Abstract P121: Twenty-two-year Cognitive Decline Was Significantly Associated With Vascular And Neurodegenerative Brain Changes In The Aric Neurocognitive Study

Circulation ◽  
2021 ◽  
Vol 143 (Suppl_1) ◽  
Author(s):  
Alessandro Orlando ◽  
A Richey Sharrett ◽  
Rebecca F Gottesman ◽  
David Knopman ◽  
Andrea L Schneider ◽  
...  
Keyword(s):  
White Matter ◽  
Brain Imaging ◽  
Temporal Lobe ◽  
Brain Volume ◽  
Brain Mri ◽  
Amyloid Deposition ◽  
White Matter Hyperintensity ◽  
Β Amyloid ◽  
The Mean

Introduction: Studies have found that smaller brain volumes, cerebral infarcts, and white matter abnormalities are associated with dementia and mild cognitive impairment. However, these studies have been limited by short follow-up precluding a strong establishment of temporality. Therefore, it is unknown whether brain imaging findings are preceded by long-term changes in cognition. We sought to address this gap by examining brain imaging and two decades of cognitive changes in and a large, representative population-based cohort of older adults of black and white race. Hypothesis: We hypothesized that 22-year declines in global cognitive factor scores (GCFS) would be associated with a pattern of smaller total brain and temporal lobe meta region of interest (likely to be affected by Alzheimer’s disease) volumes, larger white matter hyperintensity volumes, and greater odds of ≥1 lacunar infarct and elevated brain β-amyloid deposition. Methods: ARIC participants with brain imaging data, complete cognitive factor score, and not missing key covariates were included. GCFS were collected at three visits across 22 years (1990-2013), and brain MRI and florbetapir PET imaging were collected in 2011-13; PET in subset of n=327. Mixed effects models with random intercepts and slopes predicted individual change in GCFS. Outcomes of interest were total brain volume (cc), temporal lobe meta region volume, log 2 (white matter hyperintensity volume), ≥1 lacunar infarct, and elevated brain β-amyloid deposition (SUVR >1.2). Multivariable linear and logistic regression was used to relate outcomes to GCFS slopes after adjusting for confounders, including vascular risk factors. As appropriate, models were also adjusted for total intracranial volume. Results: Among 1957 with complete brain MRI imaging, 1830 were included in the study, 60% (n=1096) women and 26% (n=480) black. At the first visit, the mean (SD) baseline age was 55 (5.2) yrs. The mean (SD) observed GCFS at the three visits were 0.16 (0.79), 0.05 (0.75), and -0.78 (0.86). After adjustment, a 1-SD larger decline in GCFS was significantly associated with a smaller brain volume by 1.6% [95%CI: 1.3, 1.8] relative to mean brain volume, a smaller temporal lobe meta region volume by 2.4% [2.1, 2.8] relative to the mean volume, a 15% [11, 19] larger volume of white matter hyperintensities, 1.3-fold [1.2, 1.4] higher odds of having ≥1 lacune, and 1.8-fold [1.4, 2.4] higher odds of elevated brain β-amyloid deposition. Associations remained significant after further adjustment for first or last GCFS. Conclusions: Greater declines in long-term cognitive functioning were significantly associated with smaller brain volumes and dementia-related brain characteristics and were independent of last visit GCFS. This suggests long-term changes in cognition may precede late-life brain morphology and outperform cross-sectional cognitive measures.

scholarly journals Association of White Matter Hyperintensity Markers on MRI and Long-term Risk of Mortality and Ischemic Stroke

Neurology ◽  
2021 ◽  
Vol 96 (17) ◽  
pp. e2172-e2183 ◽  
Author(s):  
Rashid Ghaznawi ◽  
Mirjam I. Geerlings ◽  
Myriam Jaarsma-Coes ◽  
Jeroen Hendrikse ◽  
Jeroen de Bresser ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
White Matter ◽  
Cox Regression ◽  
Brain Mri ◽  
Arterial Disease ◽  
White Matter Hyperintensity ◽  
Risk Of Mortality ◽  
Mri Scans

ObjectiveTo determine whether white matter hyperintensity (WMH) markers on MRI are associated with long-term risk of mortality and ischemic stroke.MethodsWe included consecutive patients with manifest arterial disease enrolled in the Second Manifestations of Arterial Disease–Magnetic Resonance (SMART-MR) study. We obtained WMH markers (volume, type, and shape) from brain MRI scans performed at baseline using an automated algorithm. During follow-up, occurrence of death and ischemic stroke was recorded. Using Cox regression, we investigated associations of WMH markers with risk of mortality and ischemic stroke, adjusting for demographics, cardiovascular risk factors, and cerebrovascular disease.ResultsWe included 999 patients (59 ± 10 years; 79% male) with a median follow-up of 12.5 years (range 0.2–16.0 years). A greater periventricular or confluent WMH volume was independently associated with a greater risk of vascular death (hazard ratio [HR] 1.29, 95% confidence interval [CI] 1.13–1.47) for a 1-unit increase in natural log-transformed WMH volume and ischemic stroke (HR 1.53, 95% CI 1.26–1.86). A confluent WMH type was independently associated with a greater risk of vascular (HR 1.89, 95% CI 1.15-3.11) and nonvascular death (HR 1.65, 95% CI 1.01–2.73) and ischemic stroke (HR 2.83, 95% CI 1.36-5.87). A more irregular shape of periventricular or confluent WMH, as expressed by an increase in concavity index, was independently associated with a greater risk of vascular (HR 1.20, 95% CI 1.05–1.38 per SD increase) and nonvascular death (HR 1.21, 95% CI 1.03–1.42) and ischemic stroke (HR 1.28, 95% CI 1.05–1.55).ConclusionsWMH volume, type, and shape are associated with long-term risk of mortality and ischemic stroke in patients with manifest arterial disease.

Abstract WP192: Periventricular White Matter Hyperintensities Are Associated With Functional Decline: The Northern Manhattan Study

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Mandip S Dhamoon ◽  
Ying-Kuen Cheung ◽  
Ahmet M Bagci ◽  
Chensy Marquez ◽  
Noam Alperin ◽  
...  
Keyword(s):  
White Matter ◽  
Repeated Measures ◽  
Brain Mri ◽  
Large Population ◽  
Functional Decline ◽  
Brain Regions ◽  
White Matter Hyperintensity ◽  
Periventricular White Matter ◽  
Brain White Matter

Background: We previously showed that overall brain white matter hyperintensity volume (WMHV) was associated with accelerated long-term functional decline. However, it was unclear whether WMHV in particular brain regions was more predictive of decline. We hypothesized that WMHV in particular brain regions would be more predictive of functional decline. Methods: In the Northern Manhattan MRI study, participants had brain MRI with axial T1, T2, and fluid attenuated inversion recovery sequences, with baseline interview and examination. Volumetric WMHV distribution across 14 brain regions (brainstem, cerebellum, and bilateral frontal, occipital, temporal, and parietal lobes, and bilateral anterior and posterior periventricular white matter [PVWM]) was determined separately by combining bimodal image intensity distribution and atlas based methods. Participants had annual functional assessments with the Barthel index (BI, range 0-100) over a mean of 7.3 years and were followed for stroke and myocardial infarction (MI). Due to multiple collinear variables, lasso regression was used to select regional WMHV variables, and adjusted generalized estimating equations models estimated associations with baseline BI and change over time. Results: Among 1195 participants, mean age was 71 (SD 9) years, 460 (39%) were male, 802 (67%) had hypertension and 224 (19%) diabetes. Using lasso regularization, only right anterior PVWM was selected, and each SD increase was associated with accelerated functional decline, of -0.95 additional BI points per year (95% CI -1.20, -0.70) in an unadjusted model, -0.92 points per year (95% CI -1.18, -0.67) with baseline covariate adjustment, and -0.87 points per year (95% CI -1.12, -0.62) after adjusting for stroke and MI. This decline was in addition to a mean decline of -1.13 (95% CI -1.29, -0.97), -1.19 (95% CI -1.36, -1.01), and -1.04 (95% CI -1.21, -0.88) BI points per year, respectively. Conclusions: In this large population-based study with long-term repeated measures of function, periventricular WMHV was particularly associated with accelerated functional decline. Periventricular WMHV may have a greater effect on mobility due to dysfunction in descending leg motor tracts.

scholarly journals Circulating cortisol and cognitive and structural brain measures

Neurology ◽  
2018 ◽  
Vol 91 (21) ◽  
pp. e1961-e1970 ◽  
Author(s):  
Justin B. Echouffo-Tcheugui ◽  
Sarah C. Conner ◽  
Jayandra J. Himali ◽  
Pauline Maillard ◽  
Charles S. DeCarli ◽  
...  
Keyword(s):  
White Matter ◽  
Visual Perception ◽  
Gray Matter ◽  
Brain Volume ◽  
Brain Mri ◽  
Serum Cortisol ◽  
Community Dwelling ◽  
White Matter Hyperintensity ◽  
Middle Aged ◽  
Middle Aged Adults

ObjectiveTo assess the association of early morning serum cortisol with cognitive performance and brain structural integrity in community-dwelling young and middle-aged adults without dementia.MethodsWe evaluated dementia-free Framingham Heart Study (generation 3) participants (mean age 48.5 years, 46.8% men) who underwent cognitive testing for memory, abstract reasoning, visual perception, attention, and executive function (n = 2,231) and brain MRI (n = 2018) to assess total white matter, lobar gray matter, and white matter hyperintensity volumes and fractional anisotropy (FA) measures. We used linear and logistic regression to assess the relations of cortisol (categorized in tertiles, with the middle tertile as referent) to measures of cognition, MRI volumes, presence of covert brain infarcts and cerebral microbleeds, and voxel-based microstructural white matter integrity and gray matter density, adjusting for age, sex, APOE, and vascular risk factors.ResultsHigher cortisol (highest tertile vs middle tertile) was associated with worse memory and visual perception, as well as lower total cerebral brain and occipital and frontal lobar gray matter volumes. Higher cortisol was associated with multiple areas of microstructural changes (decreased regional FA), especially in the splenium of corpus callosum and the posterior corona radiata. The association of cortisol with total cerebral brain volume varied by sex (p for interaction = 0.048); higher cortisol was inversely associated with cerebral brain volume in women (p = 0.001) but not in men (p = 0.717). There was no effect modification by the APOE4 genotype of the relations of cortisol and cognition or imaging traits.ConclusionHigher serum cortisol was associated with lower brain volumes and impaired memory in asymptomatic younger to middle-aged adults, with the association being evident particularly in women.

scholarly journals Hemoglobin and anemia in relation to dementia risk and accompanying changes on brain MRI

Neurology ◽  
2019 ◽  
Vol 93 (9) ◽  
pp. e917-e926 ◽  
Author(s):  
Frank J. Wolters ◽  
Hazel I. Zonneveld ◽  
Silvan Licher ◽  
Lotte G.M. Cremers ◽  
M. Kamran Ikram ◽  
...  
Keyword(s):  
White Matter ◽  
Cerebral Perfusion ◽  
Brain Mri ◽  
Structural Connectivity ◽  
Mean Diffusivity ◽  
Population Based ◽  
White Matter Hyperintensity ◽  
Dementia Risk ◽  
Increased Risk

ObjectiveTo determine the long-term association of hemoglobin levels and anemia with risk of dementia, and explore underlying substrates on brain MRI in the general population.MethodsSerum hemoglobin was measured in 12,305 participants without dementia of the population-based Rotterdam Study (mean age 64.6 years, 57.7% women). We determined risk of dementia and Alzheimer disease (AD) (until 2016) in relation to hemoglobin and anemia. Among 5,267 participants without dementia with brain MRI, we assessed hemoglobin in relation to vascular brain disease, structural connectivity, and global cerebral perfusion.ResultsDuring a mean follow-up of 12.1 years, 1,520 individuals developed dementia, 1,194 of whom had AD. We observed a U-shaped association between hemoglobin levels and dementia (p = 0.005), such that both low and high hemoglobin levels were associated with increased dementia risk (hazard ratio [95% confidence interval (CI)], lowest vs middle quintile 1.29 [1.09–1.52]; highest vs middle quintile 1.20 [1.00–1.44]). Overall prevalence of anemia was 6.1%, and anemia was associated with a 34% increased risk of dementia (95% CI 11%–62%) and 41% (15%–74%) for AD. Among individuals without dementia with brain MRI, similar U-shaped associations were seen of hemoglobin with white matter hyperintensity volume (p = 0.03), and structural connectivity (for mean diffusivity, p < 0.0001), but not with presence of cortical and lacunar infarcts. Cerebral microbleeds were more common with anemia. Hemoglobin levels inversely correlated to cerebral perfusion (p < 0.0001).ConclusionLow and high levels of hemoglobin are associated with an increased risk of dementia, including AD, which may relate to differences in white matter integrity and cerebral perfusion.

scholarly journals Long-Term Exposure to Fine Particulate Matter, Residential Proximity to Major Roads and Measures of Brain Structure

Stroke ◽  
2015 ◽  
Vol 46 (5) ◽  
pp. 1161-1166 ◽  
Author(s):  
Elissa H. Wilker ◽  
Sarah R. Preis ◽  
Alexa S. Beiser ◽  
Philip A. Wolf ◽  
Rhoda Au ◽  
...  
Keyword(s):  
Air Pollution ◽  
White Matter ◽  
Confidence Interval ◽  
Brain Volume ◽  
Brain Aging ◽  
Ambient Air ◽  
Ambient Air Pollution ◽  
White Matter Hyperintensity ◽  
Brain Infarcts

Background and Purpose— Long-term exposure to ambient air pollution is associated with cerebrovascular disease and cognitive impairment, but whether it is related to structural changes in the brain is not clear. We examined the associations between residential long-term exposure to ambient air pollution and markers of brain aging using magnetic resonance imaging. Methods— Framingham Offspring Study participants who attended the seventh examination were at least 60 years old and free of dementia and stroke were included. We evaluated associations between exposures (fine particulate matter [PM 2.5 ] and residential proximity to major roadways) and measures of total cerebral brain volume, hippocampal volume, white matter hyperintensity volume (log-transformed and extensive white matter hyperintensity volume for age), and covert brain infarcts. Models were adjusted for age, clinical covariates, indicators of socioeconomic position, and temporal trends. Results— A 2-μg/m 3 increase in PM 2.5 was associated with −0.32% (95% confidence interval, −0.59 to −0.05) smaller total cerebral brain volume and 1.46 (95% confidence interval, 1.10 to 1.94) higher odds of covert brain infarcts. Living further away from a major roadway was associated with 0.10 (95% confidence interval, 0.01 to 0.19) greater log-transformed white matter hyperintensity volume for an interquartile range difference in distance, but no clear pattern of association was observed for extensive white matter. Conclusions— Exposure to elevated levels of PM 2.5 was associated with smaller total cerebral brain volume, a marker of age-associated brain atrophy, and with higher odds of covert brain infarcts. These findings suggest that air pollution is associated with insidious effects on structural brain aging even in dementia- and stroke-free persons.

Biological Signatures of Alzheimer’s Disease

2020 ◽  
Vol 20 (9) ◽  
pp. 770-781 ◽  
Author(s):  
Poornima Sharma ◽  
Anjali Sharma ◽  
Faizana Fayaz ◽  
Sharad Wakode ◽  
Faheem H. Pottoo
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
White Matter ◽  
Senile Plaque ◽  
Senile Plaques ◽  
Amyloid Deposition ◽  
Immune Defense ◽  
Amyloid Angiopathy ◽  
Microvascular Changes ◽  
Β Amyloid

Alzheimer’s disease (AD) is the most prevalent and severe neurodegenerative disease affecting more than 0.024 billion people globally, more common in women as compared to men. Senile plaques and amyloid deposition are among the main causes of AD. Amyloid deposition is considered as a central event which induces the link between the production of β amyloid and vascular changes. Presence of numerous biomarkers such as cerebral amyloid angiopathy, microvascular changes, senile plaques, changes in white matter, granulovascular degeneration specifies the manifestation of AD while an aggregation of tau protein is considered as a primary marker of AD. Likewise, microvascular changes, activation of microglia (immune defense system of CNS), amyloid-beta aggregation, senile plaque and many more biomarkers are nearly found in all Alzheimer’s patients. It was seen that 70% of Alzheimer’s cases occur due to genetic factors. It has been reported in various studies that apolipoprotein E(APOE) mainly APOE4 is one of the major risk factors for the later onset of AD. Several pathological changes also occur in the white matter which include dilation of the perivascular space, loss of axons, reactive astrocytosis, oligodendrocytes and failure to drain interstitial fluid. In this review, we aim to highlight the various biological signatures associated with the AD which may further help in discovering multitargeting drug therapy.

The Clinical Value of Periventricular White Matter Hyperintensity on MRI in Sudden Sensorineural Hearing Loss

2021 ◽  
pp. 000348942110189
Author(s):  
Jung Woo Lee ◽  
Deoksu Kim ◽  
Seokhwan Lee ◽  
Sung-Won Choi ◽  
Soo-Keun Kong ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Multivariate Analysis ◽  
White Matter ◽  
Brain Mri ◽  
Sudden Sensorineural Hearing Loss ◽  
White Matter Hyperintensity ◽  
Control Group ◽  
Periventricular White Matter ◽  
Clinical Value ◽  
Hearing Gain

Objectives: To assess the clinical value of periventricular white matter hyperintensity (PWMH) found on brain magnetic resonance imaging (MRI) in patients with sudden sensorineural hearing loss (SSNHL). Methods: In this prospective study, 115 patients who were diagnosed with SSNHL aged between 55 and 75 years were analyzed. All subjects underwent brain MRI and were divided into a PWMH and control groups, depending on the presence of PWMH on MRI. PWMH was subdivided into 3 groups according to severity. Pure-tone average results and hearing gain were compared between the 2 groups before treatment and 2 months after treatment. Hearing improvement was assessed using Sigel’s criteria. Results: A total of 106 patients (43 in the PWMH group and 63 in the control group) finally completed the 2-month follow-up. Average hearing gain in the PWMH group was significantly higher than in the control group (34.8 ± 20.3 and 25.9 ± 20.3, respectively, P = .029). PWMH score 1 showed significantly better hearing levels and hearing gain compared to PWMH score 3 and the control group. Multivariate analysis revealed that younger age, better initial hearing level, and the presence of PVWM score 1 were associated with good recovery. Conclusions: The presence of PWMH score 1 on brain MRI in patients with SSNHL was associated with better treatment response and was a good prognostic factor in a multivariate analysis while the hearing recovery in more severe PWMH (scores 2, 3) was not different from the control group.

Progress of leukoaraiosis is inhibited by correction of platelet hyper-aggregability

2005 ◽  
Vol 17 (4) ◽  
pp. 689-698 ◽  
Author(s):  
Shigekiyo Fujita ◽  
Tetsuro Kawaguchi ◽  
Toshiyuki Uehara ◽  
Kazuhito Fukushima
Keyword(s):  
Group Versus ◽  
Adenosine Diphosphate ◽  
White Matter Hyperintensity ◽  
Number Of Patients ◽  
Mri Scans ◽  
The Mean ◽  
The Difference ◽  
Magnetic Resonance Imaging Mri ◽  
Observation Period

Background: Platelet hyper-aggregability is an important risk factor for leukoaraiosis. In this study we investigated whether aggravation of leukoaraiosis can be controlled by means of long-term correction of platelet hyper-aggregability.Methods:Twenty-one patients with leukoaraiosis and uncorrected platelet hyper-aggregability were compared with 21 controls matched for age, grade of leukoaraiosis and observation period whose platelet hyper-aggregability was corrected. Platelet aggregability was estimated by an optical analytical method with a nine-stage display using two different concentrations each of adenosine diphosphate (ADP) and collagen (the double ADP method).Results:The mean observation period between two magnetic resonance imaging (MRI) scans for both groups was 4.1 years. In the non-corrected group, moderate to severe aggravation of leukoaraiosis was observed in a large number of patients. In the corrected group, only a small number of patients showed generally mild aggravation of leukoaraiosis. The number of patients showing aggravation of periventricular hyperintensity (PVH) was 7 in 21 in the non-corrected group versus 1 in 21 (p=0.022) in the corrected group, and for aggravation of deep white-matter hyperintensity, these values were 9 in 21 versus 4 in 21, respectively. Thus, the difference was more significant if the degree of aggravation was taken into account.Conclusion:The progress of leukoaraiosis is greatly inhibited by long-term correction of platelet hyper-aggregability.

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