Total White Matter Hyperintensities Research Articles

Subtle signs of atrial cardiomyopathy and left ventricular diastolic dysfunction are associated with reduced cognitive function: results from the Hamburg City Health Study.

Atrial fibrillation is associated with cognitive dysfunction. Atrial cardiomyopathy has been correlated with both entities. We aimed to characterize the association of echocardiographic parameters of atrial cardiomyopathy with cognitive function and cerebral changes. Participants of the population-based Hamburg City Health Study underwent in-depth transthoracic echocardiography and cognitive function testing, the Animal Naming Test (ANT), the Trail Making Test A (TMT-A) and B (TMT-B), 10-word learning test and cerebral magnetic resonance imaging. After excluding individuals with stroke or depression, data from 7852 individuals were available. In multi-variable-adjusted regression analyses, the E/e'-ratio was associated with the level of impairment in the ANT (-0.19 per one standard deviation [SD] increase, 95% confidence interval [CI] -0.36-[-0.01]) and the TMT-A (0.01 per one SD increase, 95% CI 0.003-0.020). Left atrial global peak strain was associated with positive performance in the TMT-A and B (-0.01 per one SD increase [95% CI -0.02-(-0.002)] and -0.02 per one SD increase [95% CI -0.03-(-0.01)], respectively) and the immediate recall of the 10-word learning test (0.11 per one SD increase, 95% CI 0.02-0.20). The E/e'-ratio was positively associated with the total and periventricular white matter hyperintensity load in age- and sex-adjusted regression analyses though statistical significance was lost after multi-variable adjustment. Subclinical echocardiographic signs of atrial cardiomyopathy and left ventricular diastolic dysfunction are associated with impaired performance in cognitive tests in the population. Our data provide evidence of the clinically important cardio-cerebral axis, relating cardiac dysfunction with cognitive performance.

Traumatic brain injury, posttraumatic stress disorder, and vascular risk are independently associated with white matter aging in Vietnam-Era veterans.

Traumatic brain injury (TBI), mental health conditions (e.g., posttraumatic stress disorder [PTSD]), and vascular comorbidities (e.g., hypertension, diabetes) are highly prevalent in the Veteran population and may exacerbate age-related changes to cerebral white matter (WM). Our study examined (1) relationships between health conditions-TBI history, PTSD, and vascular risk-and cerebral WM micro- and macrostructure, and (2) associations between WM measures and cognition. We analyzed diffusion tensor images from 183 older male Veterans (mean age = 69.18; SD = 3.61) with (n = 95) and without (n = 88) a history of TBI using tractography. Generalized linear models examined associations between health conditions and diffusion metrics. Total WM hyperintensity (WMH) volume was calculated from fluid-attenuated inversion recovery images. Robust regression examined associations between health conditions and WMH volume. Finally, elastic net regularized regression examined associations between WM measures and cognitive performance. Veterans with and without TBI did not differ in severity of PTSD or vascular risk (p's >0.05). TBI history, PTSD, and vascular risk were independently associated with poorer WM microstructural organization (p's <0.5, corrected), however the effects of vascular risk were more numerous and widespread. Vascular risk was positively associated with WMH volume (p = 0.004, β=0.200, R2 = 0.034). Higher WMH volume predicted poorer processing speed (R2 = 0.052). Relative to TBI history and PTSD, vascular risk may be more robustly associated with WM micro- and macrostructure. Furthermore, greater WMH burden is associated with poorer processing speed. Our study supports the importance of vascular health interventions in mitigating negative brain aging outcomes in Veterans.

White Matter Hyperintensities and Cognitive Functions in People With the R544C Variant of the NOTCH3 Gene Without Stroke or Dementia.

NOTCH3 pathologic variants cause cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), which presents with stroke and dementia and is characterized by white matter hyperintensities (WMHs) on brain MRI. The R544C variant is a common pathologic variant in Taiwan, but not all carriers exhibit significant symptoms. We investigated whether WMHs occur before clinical symptoms in carriers with pathogenic variants, examined factors associated with WMHs, and explored their relationship with cognitive functions. We enrolled 63 R544C carriers without overt clinical disease (WOCD) and 37 age-matched and sex-matched noncarriers as controls from the Taiwan Precision Medicine Initiative data set. All participants underwent clinical interviews, comprehensive neuropsychological assessments, and brain MRI. We calculated total and regional WMH volumes, determined the age at which WMHs began increasing in carriers, and examined the relationship between WMHs and neuropsychological performance. Factors associated with WMH volumes were analyzed using multivariable linear regression models. Compared with controls, R544C carriers WOCD had increased WMH volume, except in the occipital and midbrain areas, and showed a rapid increase in WMHs starting at age 48. They scored lower on the Mini-Mental State Examination (median = 28.4 vs 29.0, p = 0.048), Montreal Cognitive Assessment (MoCA) (median = 28.3 vs 29.0, p = 0.013), and memory and executive function tests than controls. After adjusting for age, sex, and education, MoCA scores were associated with whole-brain (r = -0.387, padj = 0.008) and regional WMHs (all padj < 0.05) except in the midbrain area. Age (β = 0.034, 95% CI 0.021-0.046, p < 0.001), hypercholesterolemia (β = 0.375, 95% CI 0.097-0.653, p = 0.009), and the vascular risk factor (VRF) index (β = 0.132, 95% CI 0.032-0.242, p = 0.019) were associated with the WMH severity in carriers. Our study revealed that WMHs are extensively distributed in R544C carriers WOCD. They exhibited a rapid increase in WMHs beginning at age 48, approximately 7 years earlier than the reported age at symptomatic onset. Age was the strongest predictive factor of WMHs, and VRF, particularly hypercholesterolemia, might be modifying factors of WMHs.

Large sample size MRI measurements to assess the relation between cardiac function and structure and white matter hyperintensity volumes

Abstract Background People with established cardiovascular disease (CVD) are at risk of early cognitive decline, and neurological diseases such as dementia. CVD and neurological diseases share common risk factors, such as blood pressure, sedentary lifestyle, as well as genomic risk factors such as mutations in APOE4 [1]. It's unclear to what extent the co-occurrence of CVD and neurological diseases is explained by these risk factors, or whether there is a direct association where CVD is a first step towards poorer neurological health. White matter hyperintensities (WMH) of presumed vascular origin are damaged areas in the brain observed through magnetic resonance imaging (MRI). These lesions are associated with progressive neurological disease such as vascular dementia, as well with risk factors for CVD [2]. Purpose We set out to determine to what extent CMR measurements associated with WMH independent of known cerebrovascular risk factors. Methods Cardiac and brain MRI images were analysed for 23,963 UK biobank (UKB) participants. WMH analysis included 5 brain regions (Frontal[F], Parietal[P], Temporal[T], Occipital[O], Basal Ganglia and Thalami [BGT]) and total brain WMH volume. Cardiac traits included stroke volumes, atrial volumes, ejection fractions of right and left chambers, left ventricular (LV) strain, LV wall thickness and aortic areas. Multivariable regression analysis was carried out, where each cardiac trait was regressed on each brain region and adjusted for: age, difference between age at initial visit and imaging visit, sex, systolic and diastolic blood pressure, Hba1c, household income, educational status, Townsend score and family history of disease (Alzheimer’s, Parkinson's, high blood pressure, stroke, heart disease) . Results were evaluated against a multiple testing correct p-value threshold of 0.05, reflecting the number of principle components(n=10) necessary to explain 90% of the cardiac trait variability. Results For 5 cardiac traits (right ventricular stroke volume, left atrial stroke volume, left ventricular stroke volume, left ventricular ejection fraction and right ventricular end diastolic volume) higher values were associated with lower WMH volumes in all brain regions. Additionally, some cardiac traits such as LV cardiac output associated with specific brain regions (T, O, BGT). Additionally, APOE- ε4 stratified analyses indicated, homozygous carriers show a greater association between higher minimum LA and RA volumes and higher WMH volumes in the occipital lobe. Conclusions This study gives an insight into the WMH burden in a large population of adults. It highlights the associations of cardiac traits with white matter hyperintensity volumes in different brain regions independent of known risk factors. Using cardiac traits as surrogate markers of different cardiac disease could explain how cardiac functionality defines WMH volume distribution and subsequently the wider relationship between CVD and cerebrovascular disease.Figure 1Graphical Abstract

Choroid Plexus Volume in Rural Chinese Older Adults: Distribution and Association With Cardiovascular Risk Factors and Cerebral Small Vessel Disease.

The choroid plexus (CP) is involved in neurodegenerative diseases. However, the association of CP with cardiovascular risk factors and cerebral small vessel disease in older adults remains unclear. This population-based study included 1263 participants (60 years and older) from the MIND-China (Multimodal Interventions to Delay Dementia and Disability in Rural China) substudy (2018-2020), of which 111 individuals completed diffusion tensor imaging examination. CP volume was automatically segmented. White matter hyperintensities (WMHs), enlarged perivascular spaces (EPVS), cerebral microbleeds, and lacunes were assessed following the Standards for Reporting Vascular Changes on Neuroimaging 1. Peak width of skeletonized mean diffusivity and free water were derived from diffusion tensor imaging images. We used linear regression models to evaluate the association between CP volume and cardiovascular risk factors, WMH volumes, and diffusion tensor imaging metrics, and logistic regression models to examine the association between CP volume and EPVS, cerebral microbleeds, and lacunes. The CP volume increased with age (P<0.001). Men (β coefficient=0.47 [95% CI, 0.29-0.64]) and participants with diabetes (β coefficient=0.16 [95% CI, 0.01-0.31]) had larger CP volumes than women and individuals without diabetes, respectively (P<0.05). Greater CP volume was significantly associated with larger total and periventricular WMH volumes and moderate to severe EPVS in basal ganglia (P<0.05) but not with deep WMHs, EPVS in centrum semiovale, lacunes, or cerebral microbleeds. In the diffusion tensor imaging subsample, enlarged CP was significantly associated with higher peak width of skeletonized mean diffusivity and free water of periventricular and deep white matter (P<0.05). An enlarged CP is associated with larger global and periventricular WMH volume and higher likelihoods of EPVS in basal ganglia and impaired white matter integrity, suggesting that an enlarged CP may represent a precursor of cerebral small vessel disease.

Association between Life’s Essential 8 and Cerebral Small Vessel Disease

BackgroundGiven that associations of Life’s Essential 8 (LE8) and cerebral small vessel disease (CSVD) or its imaging markers were unclear, we examined relationship between them.MethodsThe cross-sectional study included community residents...

Magnitude and kinetics of a set of neuroanatomic volume and thickness together with white matter hyperintensity is definitive of cognitive status and brain age

Even among the subjects classified as cognitively normal, there exists a subset of individuals at a given chronological age (CA) who harbor white matter hyperintensity (WMH) while another subset presents with low or undetectable WMH. Here, we conducted a comprehensive MRI segmentation of neuroanatomic structures along with WMH quantification in groups of cognitively normal (CN), cognitively impaired (CI) individuals, and individuals with an etiological diagnosis of cognitive impairment owing to Alzheimer’s Disease (CI-AD) across the early (50–64 years), intermediate (65–79 years), and late (≥80 years) age groups from the NACC cohort. Neuroanatomic volumetry quantification revealed that thinning of the parahippocampal gyrus in the early (p = 0.016) and intermediate age groups (p = 0.0001) along with an increase in CSF (p = 0.0009) delineates between CI and CI-AD subjects. Although, a significant loss of ~5–10% in volume of gray matter (p(CN vs CI) < 0.0001, p(CN vs CI-AD) < 0.0001), white matter (p(CN vs CI) = 0.002, p(CN vs CI-AD) = 0.0003) and hippocampus (p(CN vs CI) = 0.007, p(CN vs CI-AD) < 0.0001) was evident at the early age groups in the CI and CI-AD compared to CN but it was not distinct between CI and CI-AD. Using the neuroanatomic and WMH volume, and the supervised decision tree-based ML modeling, we have established that a minimum set of Three brain quantities; Total brain (GM + WM), CSF, and WMH volume, provide the Optimal quantitative features discriminative of cognitive status as CN, CI, and CI-AD. Furthermore, using the volume/thickness of 178 neuroanatomic structures, periventricular and deep WMH volume quantification for the 819 CN subjects, we have developed a quantitative index as ‘Brain Age’ (BA) depictive of neuroanatomic health at a given CA. Subjects with elevated WMH load (5–10 ml) had increased BA ( + 0.6 to +4 years) than the CA. Increased BA in the subjects with elevated WMH is suggestive of WMH-induced vascular insult leading to accelerated and early structural loss than expected for a given CA. Henceforth, this study establishes that quantification of WMH together with an optimal number of neuroanatomic features is mandatory to delve into the biological underpinning of aging and aging-associated cognitive disorders.

White matter variations in congenital adrenal hyperplasia: possible implications for glucocorticoid treatment.

Congenital adrenal hyperplasia has been reported to manifest with white matter aberrations. However, many previous studies included only small samples, restricted their analyses to females, lacked a control group and/or did not correct for brain size. Here, we examined the largest sample to date, comprising 53 male and female participants with congenital adrenal hyperplasia, who were matched with 53 male and female controls in terms of sex, age, education, and verbal intelligence. The four groups were compared with respect to their total white matter as well as white matter hyperintensities while applying brain size corrections. For both measures, total white matter and white matter hyperintensities, there were no significant sex differences or group-by-sex interactions. However, individuals with congenital adrenal hyperplasia had significantly smaller total white matter volumes compared to controls. Our findings align with previous reports of white matter variations in congenital adrenal hyperplasia. The absence of a group-by-sex interaction suggests that white matter variations in congenital adrenal hyperplasia may not be attributable to prenatal androgens. Instead, they may be a result of the condition itself and/or its treatment with glucocorticoids. The latter aspect warrants follow-up, particularly given that glucocorticoids are employed not only in congenital adrenal hyperplasia but also in other medical conditions.

The Different Associations of White Matter Hyperintensities With Severity of Dementia and Cognitive Impairment According to the Distance From the Lateral Ventricular Surface in Patients With Alzheimer's Disease.

White matter hyperintensities (WMH) are common among the elderly. Although WMH play a key role in lowering the threshold for the clinical expression of dementia in Alzheimer's disease (AD)-related pathology, the clinical significance of their location is not fully understood. This study aimed to investigate the association between WMH and cognitive function according to the location of WMH in AD. Subjects underwent clinical evaluations including volumetric brain magnetic resonance imaging study and neuropsychological tests using the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease Assessment Packet. WMH were calculated using automated quantification method. According to the distance from the lateral ventricular surface, WMH within 3 mm, WMH within 3-13 mm, and WMH over 13 mm were classified as juxtaventricular WMH (JVWMH), periventricular WMH (PVWMH), and deep WMH (DWMH), respectively. Total WMH volume was associated with poor performance in categorical verbal fluency test (β=-0.197, p=0.035). JVWMH volume was associated with poor performances on categorical verbal fluency test (β=-0.201, p=0.032) and forward digit span test (β= -0.250, p=0.012). PVWMH volume was associated with poor performances on categorical verbal fluency test (β=-0.185, p=0.042) and word list memory test (β=-0.165, p=0.042), whereas DWMH volume showed no association with cognitive tests. PVWMH volume were also related to Clinical Dementia Rating Scale Sum of Boxes score (β=0.180, p=0.026). WMH appear to exhibit different associations with the severity of dementia and cognitive impairment according to the distance from ventricle surface in AD.

The relationship between intracranial atherosclerosis and white matter hyperintensity in ischemic stroke patients: a retrospective cross-sectional study using high-resolution magnetic resonance vessel wall imaging.

Both intracranial atherosclerosis and white matter hyperintensity (WMH) are prevalent among the stroke population. However, the relationship between intracranial atherosclerosis and WMH has not been fully elucidated. Therefore, the aim of this study was to investigate the relationship between the characteristics of intracranial atherosclerotic plaques and the severity of WMH in patients with ischemic stroke using high-resolution magnetic resonance vessel wall imaging. Patients hospitalized with ischemic stroke and concurrent intracranial atherosclerosis at Beijing Tsinghua Changgung Hospital, a tertiary comprehensive stroke center, who underwent high-resolution magnetic resonance vessel wall imaging and conventional brain magnetic resonance imaging were continuously recruited from January 2018 to December 2018. Both intracranial plaque characteristics (plaque number, maximum wall thickness, luminal stenosis, T1 hyperintensity, and plaque length) and WMH severity (Fazekas score and volume) were evaluated. Spearman correlation or point-biserial correlation analysis was used to determine the association between clinical characteristics and WMH volume. The independent association between intracranial plaque characteristics and the severity as well as WMH score was analyzed using logistic regression. The associations of intracranial plaque characteristics with total white matter hyperintensity (TWMH) volume, periventricular white matter hyperintensity (PWMH) volume and deep white matter hyperintensity (DWMH) volume were determined using multilevel mixed-effects linear regression. A total of 159 subjects (mean age: 64.0±12.5 years; 103 males) were included into analysis. Spearman correlation analysis indicated that age was associated with TWMH volume (r=0.529, P<0.001), PWMH volume (r=0.523, P<0.001) and DWMH volume (r=0.515, P<0.001). Point-biserial correlation analysis indicated that smoking (r=-0.183, P=0.021) and hypertension (r=0.159, P=0.045) were associated with DWMH volume. After adjusting for confounding factors, logistic regression analysis showed plaque number was significantly associated with the presence of severe WMH [odds ratio (OR), 1.590; 95% CI, 1.241-2.035, P<0.001], PWMH score of 3 (OR, 1.726; 95% CI, 1.074-2.775, P=0.024), and DWMH score of 2 (OR, 1.561; 95% CI, 1.150-2.118, P=0.004). Intracranial artery luminal stenosis was associated with presence of severe WMH (OR, 1.032; 95% CI, 1.002-1.064, P=0.039) and PWMH score of 2 (OR, 1.057; 95% CI, 1.008-1.109, P=0.023). Multilevel mixed-effects linear regression analysis showed that plaque number was associated with DWMH volume (β=0.128; 95% CI, 0.016-0.240; P=0.026) after adjusted for age and sex. In ischemic stroke patients, intracranial atherosclerotic plaque characteristics as measured by plaque number and luminal stenosis were associated with WMH burden.

Characterization of white matter hyperintensities in Down syndrome.

In Down syndrome (DS), white matter hyperintensities (WMHs) are highly prevalent, yet their topography and association with sociodemographic data and Alzheimer's disease (AD) biomarkers remain largely unexplored. In 261 DS adults and 131 euploid controls, fluid-attenuated inversion recovery magnetic resonance imaging scans were segmented and WMHs were extracted in concentric white matter layers and lobar regions. We tested associations with AD clinical stages, sociodemographic data, cerebrospinal fluid (CSF) AD biomarkers, and gray matter (GM) volume. In DS, total WMHs arose at age 43 and showed stronger associations with age than in controls. WMH volume increased along the AD continuum, particularly in periventricular regions, and frontal, parietal, and occipital lobes. Associations were found with CSF biomarkers and temporo-parietal GM volumes. WMHs increase 10 years before AD symptom onset in DS and are closely linked with AD biomarkers and neurodegeneration. This suggests a direct connection to AD pathophysiology, independent of vascular risks. White matter hyperintensities (WMHs) increased 10 years before Alzheimer's disease symptom onset in Down syndrome (DS). WMHs were strongly associated in DS with the neurofilament light chain biomarker. WMHs were more associated in DS with gray matter volume in parieto-temporal areas.

High cognitive reserve attenuates the risk of dementia associated with cardiometabolic diseases

BackgroundCardiometabolic diseases (CMDs) including type 2 diabetes, heart disease, and stroke have been linked to a higher risk of dementia. We examined whether high levels of cognitive reserve (CR) can attenuate the increased dementia risk and brain pathologies associated with CMDs.MethodsWithin the UK Biobank, 216,178 dementia-free participants aged ≥ 60 were followed for up to 15 years. Baseline CMDs and incident dementia were ascertained from medical records, medication use, and medical history. Latent class analysis was used to generate an indicator of CR (low, moderate, and high) based on education, occupational attainment, confiding in others, social contact, leisure activities, and television watching time. A subsample (n = 13,663) underwent brain MRI scans during follow-up. Volumes of total gray matter (GMV), hippocampus (HV), and white matter hyperintensities (WMHV) were ascertained, as well as mean diffusivity (MD) and fractional anisotropy (FA) in white matter tracts.ResultsAt baseline, 43,402 (20.1%) participants had at least one CMD. Over a mean follow-up of 11.7 years, 6,600 (3.1%) developed dementia. The presence of CMDs was associated with 57% increased risk of dementia (HR 1.57 [95% CI 1.48, 1.67]). In joint effect analysis, the HRs of dementia for people with CMDs and moderate-to-high CR and low CR were 1.78 [1.66, 1.91] and 2.13 [1.97, 2.30]), respectively (reference: CMD-free, moderate-to-high CR). Dementia risk was 17% lower (HR 0.83 [0.77, 0.91], p < 0.001) among people with CMDs and moderate-to-high compared to low CR. On brain MRI, CMDs were associated with smaller GMV (β -0.18 [-0.22, -0.13]) and HV (β -0.13 [-0.18, -0.08]) as well as significantly larger WMHV (β 0.06 [0.02, 0.11]) and MD (β 0.08 [0.02, 0.13]). People with CMDs and moderate-to-high compared to low CR had significantly larger GMV and HV, but no differences in WMHV, MD, or FA.ConclusionsAmong people with CMDs, having a higher level of CR was associated with lower dementia risk and larger gray matter and hippocampal volumes. The results highlight a mentally and socially active life as a modifiable factor that may support cognitive and brain health among people with CMDs.

Brain structure, amyloid, and behavioral features for predicting clinical progression in subjective cognitive decline.

As a potential preclinical stage of Alzheimer's dementia, subjective cognitive decline (SCD) reveals a higher risk of future cognitive decline and conversion to dementia. However, it has not been clear whether SCD status increases the clinical progression of older adults in the context of amyloid deposition, cerebrovascular disease (CeVD), and psychiatric symptoms. We identified 99 normal controls (NC), 15 SCD individuals who developed mild cognitive impairment in the next 2 years (P-SCD), and 54 SCD individuals who did not (S-SCD) from ADNI database with both baseline and 2-year follow-up data. Total white matter hyperintensity (WMH), WMH in deep (DWMH) and periventricular (PWMH) regions, and voxel-wise grey matter volumes were compared among groups. Furthermore, using structural equation modelling method, we constructed path models to explore SCD-related brain changes longitudinally and to determine whether baseline SCD status, age, and depressive symptoms affect participants' clinical outcomes. Both SCD groups showed higher baseline amyloid PET SUVR, baseline PWMH volumes, and larger increase of PWMH volumes over time than NC. In contrast, only P-SCD had higher baseline DWMH volumes and larger increase of DWMH volumes over time than NC. No longitudinal differences in grey matter volume and amyloid was observed among NC, S-SCD, and P-SCD. Our path models demonstrated that SCD status contributed to future WMH progression. Further, baseline SCD status increases the risk of future cognitive decline, mediated by PWMH; baseline depressive symptoms directly contribute to clinical outcomes. In conclusion, both S-SCD and P-SCD exhibited more severe CeVD than NC. The CeVD burden increase was more pronounced in P-SCD. In contrast with the direct association of depressive symptoms with dementia severity progression, the effects of SCD status on future cognitive decline may manifest via CeVD pathologies. Our work highlights the importance of multi-modal longitudinal designs in understanding the SCD trajectory heterogeneity, paving the way for stratification and early intervention in the preclinical stage. PRACTITIONER POINTS: Both S-SCD and P-SCD exhibited more severe CeVD at baseline and a larger increase of CeVD burden compared to NC, while the burden was more pronounced in P-SCD. Baseline SCD status increases the risk of future PWMH and DWMH volume accumulation, mediated by baseline PWMH and DWMH volumes, respectively. Baseline SCD status increases the risk of future cognitive decline, mediated by baseline PWMH, while baseline depression status directly contributes to clinical outcome.

Prolonged ventricular repolarization associated with mild cognitive impairment and white matter hyperintensities: a cross-sectional study

Prolonged ventricular repolarization has been associated with cardiovascular disease. We sought to investigate the association of prolonged ventricular repolarization with mild cognitive impairment (MCI) and the potential underlying neuropathological mechanisms in older adults. This cross-sectional study included 4328 dementia-free participants (age ≥ 65 years; 56.8% female) in the baseline examination of the Multidomain INterventions to delay dementia and Disability in rural China; of these, 989 undertook structural brain magnetic resonance imaging (MRI) scans. QT, QTc, JT, JTc, and QRS intervals were derived from 12-lead electrocardiograph. MCI, amnestic MCI (aMCI), and non-amnestic MCI (naMCI) were defined following the Petersen’s criteria. Volumes of gray matter (GM), white matter, cerebrospinal fluid, total white matter hyperintensities (WMH), periventricular WMH (PWMH), and deep WMH (DWMH) were automatically estimated. Data were analyzed using logistic and general linear regression models. Prolonged QT, QTc, JT, and JTc intervals were significantly associated with an increased likelihood of MCI and aMCI, but not naMCI (p < 0.05). In the MRI subsample, QT, QTc, JT, and JTc intervals were significantly associated with larger total WMH and PWMH volumes (p < 0.05), but not with DWMH volume. Statistical interactions were detected, such that prolonged QT and JT intervals were significantly associated with reduced GM volume only among participants with coronary heart disease or without APOE ε4 allele (p < 0.05). Prolonged ventricular repolarization is associated with MCI and cerebral microvascular lesions in a general population of older adults. This underlies the importance of cognitive assessments and brain MRI examination among older adults with prolonged QT interval.

Strategic white matter hyperintensity locations associated with post-stroke cognitive impairment: A multicenter study in 1568 stroke patients.

Post-stroke cognitive impairment (PSCI) occurs in up to 50% of stroke survivors. Presence of pre-existing vascular brain injury, in particular the extent of white matter hyperintensities (WMH), is associated with worse cognitive outcome after stroke, but the role of WMH location in this association is unclear. We determined if WMH in strategic white matter tracts explain cognitive performance after stroke. Individual patient data from nine ischemic stroke cohorts with magnetic resonance imaging (MRI) were harmonized through the Meta VCI Map consortium. The association between WMH volumes in strategic tracts and domain-specific cognitive functioning (attention and executive functioning, information processing speed, language and verbal memory) was assessed using linear mixed models and lasso regression. We used a hypothesis-driven design, primarily addressing four white matter tracts known to be strategic in memory clinic patients: the left and right anterior thalamic radiation, forceps major, and left inferior fronto-occipital fasciculus. The total study sample consisted of 1568 patients (39.9% female, mean age = 67.3 years). Total WMH volume was strongly related to cognitive performance on all four cognitive domains. WMH volume in the left anterior thalamic radiation was significantly associated with cognitive performance on attention and executive functioning and information processing speed and WMH volume in the forceps major with information processing speed. The multivariable lasso regression showed that these associations were independent of age, sex, education, and total infarct volume and had larger coefficients than total WMH volume. These results show tract-specific relations between WMH volume and cognitive performance after ischemic stroke, independent of total WMH volume. This implies that the concept of strategic lesions in PSCI extends beyond acute infarcts and also involves pre-existing WMH. The Meta VCI Map consortium is dedicated to data sharing, following our guidelines.

Cerebral white matter hyperintensities in adults born small for gestational age at 12 years after cessation of childhood growth hormone treatment: a prospective cohort study including untreated controls

Increased cerebrovascular morbidity was reported in adults born small for gestational age (SGA) who were treated with growth hormone (GH) during childhood compared to the general population. Yet, previous studies lacked an appropriate control group which is a major limitation. We prospectively studied cerebral white matter hyperintensities (WMHs) in adults born SGA at 12 years after cessation of childhood GH-treatment (SGA-GH), compared to appropriate controls. In this prospective cohort study, performed between May 2016 and December 2020, total WMHs, periventricular WMHs (PVWMHs) and deep WMHs (DWMHs) were the primary outcomes of the study, they were qualitatively assessed using 3Tesla (T) Magnetic Resonance Imaging (MRI) and scored using the Fazekas scale in SGA-GH adults and in 3 untreated control groups: adults born SGA with persistent short stature (SGA-S), adults born SGA with spontaneous catch-up growth to a normal height (SGA-CU) and adults born appropriate for gestational age with a normal height (AGA). Regression analyses were performed in the total cohort to evaluate the associations of GH-treatment and birth characteristics with WMHs. 297 adults were investigated (91 SGA-GH, 206 controls). Prevalence of total WMHs was 53.8% (95% CI 43.1-64.3) in SGA-GH, 40.5% (95% CI 25.6-56.7) in SGA-S, 73.9% (95% CI 61.9-83.7) in SGA-CU and 41.1% (95% CI 31.1-51.6) in AGA adults. No statistically significant differences in total WMHs, PVWMHs and DWMHs were found between SGA-GH compared to SGA-S and AGA adults. Highest prevalence of all type of WMHs was found in SGA-CU adults compared to all groups. Higher prevalence of total WMHs was associated with lower birth weight standard deviation score (SDS), but not with GH-treatment. Our findings suggest that GH-treatment in children born SGA has no negative impact on the prevalence of all type of WMHs at 12 years after GH cessation compared to appropriate controls. SGA-CU adults had the highest prevalence of all type of WMHs around age 30 years. Novo Nordisk.

The Associations Between Serum Insulin-like Growth Factor-I, Brain White Matter Volumes, and Cognition in Mild Cognitive Impairment and Alzheimer's Disease.

Insulin-like growth factor-I (IGF-I) regulates myelin, but little is known whether IGF-I associates with white matter functions in subjective and objective mild cognitive impairment (SCI/MCI) or Alzheimer's disease (AD). To explore whether serum IGF-I is associated with magnetic resonance imaging - estimated brain white matter volumes or cognitive functions. In a prospective study of SCI/MCI (n = 106) and AD (n = 59), we evaluated the volumes of the total white matter, corpus callosum (CC), and white matter hyperintensities (WMHs) as well as Mini-Mental State Examination (MMSE), Trail Making Test A and B (TMT-A/B), and Stroop tests I-III at baseline, and after 2 years. IGF-I was comparable in SCI/MCI and AD (113 versus 118 ng/mL, p = 0.44). In SCI/MCI patients, the correlations between higher baseline IGF-I and greater baseline and 2-year volumes of the total white matter and total CC lost statistical significance after adjustment for intracranial volume and other covariates. However, after adjustment for covariates, higher baseline IGF-I correlated with better baseline scores of MMSE and Stroop test II in SCI/MCI and with better baseline results of TMT-B and Stroop test I in AD. IGF-I did not correlate with WMH volumes or changes in any of the variables. Both in SCI/MCI and AD, higher IGF-I was associated with better attention/executive functions at baseline after adjustment for covariates. Furthermore, the baseline associations between IGF-I and neuropsychological test results in AD may argue against significant IGF-I resistance in the AD brain.

Cardiovascular disease risk exacerbates brain aging among Hispanic/Latino adults in the SOL-INCA-MRI Study.

Cardiovascular disease (CVD) risk factors are highly prevalent among Hispanic/Latino adults, while the prevalence of MRI infarcts is not well-documented. We, therefore, sought to examine the relationships between CVD risk factors and infarcts with brain structure among Hispanic/Latino individuals. Participants included 1,886 Hispanic/Latino adults (50-85 years) who underwent magnetic resonance imaging (MRI) as part of the Study of Latinos-Investigation of Neurocognitive Aging-MRI (SOL-INCA-MRI) study. CVD risk was measured approximately 10.5 years before MRI using the Framingham cardiovascular risk score, a measure of 10-year CVD risk (low (<10%), medium (10- < 20%), and high (≥20%)). MR infarcts were determined as present or absent. Outcomes included total brain, cerebral and lobar cortical gray matter, hippocampal, lateral ventricle, and total white matter hyperintensity (WMH) volumes. Linear regression models tested associations between CVD risk and infarct with MRI outcomes and for modifications by age and sex. Sixty percent of participants were at medium or high CVD risk. Medium and high CVD risk were associated with lower total brain and frontal gray matter and higher WMH volumes compared to those with low CVD risk. High CVD risk was additionally associated with lower total cortical gray matter and parietal volumes and larger lateral ventricle volumes. Men tended to have greater CVDRF-related differences in total brain volumes than women. The association of CVD risk factors on total brain volumes increased with age, equal to an approximate 7-year increase in total brain aging among the high-CVD-risk group compared to the low-risk group. The presence of infarct(s) was associated with lower total brain volumes, which was equal to an approximate 5-year increase in brain aging compared to individuals without infarcts. Infarcts were also associated with smaller total cortical gray matter, frontal and parietal volumes, and larger lateral ventricle and WMH volumes. The high prevalence of CVD risk among Hispanic/Latino adults may be associated with accelerated brain aging.

The impact of sunlight exposure on brain structural markers in the UK Biobank

Sunlight is closely intertwined with daily life. It remains unclear whether there are associations between sunlight exposure and brain structural markers. General linear regression analysis was used to compare the differences in brain structural markers among different sunlight exposure time groups. Stratification analyses were performed based on sex, age, and diseases (hypertension, stroke, diabetes). Restricted cubic spline was performed to examine the dose–response relationship between natural sunlight exposure and brain structural markers, with further stratification by season. A negative association of sunlight exposure time with brain structural markers was found in the upper tertile compared to the lower tertile. Prolonged natural sunlight exposure was associated with the volumes of total brain (β: − 0.051, P < 0.001), white matter (β: − 0.031, P = 0.023), gray matter (β: − 0.067, P < 0.001), and white matter hyperintensities (β: 0.059, P < 0.001). These associations were more pronounced in males and individuals under the age of 60. The results of the restricted cubic spline analysis showed a nonlinear relationship between sunlight exposure and brain structural markers, with the direction changing around 2 h of sunlight exposure. This study demonstrates that prolonged exposure to natural sunlight is associated with brain structural markers change.

Juxtaventricular and periventricular white matter hyperintensities (WMH) are associated with cognitive dysfunction in Patients with Alzheimer’s Disease

Introduction White matter hyperintensities (WMH) is common among the elderly. WMH are associated with accelerated cognitive dysfunction and increased risk for Alzheimer`s disease (AD). Although WMHs play a key role in lowering the threshold for the clinical expression of dementia in AD-related pathology, the clinical significance of their location is not fully understood.Objectives The aim of this study was twofold: 1) To investigate the quantitative association between WMH and cognitive function in AD; 2) To investigate whether there is any difference in the association between subclassified WMH and cognitive function in AD.MethodsA total of 171 patients with AD underwent clinical evaluations including volumetric brain MRI study and neuropsychological tests using the CERAD-K neuropsychological assessment battery. WMH volume was calculated using automated quantification method with SPM and MATLAB image processing software. According to the distance from the lateral ventricular surface, WMH within 3 mm, WMH within 3-13 mm, and WMH over 13 mm were classified as juxtaventricular WMH (JVWMH), periventricular WMH (PVWMH) and deep WMH (DWMH), respectively. WMH volume data was logarithmically transformed because it was right-skewed.ResultsWMH volume in AD was 20.7 ± 18.2 ml. Total WMH volume was associated with poor performance in categorical verbal fluency test (p = 0.008) and word list memory test (p = 0.023). JVWMH volume was associated with poor performances on categorical verbal fluency test (p = 0.013) and forward digit span test (p = 0.037). PVWMH volume was associated with poor performances on categorical verbal fluency test (p = 0.011) and word list memory test (p = 0.021), whereas DWMH volume showed no association with cognitive tests. Total WMH and PVWMH volume were also related to Clinical Dementia Rating scale sum of boxes score (p=0.022).Image:ConclusionsGreater JVWMH and PVWMH are related with concurrent impairments in semantic memory and frontal function independent of the hippocampal volume. However, DWMH volume is not associated with any cognitive function. Only PVWMH among subclassified WMH are related to the severity of AD.Disclosure of InterestNone Declared