scholarly journals Olfactory testing does not predict β-amyloid, MRI measures of neurodegeneration or vascular pathology in the British 1946 birth cohort

2020 ◽  
Vol 267 (11) ◽  
pp. 3329-3336
Author(s):  
Sarah M. Buchanan ◽  
Thomas D. Parker ◽  
Christopher A. Lane ◽  
Ashvini Keshavan ◽  
Sarah E. Keuss ◽  
...  
Keyword(s):  
White Matter ◽  
Birth Cohort ◽  
Entorhinal Cortex ◽  
Cortical Thickness ◽  
White Matter Hyperintensity ◽  
Amyloid Pet ◽  
Brain Health ◽  
Cognitively Normal ◽  
Olfactory Identification ◽  
Β Amyloid

Abstract Objective To explore the value of olfactory identification deficits as a predictor of cerebral β-amyloid status and other markers of brain health in cognitively normal adults aged ~ 70 years. Methods Cross-sectional observational cohort study. 389 largely healthy and cognitively normal older adults were recruited from the MRC National Survey of Health and Development (1946 British Birth cohort) and investigated for olfactory identification deficits, as measured by the University of Pennsylvania Smell Identification Test. Outcome measures were imaging markers of brain health derived from 3 T MRI scanning (cortical thickness, entorhinal cortex thickness, white matter hyperintensity volumes); 18F florbetapir amyloid-PET scanning; and cognitive testing results. Participants were assessed at a single centre between March 2015 and January 2018. Results Mean (± SD) age was 70.6 (± 0.7) years, 50.8% were female. 64.5% had hyposmia and 2.6% anosmia. Olfaction showed no association with β-amyloid status, hippocampal volume, entorhinal cortex thickness, AD signature cortical thickness, white matter hyperintensity volume, or cognition. Conclusion and relevance In the early 70s, olfactory function is not a reliable predictor of a range of imaging and cognitive measures of preclinical AD. Olfactory identification deficits are not likely to be a useful means of identifying asymptomatic amyloidosis. Further studies are required to assess if change in olfaction may be a proximity marker for the development of cognitive impairment.

scholarly journals P3-367: WHITE MATTER HYPERINTENSITY AND β-AMYLOID BURDEN IN A PRECLINICAL COGNITIVELY NORMAL COHORT

2019 ◽  
Vol 15 ◽  
pp. P1087-P1087
Author(s):  
Kaikai Shen ◽  
Pratishtha Chatterjee ◽  
Ying Xia ◽  
Kathryn Goozee ◽  
Jurgen Fripp ◽  
...  
Keyword(s):  
White Matter ◽  
White Matter Hyperintensity ◽  
Amyloid Burden ◽  
Cognitively Normal ◽  
Β Amyloid

scholarly journals Race and ethnicity-related differences in neuroimaging markers of neurodegeneration and cerebrovascular disease in middle and older age

2021 ◽  
Author(s):  
Indira C. Turney ◽  
Patrick J. Lao ◽  
Miguel Arce Rentería ◽  
Kay Igwe ◽  
Joncarlos Berroa ◽  
...  
Keyword(s):  
White Matter ◽  
Cerebrovascular Disease ◽  
Racial Disparities ◽  
Cortical Thickness ◽  
Race And Ethnicity ◽  
Ethnic Disparities ◽  
White Matter Hyperintensity ◽  
Racial And Ethnic Disparities ◽  
Brain Health ◽  
Washington Heights

ABSTRACTINTRODUCTIONNumerous neuroimaging studies demonstrated racial and ethnic disparities in brain health at older ages. It remains unclear whether racial and ethnic disparities increase with aging and whether they are already apparent in midlife.METHODSWe investigated differences in MRI markers of aging and cerebrovascular disease in 969 participants from the Washington Heights-Inwood Columbia Aging Project (WHICAP; mean age: 75 years) and 496 participants from the Offspring study (mean age: 55 years) across race and ethnicity (white, Black, Latinx).RESULTSOlder whites had greater cortical thickness compared with Latinxs, who also had greater thickness than Blacks. Cortical thickness was similar across race in the middle-aged cohort. Regarding white matter hyperintensity (WMH) volume, Blacks had disproportionately greater WMH volume compared to both whites and Latinxs at older ages. Racial disparities are already apparent in midlife, where Blacks have disproportionately greater WMH than whites.DiscussionThese findings suggest that racial disparities in WMH volume are already apparent in midlife.

Abstract MP16: Excessive White Matter Hyperintensity Burden and Functional Outcomes After Acute Ischemic Stroke

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Sungmin Hong ◽  
Anne-katrin Giese ◽  
Markus D Schirmer ◽  
Adrian V Dalca ◽  
Anna Bonkhoff ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
White Matter ◽  
Acute Ischemic Stroke ◽  
Functional Outcomes ◽  
Life Time ◽  
Stroke Recovery ◽  
White Matter Hyperintensity ◽  
Brain Health ◽  
Stroke Outcomes ◽  
The Brain

Objective: Ability of the brain to recover after an acute ischemic stroke (AIS) is linked to the pre-stroke burden of white matter hyperintensity (WMH), a radiographic marker of brain health. We sought to determine the excessive WMH burden in an AIS population and investigate its association with 3-month stroke outcomes. Data: We used 2,435 subjects from the MRI-GENIE study. Three-month functional outcomes of 872 subjects among those subjects were measured by 90-day modified Ranking Scale (mRS). Methods: We automatically quantified WMH volume (WMHv) on FLAIR images and adjusted for a brain volume. We modeled a trend using the factor analysis (FA) log-linear regression using age, sex, atrial fibrillation, diabetes, hypertension, coronary artery disease and smoking as input variables. We categorized three WMH burden groups based on the conditional probability given by the model (LOW: lower 33%, MED: middle 34%, and HIGH: upper 33%). The subgroups were compared with respect to mRS (median and dichotomized odds ratio (OR) (good/poor: mRS 0-2/3-6)). Results: Five FA components out of seven with significant relationship to WMHv (p<0.001) were used for the regression modeling (R 2 =0.359). The HIGH group showed higher median (median=2, IQR=2) mRS score than LOW (median=1, IQR=1) and MED (median=1, IQR=1). The odds (OR) of good AIS outcome for LOW and MED were 1.8 (p=0.0001) and 1.6 (p=0.006) times higher than HIGH, respectively. Conclusion: Once accounted for clinical covariates, the excessive WMHv was associated with worse 3-month stroke outcomes. These data suggest that a life-time of injury to the white matter reflected in WMH is an important factor for stroke recovery and an indicator of the brain health.

Abstract 47: White Matter Atrophy in Cerebral Amyloid Angiopathy

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Panagiotis Fotiadis ◽  
Aaron Schultz ◽  
Trey Hedden ◽  
Sergi Martinez-Ramirez ◽  
Yael Reijmer ◽  
...  
Keyword(s):  
White Matter ◽  
Cerebral Amyloid Angiopathy ◽  
Cortical Thickness ◽  
Tissue Loss ◽  
White Matter Hyperintensity ◽  
Aging Brain ◽  
Amyloid Angiopathy ◽  
Intracranial Volume ◽  
White Matter Volume ◽  
Cerebral Amyloid

Background/Purpose: Cerebral Amyloid Angiopathy (CAA) leads to leukoaraiosis, lacunar infarcts and cortical tissue loss. We hypothesized that CAA is also associated with white matter atrophy (WMA). Methods: We have compared volumetric multimodal MRIs from 72 prospectively enrolled non-demented patients with probable CAA (per Boston criteria), to 3 other well-studied cohorts: 289 Healthy Controls (HC) from the Harvard Aging Brain (HAB) study, 231 HC and 198 patients with AD from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Validated FreeSurfer algorithms were used to calculate White Matter Volume (WMV), white matter hyperintensity volume (WMHv), and cortical thickness. Microbleeds (MBs) were counted on SWI-MRI. Measures were obtained from the contralateral hemisphere if intracerebral hemorrhage present. All volumes were corrected for total intracranial volume (ICV), so reported as percent of ICV. Results: The CAA patients were significantly younger (mean age: 70.1) compared to both HC cohorts (ADNI-HC: 76.0, p<0.001, HAB-HC: 73.8, p < 0.001), and to patients with AD (75.5, p < 0.001). Despite being younger, patients with CAA presented significantly lower global WMV (28% ± 2.6) than both ADNI-HC (29.2% ± 2.2, p < 0.001), HAB-HC (29.0% ± 2.5, p = 0.001), and patients with AD (28.7% ± 2.2, p = 0.02) [Figure]. The association persisted after correcting for age, gender and WMHv. Within the CAA cohort, there was a negative correlation between WMV and lobar MB counts (rho = -0.26, p = 0.03), it remained significant after correcting for age, gender, WMHv (p=0.016). There were no significant associations however between WMV and neither WMHv, nor cortical thickness (both p>0.2). Conclusions: Patients with CAA show WMA when compared to older HC and AD. WMA independently correlates with MBs, a marker of CAA severity. Consistent spatial patterns of atrophy especially in posterior regions when compared to both HC and AD [Figure] might represent the “WMA signature of CAA”.

488 GRIP STRENGTH FROM MIDLIFE AS AN INDICATOR OF LATER-LIFE COGNITION AND BRAIN HEALTH: EVIDENCE FROM A BRITISH BIRTH COHORT

2021 ◽  
Vol 50 (Supplement_2) ◽  
pp. ii5-ii7
Author(s):  
Q Dercon ◽  
J Nicholas ◽  
S-N James ◽  
J Schott ◽  
M Richards
Keyword(s):  
Grip Strength ◽  
Birth Cohort ◽  
Reference Group ◽  
Later Life ◽  
White Matter Hyperintensity ◽  
Birth Cohort Study ◽  
Brain Health ◽  
Average Maximum ◽  
Maximum Grip Strength ◽  
Maximum Grip

Abstract Introduction Grip strength is an objective measure of physical function with potential predictive value for health in ageing populations. We aimed to assess whether levels and changes in grip strength from midlife predicted later-life brain health and cognition. Methods 446 participants in an ongoing British birth cohort study, the MRC National Survey of Health and Development (NSHD), had their maximum grip strength measured at ages 53, 60–64, and 69, and underwent neuroimaging as part of its neuroscience sub-study, Insight 46, at 69–71. A group-based trajectory model identified latent groups of individuals in the whole NSHD cohort with below- and above-average grip strength over time, plus a reference group. Trajectory group membership, plus standardised grip strength levels and change from age 53, were each related to MRI-derived measures of whole-brain volume (WBV) and white-matter hyperintensity volume (WMHV), plus several cognitive tests. Models were adjusted for sex, body size, head size (where appropriate), sociodemographics, and behavioural and vascular risk factors. Results Consistently below-average grip strength from midlife was associated with lower WBV and non-verbal reasoning ability at age 69–71 (e.g. low group WBV vs. reference group β = −13.38 cm^3; 95% CI = (−24.12 cm^3, −2.64 cm^3); p = 0.015). There was some accompanying evidence that above-average maximum grip strength showed a positive association with WBV, which was more pronounced in female participants (high group female WBV vs. reference group β = 18.30 cm^3; 95% CI = (1.34 cm^3, 35.29 cm^3); p = 0.034). Steeper than average declines in grip strength between 53 and 69 were additionally weakly associated with an estimated 10% higher WMHV at age 69–71 (β = 1.10, 95% CI = (1.00, 1.22); p = 0.053). Conclusion This study provides preliminary evidence that tests of maximum grip strength may have value in predicting brain health. Future work should assess how these observed differences relate to later-life negative health outcomes, and whether changes in grip strength reflect concurrent changes in brain structure and connectivity.

scholarly journals Entorhinal cortex tau, amyloid-β, cortical thickness and memory performance in non-demented subjects

Brain ◽  
2019 ◽  
Vol 142 (4) ◽  
pp. 1148-1160 ◽  
Author(s):  
David S Knopman ◽  
Emily S Lundt ◽  
Terry M Therneau ◽  
Prashanthi Vemuri ◽  
Val J Lowe ◽  
...  
Keyword(s):  
Entorhinal Cortex ◽  
Cortical Thickness ◽  
Memory Performance ◽  
Verbal Learning ◽  
Amyloid Β ◽  
Gradient Boosting ◽  
Amyloid Pet ◽  
Delayed Recall ◽  
Age Related ◽  
Z Scores

AbstractAs more biomarkers for Alzheimer’s disease and age-related brain conditions become available, more sophisticated analytic approaches are needed to take full advantage of the information they convey. Most work has been done using categorical approaches but the joint relationships of tau PET, amyloid PET and cortical thickness in their continuous distributions to cognition have been under-explored. We evaluated non-demented subjects over age 50 years in the Mayo Clinic Study of Aging, 2037 of whom had undergone 3 T MRI scan, 985 amyloid PET scan with 11C-Pittsburgh compound B (PIB) and MRI, and 577 PIB-PET, 18F-AV1451 flortaucipir PET and MRI. Participants received a nine-test cognitive battery. Three test scores (logical memory delayed recall, visual reproduction delayed recall and auditory verbal learning test delayed recall) were used to generate a memory composite z-score. We used Gradient Boosting Machine models to analyse the relationship between regional cortical thickness, flortaucipir PET signal, PIB-PET signal and memory z-scores. Age, education, sex and number of test exposures were included in the model as covariates. In this population-based study of non-demented subjects, most of the associations between biomarkers and memory z-scores accrued after 70 years of age. Entorhinal cortex exhibited the strongest associations between biomarkers and memory z-scores. Other temporal regions showed similar but attenuated associations, and non-temporal regions had negligible associations between memory z-scores and biomarkers. Entorhinal flortaucipir PET signal, PIB-PET signal and entorhinal cortical thickness were independently and additively associated with declining memory z-scores. In contrast to global PIB-PET signal where only very high amyloid-β levels were associated low memory z-scores, entorhinal flortaucipir PET signal just above background levels was associated with low memory z-scores. The lowest memory z-scores occurred with the confluence of elevated entorhinal flortaucipir PET signal and lower entorhinal cortical thickness.

scholarly journals Brain structural differences between 73- and 92-year olds matched for childhood intelligence, social background, and intracranial volume

2017 ◽  
Author(s):  
Stuart J. Ritchie ◽  
David Alexander Dickie ◽  
Simon R. Cox ◽  
Maria del C. Valdés Hernández ◽  
Alison Pattie ◽  
...  
Keyword(s):  
White Matter ◽  
Cognitive Ability ◽  
Surface Area ◽  
Cortical Thickness ◽  
White Matter Hyperintensity ◽  
Socioeconomic Background ◽  
Intracranial Volume ◽  
Cortical Surface ◽  
Age Cohorts ◽  
Cortical Surface Area

AbstractFully characterizing age differences in the brain is a key task for combatting ageing-related cognitive decline. Using propensity score matching on two independent, narrow-age cohorts, we used data on childhood cognitive ability, socioeconomic background, and intracranial volume to match participants at mean age 92 years (n = 42) to very similar participants at mean age 73 (n = 126). Examining a variety of global and regional structural neuroimaging variables, there were large differences in grey and white matter volumes, cortical surface area, cortical thickness, and white matter hyperintensity volume and spatial extent. In a mediation analysis, the total volume of white matter hyperintensities and total cortical surface area jointly mediated 24.9% of the relation between age and general cognitive ability (tissue volumes and cortical thickness were not significant mediators in this analysis). These findings provide an unusual and valuable perspective on neurostructural ageing, in which brains from the eighth and tenth decades of life differ widely despite the same cognitive, socio-economic, and brain-volumetric starting points.

scholarly journals Grip strength from midlife as an indicator of later-life brain health and cognition: evidence from a British birth cohort

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Quentin Dercon ◽  
Jennifer M. Nicholas ◽  
Sarah-Naomi James ◽  
Jonathan M. Schott ◽  
Marcus Richards
Keyword(s):  
Grip Strength ◽  
Birth Cohort ◽  
Later Life ◽  
Cognitive Test ◽  
White Matter Hyperintensity ◽  
Brain Health ◽  
Time Points ◽  
Age Related ◽  
Maximum Grip Strength ◽  
Maximum Grip

Abstract Background Grip strength is an indicator of physical function with potential predictive value for health in ageing populations. We assessed whether trends in grip strength from midlife predicted later-life brain health and cognition. Methods 446 participants in an ongoing British birth cohort study, the National Survey of Health and Development (NSHD), had their maximum grip strength measured at ages 53, 60–64, and 69, and subsequently underwent neuroimaging as part of a neuroscience sub-study, referred to as “Insight 46”, at age 69–71. A group-based trajectory model identified latent groups of individuals in the whole NSHD cohort with below- or above-average grip strength over time, plus a reference group. Group assignment, plus standardised grip strength levels and change from midlife were each related to measures of whole-brain volume (WBV) and white matter hyperintensity volume (WMHV), plus several cognitive tests. Models were adjusted for sex, body size, head size (where appropriate), sociodemographics, and behavioural and vascular risk factors. Results Lower grip strength from midlife was associated with smaller WBV and lower matrix reasoning scores at age 69–71, with findings consistent between analysis of individual time points and analysis of trajectory groups. There was little evidence of an association between grip strength and other cognitive test scores. Although greater declines in grip strength showed a weak association with higher WMHV at age 69–71, trends in the opposite direction were seen at individual time points with higher grip strength at ages 60–64, and 69 associated with higher WMHV. Conclusions This study provides preliminary evidence that maximum grip strength may have value in predicting brain health. Future work should assess to what extent age-related declines in grip strength from midlife reflect concurrent changes in brain structure.

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.

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