Vitamin D and white matter abnormalities in older adults: A quantitative volumetric analysis of brain MRI

Background: Vitamin D insufficiency is associated with brain changes, and cognitive and mobility declines in older adults. Method: Two hundred and fifteen Caucasian older community-dwellers (mean±SD, 72.1±5.5years; 40% female) received a blood test and brain MRI. The thickness of perigenual anterior cingulate cortex, midcingulate cortex and posterior cingulate cortex was measured using FreeSurfer from T1-weighted MR images. Age, gender, education, BMI, mean arterial pressure, comorbidities, use of vitamin D supplements or anti-vascular drugs, MMSE, GDS, IADL, serum calcium and vitamin B9 concentrations, creatinine clearance were used as covariables. Results: Participants with vitamin D insufficiency (n=80) had thinner total cingulate thickness than the others (24.6±1.9mm versus 25.3±1.4mm, P=0.001); a significant difference found for all 3 regions. Vitamin D insufficiency was cross-sectionally associated with a decreased total cingulate thickness (β=- 0.49, P=0.028). Serum 25OHD concentration correlated positively with the thickness of perigenual anterior (P=0.011), midcingulate (P=0.013) and posterior cingulate cortex (P=0.021). Conclusion: Vitamin D insufficiency was associated with thinner cingulate cortex in the studied sample of older adults. These findings provide insight into the pathophysiology of cognitive and mobility declines in older adults with vitamin D insufficiency.

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Prospective associations between white matter hyperintensities and lower extremity function

Neurology ◽

10.1212/wnl.0000000000005289 ◽

2018 ◽

Vol 90 (15) ◽

pp. e1291-e1297 ◽

Cited By ~ 12

Author(s):

So Young Moon ◽

Philipe de Souto Barreto ◽

Yves Rolland ◽

Marie Chupin ◽

Ali Bouyahia ◽

...

Keyword(s):

Older Adults ◽

White Matter ◽

Lower Extremity ◽

White Matter Hyperintensities ◽

Brain Mri ◽

Community Dwelling ◽

Lower Extremity Function ◽

Mixed Effect ◽

Extremity Function ◽

Slow Progression

ObjectiveTo evaluate the relationship of white matter hyperintensities (WMH) with decline in lower extremity function (LEF) over approximately 3 years in dementia-free older adults with memory complaints.MethodsWe obtained brain MRI data from 458 community-dwelling adults, aged 70 years or over, at baseline, and from 358 adults over an average follow-up of 963 days. We evaluated LEF using the Short Physical Performance Battery (SPPB). We related baseline WMH volumes and progression to SPPB scores over time, using mixed-effect linear regressions. For the secondary analyses, we categorized baseline WMH volume into quartiles, and dichotomized the WMH progression to compare fast and slow progression.ResultsBaseline WMH volume (β = −0.017, 95% confidence interval [CI] −0.025 to −0.009), as well as WMH progression (β = −0.002, 95% CI −0.003 to −0.001), significantly associated with a decline in SPPB performance in adjusted analyses. Compared with the lowest quartile of baseline WMH volume, the highest quartile associated with a decline in SPPB performance (β = −0.301, 95% CI −0.558 to −0.044). Fast progression also associated with a decline in SPPB performance. We found clinically meaningful differences in the SPPB, with higher scores in participants with slow progression of WMH, at both 24 and 36 months.ConclusionsBaseline level and WMH progression associated with longitudinal decline in SPPB performance among older adults. We detected clinically meaningful differences in SPPB performance on comparing fast with slow progression of WMH, suggesting that speed of WMH progression is an important determinant of LEF during aging.

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Associations Between Frailty, Retinal Microvascular Changes, and Cerebral White Matter Abnormalities in Korean Older Adults

Journal of the American Geriatrics Society ◽

10.1111/jgs.13114 ◽

2014 ◽

Vol 62 (11) ◽

pp. 2209-2210 ◽

Cited By ~ 14

Author(s):

Hee-Won Jung ◽

Sun-Wook Kim ◽

Sol-Ji Yoon ◽

Jung-Yeon Choi ◽

Kwang-il Kim ◽

...

Keyword(s):

Older Adults ◽

White Matter ◽

Cerebral White Matter ◽

White Matter Abnormalities ◽

Microvascular Changes

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The 12-Word Philadelphia Verbal Learning Test Performances in Older Adults: Brain MRI and Cerebrospinal Fluid Correlates and Regression-Based Normative Data

Dementia and Geriatric Cognitive Disorders Extra ◽

10.1159/000494209 ◽

2018 ◽

Vol 8 (3) ◽

pp. 476-491 ◽

Cited By ~ 2

Author(s):

Katherine A. Gifford ◽

Dandan Liu ◽

Jacquelyn E. Neal ◽

Michelle A. Babicz ◽

Jennifer L. Thompson ◽

...

Keyword(s):

Older Adults ◽

Cerebrospinal Fluid ◽

White Matter ◽

Normative Data ◽

Verbal Learning ◽

Brain Mri ◽

Axonal Injury ◽

Cognitive Change ◽

Csf Biomarkers ◽

Learning Test

Background/Aims: This study evaluated neuroimaging and biological correlates, psychometric properties, and regression-based normative data of the 12-word Philadelphia Verbal Learning Test (PVLT), a list-learning test. Methods: Vanderbilt Memory and Aging Project participants free of clinical dementia and stroke (n = 230, aged 73 ± 7 years) completed a neuropsychological protocol and brain MRI. A subset (n = 111) underwent lumbar puncture for analysis of Alzheimer’s disease (AD) and axonal integrity cerebrospinal fluid (CSF) biomarkers. Regression models related PVLT indices to MRI and CSF biomarkers adjusting for age, sex, race/ethnicity, education, APOE-ε4 carrier status, cognitive status, and intracranial volume (MRI models). Secondary analyses were restricted to participants with normal cognition (NC; n = 127), from which regression-based normative data were generated. Results: Lower PVLT performances were associated with smaller medial temporal lobe volumes (p < 0.05) and higher CSF tau concentrations (p < 0.04). Among NC, PVLT indices were associated with white matter hyperintensities on MRI and an axonal injury biomarker (CSF neurofilament light; p < 0.03). Conclusion: The PVLT appears sensitive to markers of neurodegeneration, including temporal regions affected by AD. Conversely, in cognitively normal older adults, PVLT performance seems to relate to white matter disease and axonal injury, perhaps reflecting non-AD pathways to cognitive change. Enhanced normative data enrich the clinical utility of this tool.

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Systematic volumetric analysis predicts response to CSF drainage and outcome to shunt surgery in idiopathic normal pressure hydrocephalus

European Radiology ◽

10.1007/s00330-020-07531-z ◽

2021 ◽

Author(s):

Dan Wu ◽

Abhay Moghekar ◽

Wen Shi ◽

Ari M. Blitz ◽

Susumu Mori

Keyword(s):

White Matter ◽

Normal Pressure Hydrocephalus ◽

Neurodegenerative Disorder ◽

Brain Mri ◽

Area Under The Curve ◽

Normal Pressure ◽

Volumetric Analysis ◽

Idiopathic Normal Pressure Hydrocephalus ◽

Shunt Placement ◽

Csf Drainage

Abstract Objectives Idiopathic normal pressure hydrocephalus (INPH) is a neurodegenerative disorder characterized by excess cerebrospinal fluid (CSF) in the ventricles, which can be diagnosed by invasive CSF drainage test and treated by shunt placement. Here, we aim to investigate the diagnostic and prognostic power of systematic volumetric analysis based on brain structural MRI for INPH. Methods We performed a retrospective study with a cohort of 104 probable INPH patients who underwent CSF drainage tests and another cohort of 41 INPH patients who had shunt placement. High-resolution T1-weighted images of the patients were segmented using an automated pipeline into 283 structures that are grouped into different granularity levels for volumetric analysis. Volumes at multi-granularity levels were used in a recursive feature elimination model to classify CSF drainage responders and non-responders. We then used pre-surgical brain volumes to predict Tinetti and MMSE scores after shunting, based on the least absolute shrinkage and selection operator. Results The classification accuracy of differentiating the CSF drainage responders and non-responders increased as the granularity increased. The highest diagnostic accuracy was achieved at the finest segmentation with a sensitivity/specificity/precision/accuracy of 0.89/0.91/0.84/0.90 and an area under the curve of 0.94. The predicted post-surgical neurological scores showed high correlations with the ground truth, with r = 0.80 for Tinetti and r = 0.88 for MMSE. The anatomical features that played important roles in the diagnostic and prognostic tasks were also illustrated. Conclusions We demonstrated that volumetric analysis with fine segmentation could reliably differentiate CSF drainage responders from other INPH-like patients, and it could accurately predict the neurological outcomes after shunting. Key Points • We performed a fully automated segmentation of brain MRI at multiple granularity levels for systematic volumetric analysis of idiopathic normal pressure hydrocephalus (INPH) patients. • We were able to differentiate patients that responded to CSF drainage test with an accuracy of 0.90 and area under the curve of 0.94 in a cohort of 104 probable INPH patients, as well as to predict the post-shunt gait and cognitive scores with a coefficient of 0.80 for Tinetti and 0.88 for MMSE. • Feature analysis showed the inferior lateral ventricle, bilateral hippocampus, and orbital cortex are positive indicators of CSF drainage responders, whereas the posterior deep white matter and parietal subcortical white matter were negative predictors.

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Brain White Matter Structure and Amyloid Deposition in Black and White Older Adults: The ARIC‐PET Study

Journal of the American Heart Association ◽

10.1161/jaha.121.022087 ◽

2021 ◽

Author(s):

Keenan A. Walker ◽

Noah Silverstein ◽

Yun Zhou ◽

Timothy M. Hughes ◽

Clifford R. Jack ◽

...

Keyword(s):

Older Adults ◽

Positron Emission Tomography ◽

White Matter ◽

Community Sample ◽

Amyloid Deposition ◽

Emission Tomography ◽

White Matter Hyperintensity ◽

White Matter Abnormalities ◽

Brain White Matter ◽

Positron Emission

Background White matter abnormalities are a common feature of aging and Alzheimer disease, and tend to be more severe among Black individuals. However, the extent to which white matter abnormalities relate to amyloid deposition, a marker of Alzheimer pathology, remains unclear. This cross‐sectional study examined the association of white matter abnormalities with cortical amyloid in a community sample of older adults without dementia and examined the moderating effect of race. Methods and Results Participants from the ARIC‐PET (Atherosclerosis Risk in Communities‐Positron Emission Tomography) study underwent brain magnetic resonance imaging, which quantified white matter hyperintensity volume and microstructural integrity using diffusion tensor imaging. Participants received florbetapir positron emission tomography imaging to measure brain amyloid. Associations between measures of white matter structure and elevated amyloid status were examined using multivariable logistic regression. Among 322 participants (43% Black), each SD increase in white matter hyperintensity volume was associated with a greater odds of elevated amyloid (odds ratio [OR], 1.37; 95% CI, 1.03–1.83) after adjusting for demographic and cardiovascular risk factors. In race‐stratified analyses, a greater white matter hyperintensity volume was more strongly associated with elevated amyloid among Black participants (OR, 2.00; 95% CI, 1.15–3.50), compared with White participants (OR, 1.29; 95% CI, 0.89–1.89). However, the race interaction was not statistically significant ( P interaction=0.09). We found no association between white matter microstructure and elevated amyloid. Conclusions The results suggest a modest positive relationship between white matter hyperintensity and elevated amyloid in older adults without dementia. Although the results indicate that this association is nonsignificantly stronger among Black participants, these findings will need to be confirmed or refuted using larger multiracial cohorts.

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The association of brain structure with gait velocity in older adults: a quantitative volumetric analysis of brain MRI

Neuroradiology ◽

10.1007/s00234-015-1536-2 ◽

2015 ◽

Vol 57 (8) ◽

pp. 851-861 ◽

Cited By ~ 27

Author(s):

Ali Ezzati ◽

Mindy J. Katz ◽

Michael L. Lipton ◽

Richard B. Lipton ◽

Joe Verghese

Keyword(s):

Older Adults ◽

Brain Structure ◽

Brain Mri ◽

Volumetric Analysis ◽

Gait Velocity

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REDUCED ENDOTHELIAL FUNCTION IS ASSOCIATED WITH DEEP WHITE MATTER LESION VOLUMES AMONG HEALTHY OLDER ADULTS

Innovation in Aging ◽

10.1093/geroni/igz038.160 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

pp. S41-S41

Author(s):

Regina S Wright ◽

Desiree Bygrave

Keyword(s):

Older Adults ◽

White Matter ◽

Endothelial Function ◽

White Matter Lesion ◽

Brain Mri ◽

Brain Magnetic Resonance Imaging ◽

Regions Of Interest ◽

Outcome Variable ◽

Inverse Association ◽

Healthy Older Adults

Abstract Reduced endothelial function (EF) is a subclinical cardiovascular disease (CVD) risk factor and precursor to hypertension and atherosclerosis. Among older adults with CVD, reduced EF has been associated with poorer outcomes in a number of cognitive domains, partly explained by the presence of white matter lesion volumes (WMLV) detectable on brain magnetic resonance imaging (MRI). The role of EF as a key, early predictor of brain decrements among older adults without CVD, however, is not well understood. Therefore, the objective of the study was to examine associations between endothelial function and WMLV among cognitively intact older adults free of CVD. A diverse sample of 138 community-based older adults (30.4% male; mean age=68.54y) enrolled in the Healthy Heart & Mind Study underwent cognitive and psychosocial assessment, vascular testing, and brain MRI. Multiple regressions were run to examine associations between endothelial function, as measured by % change in brachial artery flow-mediated dilation (FMD), and MRI-assessed WMLV in brain regions of interest, after controlling for age, sex, race, education, depression, mean arterial pressure, total cholesterol, and hypertension medication use. Results showed a significant inverse association between % FMD change and deep WMLV (p<.05), but no other regions of interest. Results suggest that reduced EF is associated with greater deep WMLV, an outcome variable attributable to small vessel disease and linked to Alzheimer’s disease in previous studies. The implications of this finding for predicting risk for cognitive impairment among healthy older adults will be discussed.

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Brain pathology is related to total daily physical activity in older adults

Neurology ◽

10.1212/wnl.0000000000005552 ◽

2018 ◽

Vol 90 (21) ◽

pp. e1911-e1919 ◽

Cited By ~ 9

Author(s):

Aron S. Buchman ◽

Robert J. Dawe ◽

Lei Yu ◽

Andrew Lim ◽

Robert S. Wilson ◽

...

Keyword(s):

Physical Activity ◽

Older Adults ◽

White Matter ◽

Daily Activity ◽

Brain Mri ◽

Neuronal Loss ◽

Daily Physical Activity ◽

Postmortem Brain ◽

Amyloid Angiopathy ◽

Brain Pathology

ObjectiveTo test the hypothesis that brain pathology is associated with total daily physical activity proximate to death in older adults.MethodsWe studied brain autopsies from 428 decedents of the Rush Memory and Aging Project. The quantity of all physical activity was measured continuously for up to 10 days with actigraphy (Actical; Philips Healthcare, Bend, OR). Multiple regression analyses controlling for age and sex were used to examine the relation of brain indexes to total daily physical activity and other clinical covariates proximate to death.ResultsAverage total daily activity was 1.53 × 105 counts/d (SD 1.14 × 105 counts/d), and mean age at death was 90.6 (SD 6.12) years. Nigral neuronal loss (estimate −0.232, standard error [SE] = 0.070, p = 0.001) and macroinfarcts (estimate −0.266, SE 0.112, p = 0.017) were independently associated with total daily physical activity proximate to death, accounting for an additional 2.4% of the variance of total daily activity. Other postmortem indexes (Alzheimer disease, Lewy bodies, TAR DNA-binding protein 43, hippocampal sclerosis, microinfarcts, atherosclerosis, arteriolosclerosis, and cerebral amyloid angiopathy) were not associated with total daily activity. In 295 cases (70%), we derived a measure of white matter tissue integrity from postmortem brain MRI. This metric accounted for an additional 5.8% of the variance of total daily physical activity when controlling for age, sex, nigral neuronal loss, and macroinfarcts.ConclusionMacroinfarcts, nigral neuronal loss, and white matter pathologies are related to total daily physical activity in older adults, but further studies are needed to explain its pathologic basis more fully.

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