of self-reported late-life depressive symptoms was associated with greater diffusion-tensor trace (reduced white matter integrity) in connections between commissural pathways and contralateral prefrontal regions (superior and middle frontal/dorsolateral prefrontal cortex), association pathways connecting dorsolateral prefrontal cortex with insular, striatal and thalamic regions, and association pathways connecting the parietal, temporal and occipital lobes and the thalamus. This study demonstrated a discernable pattern of compromised white matter structural integrity underlying late-life depressive symptoms within older Black adults.

Weakly supervised perivascular spaces segmentation with salient guidance of Frangi filter.

To develop a weakly supervised 3D perivascular spaces (PVS) segmentation model that combines the filter-based image processing algorithm and the convolutional neural network. We present a weakly supervised learning method for PVS segmentation by combing a rule-based image processing approach Frangi filter with a canonical deep learning algorithm Unet using conditional random field theory. The weighted cross entropy loss function and the training patch selection were implemented for the optimization and to alleviate the class imbalance issue. The performance of the model was evaluated on the Human Connectome Project data. The proposed method increases the true positive rate compared to the rule-based method and reduces the false positive rate by 36% in the weakly supervised training experiment and 39.4% in the supervised training experiment compared to Unet, which results in superior overall performance. In addition, by training the model on manually quality controlled and annotated data which includes the subjects with the presence of white matter hyperintensities, the proposed method differentiates between PVS and white matter hyperintensities, which reduces the false positive rate by 78.5% compared to weakly supervised trained model. Combing the filter-based image processing algorithm and the convolutional neural network algorithm could improve the model's segmentation accuracy, while reducing the training dependence on the large scale annotated PVS mask data by the trained physician. Compared to the filter-based image processing algorithm, the data driven PVS segmentation model using quality-controlled data as the training target could differentiate the white matter hyperintensity from PVS resulting low false positive rate.

Brain iron imaging markers in the presence of white matter hyperintensities

PurposeTo investigate the relationship between pathological brain iron deposition and white matter hyperintensities (WMHs) in cerebral small vessel disease (CSVD), via Monte Carlo simulations of magnetic susceptibility imaging and the development of a novel imaging marker called the Expected Iron Coefficient (EIC). MethodsA synthetic pathological model of a different number of impenetrable spheres at random locations was employed to represent pathological iron deposition. The diffusion process was simulated with a Monte Carlo method with adjustable parameters to manipulate sphere size, distribution, and extracellular properties. Quantitative susceptibility mapping (QSM) was performed in a clinical dataset to study CSVD to derive and evaluate QSM, R2*, the iron microenvironment coefficient (IMC), and the EIC in the presence of WMHs. ResultsThe simulations show that QSM signals increase in the presence of increased tissue iron, confirming that the EIC increases with pathology. Clinical results demonstrate that while QSM, R2*, and the IMC do not show significant differences in brain iron, the EIC does in the context of CSVD. ConclusionThe EIC is more sensitive to subtle changes in brain iron deposition caused by pathology, even when QSM, R2*, and the IMC fail.

Do Mean Platelet Volume and Platelet Distribution Width Have An Association with White Matter Hyperintensities in Migraine Patients?

Abstract Objective: Increased prevalence of white matter hyperintensities (WMH) is reported in migraine patients; however, the pathophysiology and the progression of these lesions are not definitely clear. Mean platelet volume (MPV) and platelet distribution width (PDW) are easily obtained markers for platelet activity. The aim of this study is to evaluate the relationship between the presence of WMH and MPV and PDW in patients with migraine in order to determine the role of platelet activity in the pathophysiology of WMH. Methods: Patients who were admitted to the neurology outpatient clinics of Baskent University Hospital from January 2011 to December 2015 with migraine and between 18 and 55 years of age were evaluated retrospectively. The blood samples were taken and total blood count parameters including MPV and PDW were analyzed. Brain magnetic resonance images were evaluated. Results: Totally, 218 patients were evaluated in this study. Forty-eight (22.0%) patients had WMH in the brain magnetic resonance imaging. In patients with WMH, the median of age was higher than the patients without WMH and the difference was statistically significant (P &lt; 0.05). There was no statistically significant difference between MPV, PDW values, and the presence of WMH. Conclusions: There are multiple theories suggested for the mechanism of WMH, but the major cause and pathophysiology are still undetermined. Our data suggested that increased platelet activity is insufficient by itself to explain the pathophysiology of WMH in migraine patients and to improve the knowledge on this issue further large longitudinal studies should be performed.

Hearing and Ageing.

Age-related hearing loss (ARHL), or presbycusis, occurs in most mammals, humans included, with a different age of onset and magnitude of loss. It is associated with two major symptoms: loss of sensitivity to sound, especially for high pitches, and a reduced ability to understand speech in background noise. This phenomenon involves both the peripheral structures of the inner ear and the central acoustic pathways. Several mechanisms have been identified as pro-ageing in the human cochlea. The main one is the oxidative stress. The inner ear physiological degeneration can be affected by both intrinsic conditions, such as genetic predisposition, and extrinsic ones, such as noise exposure. The magnitude of neuronal loss precedes and exceeds that of inner hair cell loss, which is also less important than the loss of outer hair cells. Patients with HL often develop atrophy of the temporal lobe (auditory cortex) and brain gliosis can contribute to the development of a central hearing loss. The presence of white matter hyperintensities (WMHs) on the MRI, which is radiologic representation of brain gliosis, can justify a central HL due to demyelination in the superior auditory pathways. Recently, the presence of WMHs has been correlated with the inability to correctly understand words in elderly with normal auditory thresholds.

White matter hyperintensity presence, quantity, and location exhibits no association with motor and non-motor manifestations of PD

IntroductionNonspecific areas of brain white matter hyperintensity (WMH) are commonly found in the elderly. Some studies have shown that the presence, quantity, and location of WMHs may be associated with the development of cognitive and motor decline in patients with Parkinson's disease (PD), but the results remain controversial. This study aimed to evaluate the relationship of WMH to motor and non-motor symptoms, including dysautonomia and rapid eye movement sleep behavior disorder (RBD), in patients with PD. MethodsBrain magnetic resonance images were acquired from 120 patients diagnosed with PD and analyzed for WMH classification and quantification. Motor symptoms were quantified using sub-scores of the Movement Disorder Society-Unified Parkinson Disease Rating Scale (MDS-UPDRS)-III. Dysautonomia was evaluated by autonomic reactivity tests, and polysomnography was used for the diagnosis of RBD. ResultsAge, total value of the MDS-UPDRS-III tremor sub-score, and the presence of dysautonomia were found to be linearly positively associated. Specifically, the duration of PD was positively associated with rigidity, bradykinesia, axial symptoms, prevalence of dysautonomia, and RBD sub-scores. However, in the multivariate analysis adjusted for variables of interest, no statistical significance was found for any of the models. ConclusionThe presence, quantity, and location of WMH were not associated with the analyzed motor and non-motor manifestations of PD.

Cerebral Small Vessel Disease and Gait Speed in Older Adults without Dementia

AbstractBackgroundDisturbances in gait have been found to be predictors of dementia and mobility disability in older adults. The relationship between cerebral small vessel disease (CSVD) and gait speed during simple (normal pace walking; NPW) and complex walking (walking‐while talking; WWT) conditions are not well understood. The current study examined the relationship between CSVD (as assessed as white matter hyperintensities and lacunes), NPW and WWT in older adults without dementia.MethodsNPW and WWT speeds were measured in 113 older adults (46.9% female, 53.1%% male, mean age=78.6±6.3) without dementia enrolled in the LonGenity study. Using an established rating system, white matter hyperintensities (WMH) and lacunes of presumed vascular origin were quantified from Fluid Attenuated Inversion Recovery (FLAIR) images from the same participants. Linear regression models adjusted for age, gender, global health, cohort, and estimated total intracranial volume were used to examine the association between NPW and DTW velocity and markers of CSVD.ResultsNumber of WMH in both the basal ganglia and the temporal lobes were associated with slower NPW velocity in our adjusted models (β=‐3.274 cm/s p=.047, β=‐3.113 cm/s p=.048, respectively). Number of frontal lobe WMH was associated with slower NPW velocity in our unadjusted model (β=‐3.316 cm/s p=.017) but not in the adjusted model (β=‐1.521 cm/s p=.262). WMH were not found to be significantly associated with WWT velocity. Lacunes of presumed vascular origin were not found to be significantly associated with neither NPW or DTW velocity. Significant interactions between measures of CSVD and gender, age, or cohort were not found in our models.ConclusionGait is a complex task requiring the integration of both cognitive and motor function across different brain regions. We find here that higher CSVD burden as measured by the presence of WMH in the basal ganglia and temporal lobes are independently associated with slower normal gait velocity. Interestingly, no such association was seen with WWT, a task requiring a higher cognitive load. Further studies are needed to establish temporality of these lesions with declines in gait velocity. Doing so may show utility of CSVD imaging markers as predictors of gait disturbances and dementia.

Gait variability predicts cognitive impairment in older adults with subclinical cerebral small vessel disease.

Advanced methods of gait research, including approaches to quantify variability, and orderliness/regularity/predictability, are increasingly used to identify patients at risk for the development of cognitive impairment. Cerebral small vessel disease (CSVD) is highly prevalent in older adults and is known to contribute to the development of vascular cognitive impairment and dementia (VCID). Studies in preclinical models demonstrate that subclinical alterations precede CSVD-related cognitive impairment in gait coordination. In humans, CSVD also associates with gait abnormalities. The present study was designed to test the hypothesis that increased gait variability and gait asymmetry predict a decline in cognitive performance in older adults with CSVD. To test this hypothesis, we compared cognitive performance and gait function in patients with CSVD (age: 69.8 ± 5.3 years; n = 11) and age- and sex-matched control participants (age: 70.7 ± 5.8 years; n = 11). Based on imaging findings, patients with CSVD were identified [presence of white matter hyperintensities plus silent brain infarcts and/or microhemorrhages on magnetic resonance imaging (MRI) assessment]. Cognitive performance was assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB). Gait parameters were measured during the single and dual tasks, during which participants, in addition to the motor task, completed a series of mental arithmetic calculations. Spatial and temporal parameters of gait variability, symmetry, and permutation entropy were determined using a pressure-sensitive gait mat during single and dual cognitive task conditions. Patients with CSVD exhibited lower performance in a visual learning test (p = 0.030) and in a sustained attention test (p = 0.007). CSVD also affected step time variability (p = 0.009) and step length variability (p = 0.017). Step lengths of CSVD participants were more asymmetric (p = 0.043) than that of controls, while the two groups were statistically similar regarding step time symmetry and entropy of step time and length. Gait variability was inversely associated with sustained attention, especially among CSVD patients, and this relationship was significantly different between the two groups. The association of sustained attention with gait symmetry was also significantly different between the two groups. Our findings provide additional evidence in support of the concept that increased gait variability and asymmetry may predict cognitive impairment in older adults with CSVD.

Cardiac dysfunction in relation to vascular brain injury, cognitive impairment and depressive symptoms; The Heart-Brain Connection Study

Abstract Introduction Cardiovascular disease is an independent contributor to cognitive impairment. With an imminent rise in chronic cardiovascular disease, a better understanding of its effects on brain health is warranted. Impaired blood flow to the brain is one of the main hypothesized mechanisms linking cardiovascular disease with abnormal brain aging. Purpose To investigate relations between (subclinical) cardiac dysfunction and vascular brain injury, cognitive impairment and depressive symptoms, with a side-by-side comparison of cardiac biomarkers and imaging parameters. Methods Multicenter, cross-sectional, observational cohort study among 559 participants: 431 with manifest cardiovascular disease (heart failure [HF], carotid occlusive disease or vascular cognitive impairment) and 128 control participants, all without dementia. Participants underwent 3T heart-brain MRI and cognitive testing. Determinants were cardiac biomarkers (NT-proBNP and high-sensitive Troponin-I) and left ventricular (LV) functional parameters by MRI (LV ejection fraction, cardiac output, LV global function index). Outcome measures were cerebral small vessel disease (CSVD) by MRI (presence of white matter hyperintensities, microbleeds, lacunar infarcts or perivascular spaces), CSVD score (0–4), cognitive impairment in ≥1 domain (memory, language, attention-psychomotor speed and executive functioning) and depressive symptoms (Geriatric Depression Scale-15 score &amp;gt;5). Interaction analyses were used to investigate effect modification by patient group; results are reported pooled or stratified accordingly. Results In patients with cardiovascular disease and controls, but not in those with manifest HF, LV functional parameters were associated with CSVD and cognitive impairment, with the following associations: LVEF &amp;lt;50% with CSVD (OR 4.67 [1.37–15.95]) and CSVD score (RR 1.38 [1.06–1.81]); LV global function index with CSVD (OR 0.71 [0.58–0.86]), CSVD score (RR 0.90 [0.84–0.96]) and cognitive impairment (OR 0.84 [0.72–0.97]). LV global function index (OR 0.82 [0.71–0.95]) and cardiac output (OR 0.81 [0.71–0.93]) were also associated with depressive symptoms in all. These relations were independent from age, sex, hypertension, diabetes, waist-hipratio, history of ischemic heart disease, transient ischemic attack or stroke. Cardiac biomarkers were univariably associated with brain outcome measures, but not in multivariable analysis. Conclusion This study indicates that subclinical cardiac dysfunction, as assessed by cardiovascular MRI, is independently associated with vascular brain injury, cognitive impairment and depressive symptoms. Of all parameters, LV global function index showed the most robust relations, indicating that global cardiac performance is more closely related to poorer brain outcome than merely LV systolic function. In those with clinically manifest HF, the severity of cardiac dysfunction was related to depressive symptoms but not to other brain outcome measures. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The Netherlands CardioVascular Research Initiative; The Dutch Heart Foundation

Triglyceride glucose index is associated with cerebral small vessel disease burden and cognitive impairment in elderly patients with type 2 diabetes mellitus.

ObjectiveTo investigate the relations of Triglyceride glucose (TyG) index with cerebral small vessel disease (CSVD) burden and cognitive function in aged patients with type 2 diabetes mellitus (T2DM).MethodsA total of 308 elderly patients with T2DM were included in this retrospective study. The standardized Chinese version of Mini-Mental State Examination was used to assess cognitive function. The total CSVD burden score was assessed by combining four imaging markers of CSVD, including the presence of white matter hyperintensity, cerebral microbleeds in the deep, lacunes and enlarged perivascular spaces in the basal ganglia. The TyG index was calculated as the formula of ln [fasting triglyceride (mg/dl) × fasting plasma glucose (mg/dl)/2]. We used logistic regression analysis and mediation analysis to investigate the relations of TyG index with CSVD and cognitive function.ResultsMultivariate binary logistic regression analysis showed that increased TyG index (OR: 2.241; 95% Confidence Interval(CI): 1.439 to 3.490; P <0.001), or severe CSVD burden (OR: 2.198; 95% CI: 1.283 to 3.763; P = 0.004) was associated with an increased risk of cognitive impairment in elderly patients with T2DM after adjusting for potential confounders. In addition, TyG index was an independent risk factor of severe CSVD burden (OR: 1.472; 95% CI: 1.003 to 2.160; P = 0.048) after controlling for potential confounders. Compared with the lowest TyG index tertile, the multivariable-adjusted OR of the highest tertile was 3.298 (95% CI: 1.685 to 6.452; P for trend <0.001) for cognitive impairment, 1.933 (95% CI: 1.010 to 3.698; P for trend = 0.047) for severe CSVD burden. Mediation analysis found a significant moderating effect of the severe CSVD burden on the association between higher TyG index levels and cognitive impairment.ConclusionsThe increased TyG index is an independent risk factor for cognitive impairment and severe CSVD burden in clinical practice. A proportion of the effect of increased TyG index on cognitive impairment may be due to the aggravation of CSVD burden.

Cerebral small vessel disease as imaging biomarker predicting ocular cranial nerve palsy of presumed ischemic origin at admission

Ocular cranial nerve palsy of presumed ischemic origin (OCNPi) is the most common type of ocular cranial nerve palsy (OCNP) in patients aged ≥ 50 years; however, no definite diagnostic test exists. As diagnostic criteria include clinical improvement, diagnoses are often delayed. Diagnostic biomarkers for OCNPi are required; we hypothesized that cerebral small vessel disease is associated with OCNPi. We analyzed 646 consecutive patients aged ≥ 50 years with isolated unilateral OCNP who underwent work-ups at two referral hospitals. White matter hyperintensities (WMHs), silent infarctions, and cerebral microbleeds (CMBs) were assessed. In multivariate analyses, mild (grades 1–3) and moderate to severe (grades 4–6) WMHs were significantly associated with OCNPi compared to OCNP of other origins (odds ratio [OR] 3.51, 95% confidence interval [CI] 1.91–6.43, P < 0.001; OR 3.47, 95% CI 1.42–8.48, P = 0.006, respectively). Silent infarction and CMBs did not remain associated (OR 0.96, 95% CI 0.54–1.70, P = 0.870; OR 0.55, 95% CI 0.28–1.08, P = 0.080, respectively). Associations between WMH and OCNPi remained after excluding patients with vascular risk factors. In conclusion, the presence of WMH could independently predict ischemic origin in patients with isolated unilateral OCNP at early stage of admission.