Longitudinal Association between White Matter Hyperintensities and White Matter Beta-Amyloid Deposition in Cognitively Unimpaired Elderly

2021 ◽  
Vol 18 ◽  
Author(s):  
Ming-Liang Wang ◽  
Meng-Meng Yu ◽  
Wen-Bin Li ◽  
Yue-Hua Li
Keyword(s):  
White Matter ◽  
White Matter Hyperintensities ◽  
Beta Amyloid ◽  
Standard Uptake Value ◽  
Amyloid Deposition ◽  
Cognitive Measures ◽  
Cross Sectional ◽  
Memory Decline ◽  
Annual Increase ◽  
Longitudinal Association

Background: White matter (WM) beta-amyloid uptake has been used as a reference region to calculate the cortical standard uptake value ratio (SUVr). However, white matter hyperintensities (WMH) may have an influence on WM beta-amyloid uptake. Our study aimed to investigate the associations between WMH and WM beta-amyloid deposition in cognitively unimpaired elderly. Method: Data from 83 cognitively unimpaired individuals in the Alzheimer’s Disease Neuroimag- ing Initiative (ADNI) dataset were analyzed. All participants had complete baseline and four-year follow-up information about WMH volume, WM 18F-AV-45 SUVr, and cognitive function, includ- ing ADNI-Memory (ADNI-Mem) and ADNI-Executive function (ADNI-EF) scores. Cross-sectional and longitudinal linear regression analyses were used to determine the associations between WMH and WM SUVr and cognitive measures. Results: Lower WM 18F-AV-45 SUVr at baseline was associated with younger age (β=0.01, P=0.037) and larger WMH volume (β=-0.049, P=0.048). The longitudinal analysis found an annual increase in WM 18F-AV-45 SUVr was associated with an annual decrease in WMH volume (β=-0.016, P=0.041). An annual decrease in the ADNI-Mem score was associated with an annual increase in WMH volume (β=-0.070, P=0.001), an annual decrease in WM 18F-AV-45 SUVr (β=0.559, P=0.030), and fewer years of education (β=0.011, P=0.044). There was no significant as- sociation between WM 18F-AV-45 SUVr and ADNI-EF (P>0.05). Conclusions: Reduced beta-amyloid deposition in WM was associated with higher WMH load and memory decline in cognitively unimpaired elderly. WMH volume should be considered when WM 18F-AV-45 SUVr is used as a reference for evaluating cortical 18F-AV-45 SUVr.

scholarly journals Differential Progression of Motor Dysfunction Between Male and Female Fragile X Premutation Carriers Reveals Novel Aspects of Sex-Specific Neural Involvement

2021 ◽  
Vol 7 ◽  
Author(s):  
Danuta Z. Loesch ◽  
Flora Tassone ◽  
Anna Atkinson ◽  
Paige Stimpson ◽  
Nicholas Trost ◽  
...  
Keyword(s):  
Sex Differences ◽  
White Matter ◽  
White Matter Hyperintensities ◽  
Fragile X ◽  
Cognitive Measures ◽  
Cross Sectional ◽  
Male And Female ◽  
Fragile X Premutation ◽  
Wide Range ◽  
Female Carriers

Expansions of the CGG repeat in the non-coding segment of the FMR1 X-linked gene are associated with a variety of phenotypic changes. Large expansions (>200 repeats), which cause a severe neurodevelopmental disorder, the fragile x syndrome (FXS), are transmitted from the mothers carrying smaller, unstable expansions ranging from 55 to 200 repeats, termed the fragile X premutation. Female carriers of this premutation may themselves experience a wide range of clinical problems throughout their lifespan, the most severe being the late onset neurodegenerative condition called “Fragile X-Associated Tremor Ataxia Syndrome” (FXTAS), occurring between 8 and 16% of these carriers. Male premutation carriers, although they do not transmit expanded alleles to their daughters, have a much higher risk (40–50%) of developing FXTAS. Although this disorder is more prevalent and severe in male than female carriers, specific sex differences in clinical manifestations and progress of the FXTAS spectrum have been poorly documented. Here we compare the pattern and rate of progression (per year) in three motor scales including tremor/ataxia (ICARS), tremor (Clinical Tremor Rating scale, CRST), and parkinsonism (UPDRS), and in several cognitive and psychiatric tests scores, between 13 female and 9 male carriers initially having at least one of the motor scores ≥10. Moreover, we document the differences in each of the clinical and cognitive measures between the cross-sectional samples of 21 female and 24 male premutation carriers of comparable ages with FXTAS spectrum disorder (FSD), that is, who manifest one or more features of FXTAS. The results of progression assessment showed that it was more than twice the rate in male than in female carriers for the ICARS-both gait ataxia and kinetic tremor domains and twice as high in males on the CRST scale. In contrast, sex difference was negligible for the rate of progress in UPDRS, and all the cognitive measures. The overall psychiatric pathology score (SCL-90), as well as Anxiety and Obsessive/Compulsive domain scores, showed a significant increase only in the female sample. The pattern of sex differences for progression in motor scores was consistent with the results of comparison between larger, cross-sectional samples of male and female carriers affected with the FSD. These results were in concert with sex-specific distribution of MRI T2 white matter hyperintensities: all males, but no females, showed the middle cerebellar peduncle white matter hyperintensities (MCP sign), although the distribution and severity of these hyperintensities in the other brain regions were not dissimilar between the two sexes. In conclusion, the magnitude and specific pattern of sex differences in manifestations and progression of clinically recorded changes in motor performance and MRI lesion distribution support, on clinical grounds, the possibility of certain sex-limited factor(s) which, beyond the predictable effect of the second, normal FMR1 alleles in female premutation carriers, may have neuroprotective effects, specifically concerning the cerebellar circuitry.

An Exploratory Study of Pathways from White Matter Hyperintensities to Cognitive Impairment through Depressive Symptoms Using Structural Equation Modeling: A Cross Sectional Study in Patients with Dementia

2020 ◽  
Vol 26 (7) ◽  
pp. 679-689
Author(s):  
Chang Hyun Lee ◽  
Do Hoon Kim
Keyword(s):  
Cognitive Impairment ◽  
Structural Equation Modeling ◽  
Depressive Symptoms ◽  
Cognitive Function ◽  
White Matter ◽  
Structural Equation ◽  
White Matter Hyperintensities ◽  
Mediating Effect ◽  
Equation Modeling ◽  
Cross Sectional

AbstractObjective:The aim of this study was to model the relationships among white matter hyperintensities (WMHs), depressive symptoms, and cognitive function and to examine the mediating effect of depressive symptoms on the relationship between WMHs and cognitive impairment.Methods:We performed structural equation modeling using cross-sectional data from 1158 patients from the Clinical Research for Dementia of South Korea (CREDOS) registry who were diagnosed with mild-to-moderate dementia. Periventricular white matter hyperintensities (PWMHs) and deep white matter hyperintensities (DWMHs) were obtained separately on the protocol of magnetic resonance imaging (MRI). Depression and cognitive function were assessed using the Korean Form of the Geriatric Depression Scale (KGDS) and the Seoul Neuropsychological Screening Battery (SNSB), respectively.Results:The model that best reflected the relationships among the variables was the model in which DWMHs affected cognitive function directly and indirectly through the depressive symptoms; on the other hand, PWMHs only directly affected cognitive function.Conclusions:This study presents the mediation model including the developmental pathway from DWMHs to cognitive impairment through depressive symptoms and suggests that the two types of WMHs may affect cognitive impairment through different pathways.

scholarly journals White matter hyperintensities and headache: A population-based imaging study (HUNT MRI)

Cephalalgia ◽  
2018 ◽  
Vol 38 (13) ◽  
pp. 1927-1939 ◽  
Author(s):  
Lasse-Marius Honningsvåg ◽  
Asta Kristine Håberg ◽  
Knut Hagen ◽  
Kjell Arne Kvistad ◽  
Lars Jacob Stovner ◽  
...  
Keyword(s):  
White Matter ◽  
Odds Ratio ◽  
White Matter Hyperintensities ◽  
Imaging Study ◽  
Population Based ◽  
Tension Type Headache ◽  
Health Study ◽  
Cross Sectional ◽  
Type Headache ◽  
New Onset

Objective To examine the relationship between white matter hyperintensities and headache. Methods White matter hyperintensities burden was assessed semi-quantitatively using Fazekas and Scheltens scales, and by manual and automated volumetry of MRI in a sub-study of the general population-based Nord-Trøndelag Health Study (HUNT MRI). Using validated questionnaires, participants were categorized into four cross-sectional headache groups: Headache-free (n = 551), tension-type headache (n = 94), migraine (n = 91), and unclassified headache (n = 126). Prospective questionnaire data was used to further categorize participants into groups according to the evolution of headache during the last 12 years: Stable headache-free, past headache, new onset headache, and persistent headache. White matter hyperintensities burden was compared across headache groups using adjusted multivariate regression models. Results Individuals with tension-type headache were more likely to have extensive white matter hyperintensities than headache-free subjects, with this being the case across all methods of white matter hyperintensities assessment (Scheltens scale: Odds ratio, 2.46; 95% CI, 1.44–4.20). Migraine or unclassified headache did not influence the odds of having extensive white matter hyperintensities. Those with new onset headache were more likely to have extensive white matter hyperintensities than those who were stable headache-free (Scheltens scale: Odds ratio, 2.24; 95% CI, 1.13–4.44). Conclusions Having tension-type headache or developing headache in middle age was linked to extensive white matter hyperintensities. These results were similar across all methods of assessing white matter hyperintensities. If white matter hyperintensities treatment strategies emerge in the future, this association should be taken into consideration.

White matter hyperintensities as a new predictor of driving cessation in the elderly

2017 ◽  
Vol 41 (S1) ◽  
pp. S172-S173 ◽  
Author(s):  
K.Y. Lim ◽  
S.J. Son ◽  
M. Jang ◽  
C.H. Hong
Keyword(s):  
White Matter ◽  
Sex Education ◽  
Cognitive Functions ◽  
White Matter Hyperintensities ◽  
Brain Mri ◽  
The Elderly ◽  
Motor Dysfunction ◽  
Driving Ability ◽  
Driving Cessation ◽  
Cross Sectional

Background/aimsMotor, perceptual, and cognitive functions affect driving competence. White matter hyperintensities (WMH) changes on brain MRI are associated structural brain changes along with cognitive and motor performance. The aim of this study was to investigate the association between WMH and driving ability in the elderly.MethodsParticipants (n = 540) were drawn from a nationwide, multicenter, hospital-based, longitudinal cohort study. Each participant underwent clinical evaluations, neuropsychological tests, and interview for caregiver including driving capacity, which was categorized as ‘now driving’, and ‘driving cessation (driving before, not now)’. A total 540 participants were divided into three groups (389 mild, 116 moderate, and 35 severe) depending on the degree of WMH. The same evaluations of them were followed after each year. The statistical analyses were performed using χ2 test, an analysis of variance (ANOVA), structured equation model (SEM), and generalized estimating equation (GEE).ResultsIn a SEM, greater baseline degree of WMH was directly associated with driving cessation regardless of cognitive and motor dysfunction (β = –0.110, P < 0.001). In GEE models controlling for age, sex, education, cognitive, and motor dysfunction, the more severe changes of the degree of WMH was associated with the faster change from ‘now driving’ state to ‘driving cessation’ state over time in the elderly (β = –0.508, P < 0.001).ConclusionIn both cross-sectional and longitudinal aspects, the degree of WMH might be one of the predictive factors for driving cessation in the elderly, reflecting both motor and cognitive functions or independently.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals Sweat the Fall Stuff: Physical Activity Moderates the Association of White Matter Hyperintensities With Falls Risk in Older Adults

2021 ◽  
Vol 15 ◽  
Author(s):  
Rachel A. Crockett ◽  
Ryan. S. Falck ◽  
Elizabeth Dao ◽  
Chun Liang Hsu ◽  
Roger Tam ◽  
...  
Keyword(s):  
Physical Activity ◽  
Older Adults ◽  
White Matter ◽  
White Matter Hyperintensities ◽  
Public Health Problem ◽  
Community Dwelling ◽  
Major Public Health Problem ◽  
Cross Sectional ◽  
Falls Risk ◽  
Experienced Radiologist

Background: Falls in older adults are a major public health problem. White matter hyperintensities (WMHs) are highly prevalent in older adults and are a risk factor for falls. In the absence of a cure for WMHs, identifying potential strategies to counteract the risk of WMHs on falls are of great importance. Physical activity (PA) is a promising countermeasure to reduce both WMHs and falls risk. However, no study has yet investigated whether PA attenuates the association of WMHs with falls risk. We hypothesized that PA moderates the association between WMHs and falls risk.Methods: Seventy-six community-dwelling older adults aged 70–80 years old were included in this cross-sectional study. We indexed PA using the Physical Activity Score for the Elderly (PASE) Questionnaire. Falls risk was assessed using the Physiological Profile Assessment (PPA), and WMH volume (mm3) was determined by an experienced radiologist on T2-weighted and PD-weighted MRI scans. We first examined the independent associations of WMH volume and PASE score with PPA. Subsequently, we examined whether PASE moderated the relationship between WMH volume and PPA. We plotted simple slopes to interpret the interaction effects. Age, sex, and Montreal Cognitive Assessment (MoCA) score were included as covariates in all models.Results: Participants had a mean age of 74 years (SD = 3 years) and 54 (74%) were female. Forty-nine participants (66%) had a Fazekas score of 1, 19 (26%) had a score of 2, and 6 (8%) a score of 3. Both PASE (β = −0.26 ± 0.11; p = 0.022) and WMH volume (β = 0.23 ± 0.11; p = 0.043) were each independently associated with PPA score. The interaction model indicated that PASE score moderated the association between WMH volume and PPA (β = −0.27 ± 0.12; p = 0.030), whereby higher PASE score attenuated the association between WMHs and falls risk.Conclusion: PA is an important moderator of falls risk. Importantly, older adults with WMH can reduce their risk of falls by increasing their PA.

Cerebral microbleeds and CSF Alzheimer biomarkers in primary progressive aphasias

Neurology ◽  
2018 ◽  
Vol 90 (12) ◽  
pp. e1057-e1065 ◽  
Author(s):  
Aline Mendes ◽  
Anne Bertrand ◽  
Foudil Lamari ◽  
Olivier Colliot ◽  
Alexandre Routier ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
White Matter ◽  
Alzheimer Disease ◽  
White Matter Hyperintensities ◽  
Primary Progressive Aphasia ◽  
Cerebral Microbleeds ◽  
Healthy Controls ◽  
Cross Sectional ◽  
Primary Progressive ◽  
Alzheimer Pathology

ObjectiveTo reveal the prevalence and localization of cerebral microbleeds (CMBs) in the 3 main variants of primary progressive aphasia (PPA) (logopenic, semantic, and nonfluent/agrammatic), to identify the relationship with underlying Alzheimer pathology, and to explore whether CMBs contribute to language breakdown.MethodsWe used a cross-sectional design in a multicenter cohort of 82 patients with PPA and 19 similarly aged healthy controls. MRI allowed for rating CMBs (2-dimensional gradient recalled echo T2*, susceptibility weighted imaging sequences) and white matter hyperintensities. CSF Alzheimer disease biomarker analyses available in 63 of the 82 patients provided the stratification of PPA into subgroups with patients who had or did not have probable underlying Alzheimer pathology.ResultsThe prevalence of CMBs was higher in patients with PPA (28%) than in controls (16%). They were more prevalent in logopenic PPA (50%) than in semantic PPA (18%) and nonfluent/agrammatic PPA (17%). The localization of CMBs was mainly lobar (81%) with no difference between the PPA variants. CMBs were more frequent in PPA patients with positive than with negative CSF Alzheimer disease biomarkers (67% vs 20%). Patients with and without lobar CMBs had similar volumes of white matter hyperintensities. Language and general cognitive impairment in PPA was unrelated to CMB rates.ConclusionsCMB prevalence in PPA is higher than in healthy controls. CMBs were most prevalent in the logopenic variant, were related to underlying Alzheimer pathology, and did not affect the language/cognitive impairment. Our findings also suggest that CMB detection with MRI contributes to PPA variant diagnosis, especially of logopenic PPA, and provides an estimator of the underlying neuropathology.

scholarly journals Coagulation factor VIII, white matter hyperintensities and cognitive function: Results from the Cardiovascular Health Study

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0242062
Author(s):  
Jessica L. Rohmann ◽  
W. T. Longstreth ◽  
Mary Cushman ◽  
Annette L. Fitzpatrick ◽  
Susan R. Heckbert ◽  
...  
Keyword(s):  
Cognitive Function ◽  
White Matter ◽  
White Matter Hyperintensities ◽  
Cardiovascular Health ◽  
Coagulation Factor ◽  
Health Study ◽  
Cardiovascular Health Study ◽  
Digit Symbol Substitution Test ◽  
Cross Sectional ◽  
Over Time

Objective To investigate the relationship between high FVIII clotting activity (FVIII:C), MRI-defined white matter hyperintensities (WMH) and cognitive function over time. Methods Data from the population-based Cardiovascular Health Study (n = 5,888, aged ≥65) were used. FVIII:C was measured in blood samples taken at baseline. WMH burden was assessed on two cranial MRI scans taken roughly 5 years apart. Cognitive function was assessed annually using the Modified Mini-Mental State Examination (3MSE) and Digit Symbol Substitution Test (DSST). We used ordinal logistic regression models adjusted for demographic and cardiovascular factors in cross-sectional and longitudinal WMH analyses, and adjusted linear regression and linear mixed models in the analyses of cognitive function. Results After adjustment for confounding, higher levels of FVIII:C were not strongly associated with the burden of WMH on the initial MRI scan (OR>p75 = 1.20, 95% CI 0.99–1.45; N = 2,735) nor with WMH burden worsening over time (OR>p75 = 1.18, 95% CI 0.87–1.59; N = 1,527). High FVIII:C showed no strong association with cognitive scores cross-sectionally (3MSE>p75 β = -0.06, 95%CI -0.45 to 0.32, N = 4,005; DSST>p75 β = -0.69, 95%CI -1.52 to 0.13, N = 3,954) or over time (3MSE>p75 β = -0.07,95% CI -0.58 to 0.44, N = 2,764; DSST>p75 β = -0.22, 95% CI -0.97 to 0.53, N = 2,306) after confounding adjustment. Interpretation The results from this cohort study of older adult participants indicate no strong relationships between higher FVIII:C levels and WMH burden or cognitive function in cross-sectional and longitudinal analyses.

scholarly journals Association between Deep White Matter Hyperintensities and Right-to-left Shunt in Migraine (CAMBRAIN): A Cross-sectional Multicenter Study

2021 ◽  
Author(s):  
Yingqi Xing ◽  
YiShui Zhang ◽  
HongLing Zhao ◽  
SiBo Wang ◽  
YingHua Cui ◽  
...  
Keyword(s):  
White Matter ◽  
White Matter Hyperintensities ◽  
Cross Sectional Study ◽  
Sectional Study ◽  
Resonance Imaging ◽  
Cross Sectional ◽  
Contrast Enhanced ◽  
Weighted Magnetic Resonance Imaging ◽  
Independent Risk Factors ◽  
Magnetic Resonance Imaging Mri

Abstract BackgroundDeep white matter hyperintensities (DWMHs), often identified by hyperintense lesions on T2-weighted magnetic resonance imaging (MRI), were discovered to have a higher prevalence in migraine patients. A right-to-left shunt (RLS), which is also prevalent in migraineurs, could potentially contribute to the formation of DWMHs by induction of controversial embolism and endothelial dysfunction. In this cross-sectional study, we aim to evaluate the association between RLS and the prevalence of DWMHs in patients with migraine.MethodsIn this study, we consecutively enrolled patients with migraine aged between 18 and 50 years from the 14 headache clinics of participating hospitals. DWMHs were rated using Scheltens scale on digital MRI images obtained from 1.5T scanners, and RLS was detected via contrast-enhanced transcranial Doppler. Analyses on DWMH prevalence and loads by RLS grading or subtype were performed. A logistic regression analysis on DWMH prevalence was also performed.ResultsIn all, 237 migraine patients (age: 39.3 ± 11.7, 78.1% women, 13% migraine with aura) were enrolled. RLS was detected in 48.5% of the subjects and DWMHs were identified in 138 (58.2%) patients. Prevalence of DWMHs did not differ significantly between RLS+ (57.4%) and RLS− patients (59.0%, p = 0.74). No statistical difference in DWMH loads was found between different RLS grades or subtypes. Instead of RLS grades (p = 0.75), age (OR 1.067; 95%CI 1.034–1.101; p < 0.001) and aura (OR 4.063; 95%CI 1.492–11.061; p = 0.006) were statistically significant independent risk factors for increased DWMH prevalence in migraine patients.ConclusionsOur findings do not support an association between RLS and DWMHs in migraine patients, regardless of RLS grades or subtypes.Clinical Trial Registration: NCT 03418766; Date of registration: February 1, 2018

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