Microstructural Neuroimaging of Frailty in Cognitively Normal Older Adults

Abstract Physical frailty is an age-related clinical syndrome that is related to adverse health outcomes, including cognitive impairment and dementia. Recent studies have shown structural neuroimaging correlates with frailty. However, most existing evidence relies on brain volumetric measures. Whether brain microstructure is associated with frailty and its spatial distribution have not been explored. In the Baltimore Longitudinal Study of Aging, we identified 776 cognitively normal participants aged 50 and older who had concurrent data on frailty and brain microstructure by diffusion tensor imaging (DTI), including mean diffusivity (MD) of gray matter and fractional anisotropy (FA) of white matter. We first identified neuroimaging markers that were associated with frailty score (0-5) and further examined their relationships with frailty status (0: non-frail, 1-2: pre-frail, 3+: frail) using multivariate linear regression. Models were adjusted for age, sex, race, years of education, and Apolipoprotein E e4 carrier status. DTI-based neuroimaging markers that were associated with frailty status were localized in the supplementary motor area of the frontal lobe, several subcortical regions (putamen, caudate), and body and splenium of corpus callosum. This study demonstrates for the first time that microstructure of both gray and white matter differs by frailty levels in cognitively normal older adults. Brain areas were not widespread, but mostly localized in gray matter subcortical motor areas and white matter corpus callosum. Whether changes in brain microstructure precede future frailty development warrants further investigation.

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Loss of white matter integrity reflects tau accumulation in Alzheimer disease defined regions

Neurology ◽

10.1212/wnl.0000000000005864 ◽

2018 ◽

Vol 91 (4) ◽

pp. e313-e318 ◽

Cited By ~ 23

Author(s):

Jeremy F. Strain ◽

Robert X. Smith ◽

Helen Beaumont ◽

Catherine M. Roe ◽

Brian A. Gordon ◽

...

Keyword(s):

White Matter ◽

Alzheimer Disease ◽

Gray Matter ◽

Structural Integrity ◽

Diffusion Tensor ◽

Mean Diffusivity ◽

Cognitively Impaired ◽

Cognitively Normal ◽

Advanced Stages ◽

Amyloid Aβ

ObjectiveWhite matter (WM) projections were assessed from Alzheimer disease (AD) gray matter regions associated with β-amyloid (Aβ), tau, or neurodegeneration to ascertain relationship between WM structural integrity with Aβ and/or tau deposition.MethodsParticipants underwent diffusion tensor imaging (DTI), PET Aβ ([18F]AV-45 [florbetapir]), and PET tau ([18F]AV-1451 [flortaucipir]) imaging. Probabilistic WM summary and individual tracts were created from either a composite or individual gray matter seed regions derived from Aβ, tau, and neurodegeneration. Linear regressions were performed for Aβ, age, tau and WM hyperintensities (WMH) to predict mean diffusivity (MD) or fractional anisotropy (FA) from the corresponding WM summaries or tracts.ResultsOur cohort was composed of 59 cognitively normal participants and 10 cognitively impaired individuals. Aβ was not associated with DTI metrics in WM summary or individual tracts. Age and WMH strongly predicted MD and FA in several WM regions, with tau a significant predictor of MD only in the anterior temporal WM.ConclusionTau, not Aβ, was associated with changes in anterior temporal WM integrity. WMH, a proxy for vascular damage, was strongly associated with axonal damage, but tau independently contributed to the model, suggesting an additional degenerative mechanism within tracts projecting from regions vulnerable to AD pathology. WM decline was associated with early tau accumulation, and further decline may reflect tau propagation in more advanced stages of AD.

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White matter abnormalities in the corpus callosum with cognitive impairment in Parkinson disease

Neurology ◽

10.1212/wnl.0000000000006646 ◽

2018 ◽

Vol 91 (24) ◽

pp. e2244-e2255 ◽

Cited By ~ 16

Author(s):

Ian O. Bledsoe ◽

Glenn T. Stebbins ◽

Doug Merkitch ◽

Jennifer G. Goldman

Keyword(s):

Cognitive Impairment ◽

White Matter ◽

Corpus Callosum ◽

Parkinson Disease ◽

Information Transfer ◽

Diffusion Tensor ◽

Anterior Segment ◽

Mean Diffusivity ◽

Cognitive Domain ◽

White Matter Abnormalities

ObjectiveTo evaluate microstructural characteristics of the corpus callosum using diffusion tensor imaging (DTI) and their relationships to cognitive impairment in Parkinson disease (PD).MethodsSeventy-five participants with PD and 24 healthy control (HC) participants underwent structural MRI brain scans including DTI sequences and clinical and neuropsychological evaluations. Using Movement Disorder Society criteria, PD participants were classified as having normal cognition (PD-NC, n = 23), mild cognitive impairment (PD-MCI, n = 35), or dementia (PDD, n = 17). Cognitive domain (attention/working memory, executive function, language, memory, visuospatial function) z scores were calculated. DTI scalar values, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD), were established for 5 callosal segments on a midsagittal plane, single slice using a topographically derived parcellation method. Scalar values were compared among participant groups. Regression analyses were performed on cognitive domain z scores and DTI metrics.ResultsParticipants with PD showed increased AD values in the anterior 3 callosal segments compared to healthy controls. Participants with PDD had significantly increased AD, MD, and RD in the anterior 2 segments compared to participants with PD-NC and most anterior segment compared to participants with PD-MCI. FA values did not differ significantly between participants with PD and participants with HC or among PD cognitive groups. The strongest associations for the DTI metrics and cognitive performance occurred in the most anterior and most posterior callosal segments, and also reflected fronto-striatal and posterior cortical type cognitive deficits, respectively.ConclusionsMicrostructural white matter abnormalities of the corpus callosum, as measured by DTI, may contribute to PD cognitive impairment by disrupting information transfer across interhemispheric and callosal–cortical projections.

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Tract Specificity of Age Effects on Diffusion Tensor Imaging Measures of White Matter Health

Frontiers in Aging Neuroscience ◽

10.3389/fnagi.2021.628865 ◽

2021 ◽

Vol 13 ◽

Author(s):

Stephanie Matijevic ◽

Lee Ryan

Keyword(s):

Older Adults ◽

Diffusion Tensor Imaging ◽

Individual Differences ◽

White Matter ◽

Diffusion Tensor ◽

Mean Diffusivity ◽

White Matter Integrity ◽

White Matter Tracts ◽

Apoe Ε4 ◽

Age Related

Well-established literature indicates that older adults have poorer cerebral white matter integrity, as measured through diffusion tensor imaging (DTI). Age differences in DTI have been observed widely across white matter, although some tracts appear more sensitive to the effects of aging than others. Factors like APOE ε4 status and sex may contribute to individual differences in white matter integrity that also selectively impact certain tracts, and could influence DTI changes in aging. The present study explored the degree to which age, APOE ε4, and sex exerted global vs. tract specific effects on DTI metrics in cognitively healthy late middle-aged to older adults. Data from 49 older adults (ages 54–92) at two time-points separated by approximately 2.7 years were collected. DTI metrics, including fractional anisotropy (FA) and mean diffusivity (MD), were extracted from nine white matter tracts and global white matter. Results showed that across timepoints, FA and MD increased globally, with no tract-specific changes observed. Baseline age had a global influence on both measures, with increasing age associated with lower FA and higher MD. After controlling for global white matter FA, age additionally predicted FA for the genu, callosum body, inferior fronto-occipital fasciculus (IFOF), and both anterior and posterior cingulum. Females exhibited lower global FA on average compared to males. In contrast, MD was selectively elevated in the anterior cingulum and superior longitudinal fasciculus (SLF), for females compared to males. APOE ε4 status was not predictive of either measure. In summary, these results indicate that age and sex are associated with both global and tract-specific alterations to DTI metrics among a healthy older adult cohort. Older women have poorer white matter integrity compared to older men, perhaps related to menopause-induced metabolic changes. While age-related alterations to white matter integrity are global, there is substantial variation in the degree to which tracts are impacted, possibly as a consequence of tract anatomical variability. The present study highlights the importance of accounting for global sources of variation in DTI metrics when attempting to investigate individual differences (due to age, sex, or other factors) in specific white matter tracts.

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Corpus Callosum and Cingulum Tractography in Parkinson's Disease

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100010751 ◽

2010 ◽

Vol 37 (5) ◽

pp. 595-600 ◽

Cited By ~ 28

Author(s):

Katie Wiltshire ◽

Luis Concha ◽

Myrlene Gee ◽

Thomas Bouchard ◽

Christian Beaulieu ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cognitive Impairment ◽

White Matter ◽

Corpus Callosum ◽

Diffusion Tensor ◽

Mean Diffusivity ◽

Imaging Method ◽

Motor Symptoms ◽

Mri Scans

Background:In Parkinson's disease (PD) cell loss in the substantia nigra is known to result in motor symptoms; however widespread pathological changes occur and may be associated with non-motor symptoms such as cognitive impairment. Diffusion tensor imaging is a quantitative imaging method sensitive to the micro-structure of white matter tracts.Objective:To measure fractional anisotropy (FA) and mean diffusivity (MD) values in the corpus callosum and cingulum pathways, defined by diffusion tensor tractography, in patients with PD, PD with dementia (PDD) and controls and to determine if these measures correlate with Mini-Mental Status Examination (MMSE) scores in parkinsonian patients.Methods:Patients with PD (17 Males [M], 12 Females [F]), mild PDD (5 M, 1F) and controls (8 M, 7F) underwent cognitive testing and MRI scans. The corpus callosum was divided into four regions and the cingulum into two regions bilaterally to define tracts using the program DTIstudio (Johns Hopkins University) using the fiber assignment by continuous tracking algorithm. Volumetric MRI scans were used to measure white and gray matter volumes.Results:Groups did not differ in age or education. There were no overall FA or MD differences between groups in either the corpus callosum or cingulum pathways. In PD subjects the MMSE score correlated with MD within the corpus callosum. These findings were independent of age, sex and total white matter volume.Conclusions:The data suggest that the corpus callosum or its cortical connections are associated with cognitive impairment in PD patients.

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Hyposmia and Neuroimaging Signature in Community-Dwelling Older Adults

Innovation in Aging ◽

10.1093/geroni/igaa057.1709 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

pp. 530-530

Author(s):

Cynthia Felix ◽

Lana Chahine ◽

Honglei Chen ◽

Zichun Cao ◽

Caterina Rosano

Keyword(s):

Older Adults ◽

Gray Matter ◽

Orbitofrontal Cortex ◽

Diffusion Tensor ◽

Mean Diffusivity ◽

Community Dwelling ◽

Intracranial Volume ◽

Total Brain ◽

Identification Test ◽

Community Dwelling Older Adults

Abstract Olfaction declines with aging, and hyposmia, or impaired sense of smell, is associated with neurodegenerative disorders including Alzheimer’s Disease (AD) and Parkinson’s Disease (PD). Neuroimaging studies of hyposmia in AD/PD patients have often examined pathology-specific brain regions. Our knowledge of neural correlates in regions that mediate olfaction in community-dwelling older adults, is limited. We quantified mean diffusivity (MD) of the gray matter (GM) using diffusion tensor imaging in a community-dwelling sample of 308 older adults (mean age: 82.9 years, 58% women, 40% black). We focused on total brain and these regions involved in olfaction- olfactory bulb, amygdala, entorhinal cortex, orbitofrontal cortex, and hippocampus. Smell was tested with a scratch-and-sniff validated odor identification test, the Brief Smell Identification Test (BSIT). Hyposmia was defined as BSIT score of ≤8, assessed about 7 years prior to neuroimaging. In our sample, 23% had hyposmia, more in in men (30%) than in women (19%). Hyposmia was not significantly associated with cardiovascular risk factors such as hypertension; diseases such as stroke; age; race; cognitive or mobility functions (all p>0.1). In linear regression models adjusted for demographics and brain atrophy (total brain gray matter volume divided by intracranial volume), hyposmia was significantly associated with higher GM MD (lower microstructural integrity) of the left orbitofrontal cortex (standardized beta: 0.142, t=2.56, p=0.011). Understanding the neural substrates involved in hyposmia in aging is an important step towards advancing research on hyposmia in non-clinic-based, community-dwelling populations.

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6-month aerobic walking training increases T1w/T2w signal in the white matter of healthy older adults

10.1101/2020.11.09.20228627 ◽

2020 ◽

Author(s):

Andrea Mendez Colmenares ◽

Michelle W Voss ◽

Jason Fanning ◽

Elizabeth A Salerno ◽

Neha P Gothe ◽

...

Keyword(s):

Older Adults ◽

White Matter ◽

Corpus Callosum ◽

Aerobic Exercise ◽

Active Control ◽

Diffusion Tensor ◽

Positive Change ◽

Control Group ◽

Healthy Older Adults ◽

Exercise Interventions

AbstractWhite matter (WM) deterioration is an important mechanism of cognitive decline in healthy aging and dementia. Engaging in aerobic exercise to improve cardiorespiratory fitness (CRF) is considered one of the most promising ways to improve cognitive and brain health in aging. Yet, no randomized controlled trials have reported benefits of aerobic exercise interventions on WM microstructure measured with diffusion tensor imaging. Here, we studied the effects of a 6-month exercise intervention (clinical trial NCT01472744) on WM of 180 cognitively healthy older adults (60–79 years) using the ratio of calibrated T1-weighted image to T2-weighted images (T1w/T2w). Participants were randomized to one of four groups including a low intensity activity with complex cognitive demands (Dance), Walking, Walking + nutritional supplement or an active control. Results showed that a 6-month aerobic walking and dance intervention produced positive changes in the T1w/T2w with significant time-by-group interactions in the total WM, the genu and splenium of the corpus callosum, forceps minor, cingulum, relative to an active control condition. In contrast, we observed a decline in T1w/T2w in the majority of WM regions in the active control group. Lastly, a positive change in the T1w/T2w in the genu of the corpus callosum correlated with a positive change in episodic memory in the Walking but not in the control group; however, there were no associations between change in the T1w/T2w and change in CRF. Together, our findings suggest that the T1w/T2w may be a sensitive metric to detect short-term within-person changes in the WM and intervention-induced WM plasticity in the adult human brain.

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Deep medullary veins are associated with widespread brain structural abnormalities

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x211065210 ◽

2021 ◽

pp. 0271678X2110652

Author(s):

Zi-Yue Liu ◽

Fei-Fei Zhai ◽

Dong-Hui Ao ◽

Fei Han ◽

Ming-Li Li ◽

...

Keyword(s):

White Matter ◽

Gray Matter ◽

Diffusion Tensor ◽

Mean Diffusivity ◽

Cortical Atrophy ◽

Intracranial Volume ◽

Brain Parenchymal ◽

Occipital Lobes ◽

Microstructural Integrity ◽

Deep Medullary Veins

Our aim is to investigate the association of cerebral deep medullary veins (DMVs) with white matter microstructural integrity and regional brain atrophy in MRI. In a community-based cohort of 979 participants (mean age 55.4 years), DMVs were identified on susceptibility-weighted imaging. Brain structural measurements including gray matter and hippocampus volumes, as well as diffusion tensor metrics, were evaluated. The mean (SD)number of DMVs was 19.0 (1.7). A fewer number of DMVs was related to lower fractional anisotropy and higher mean diffusivity in multiple voxels on the white matter skeleton (threshold-free cluster enhancement corrected p < 0.05, adjusted for age and sex). Also, fewer DMVs were significantly related to a lower gray matter fraction and a hippocampal fraction (0.10 and 0.11 per DMV, respectively; SE, 0.03 for both; p < 0.001 for both). A significant correlation between DMVs’ reduction and cortical atrophy was observed in the bilateral occipital lobes, temporal lobes, hippocampus, and frontal lobes (p < 0.001, adjusted for age, sex, and total intracranial volume). Our results provided evidence that cerebral small venules disease play a role in brain parenchymal lesions and neurodegenerative processes.

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Diffusion Tensor Imaging: A Promising New Technique for Accurate Identification of the Stria Medullaris and Habenula

The Open Neuroimaging Journal ◽

10.2174/1874440002114010001 ◽

2021 ◽

Vol 14 (1) ◽

pp. 1-7

Author(s):

Osama Kheiralla ◽

Aymen Abdalkariem ◽

Ali Alghamdi ◽

Abdulrahman Tajaldeen ◽

Naif Hamid

Keyword(s):

Diffusion Tensor Imaging ◽

White Matter ◽

Diffusion Tensor ◽

Mean Diffusivity ◽

Imaging Method ◽

Accurate Identification ◽

White Matter Tracts ◽

Brain Microstructure ◽

Primary Output

The Stria Medullaris (SM) is a white-matter tract that contains afferent fibres that connect the cognitive-emotional areas in the forebrain to the Habenula (Hb). The Hb plays an important role in behavioral responses to reward, stress, anxiety, pain, and sleep through its action on neuromodulator systems. The Fasciculus Retroflexus (FR) forms the primary output of the Hb to the midbrain. The SM, Hb, and FR are part of a special pathway between the forebrain and the midbrain known as the Dorsal Diencephalic Conduction system (DDC). Hb dysfunction is accompanied by different types of neuropsychiatric disorders, such as schizophrenia, depression, and Treatment-Resistant Depression (TRD). Due to difficulties in the imaging assessment of the SM and HB in vivo, they had not been a focus of clinical studies until the invention of Diffusion Tensor Imaging (DTI), which has revolutionized the imaging and investigation of the SM and Hb. DTI has facilitated the imaging of the SM and Hb and has provided insights into their properties through the investigation of their monoamine dysregulation. DTI is a well-established technique for mapping brain microstructure and white matter tracts; it provides indirect information about the microstructural architecture and integrity of white matter in vivo, based on water diffusion properties in the intra- and extracellular space, such as Axial Diffusivity (AD), Radial Diffusivity (RD), mean diffusivity, and Fractional Anisotropy (FA). Neurosurgeons have recognized the potential value of DTI in the direct anatomical targeting of the SM and Hb prior to Deep Brain Stimulation (DBS) surgery for the treatment of certain neuropsychiatric conditions, such as TRD. DTI is the only non-invasive method that offers the possibility of visualization in vivo of the white-matter tracts and nuclei in the human brain. This review study summarizes the use of DTI as a promising new imaging method for accurate identification of the SM and Hb, with special emphasis on direct anatomical targeting of the SM and Hb prior to DBS surgery.

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Diffusion tensor imaging in hyperthyroidism: assessment of microstructural white matter abnormality with a tract-based spatial statistical analysis

Acta Radiologica ◽

10.1177/0284185120909960 ◽

2020 ◽

Vol 61 (12) ◽

pp. 1677-1683 ◽

Cited By ~ 1

Author(s):

Kerim Aslan ◽

Hediye Pinar Gunbey ◽

Sumeyra Cortcu ◽

Onur Ozyurt ◽

Ugur Avci ◽

...

Keyword(s):

Diffusion Tensor Imaging ◽

White Matter ◽

Corpus Callosum ◽

Diffusion Tensor ◽

Mean Diffusivity ◽

Imaging Study ◽

Internal Capsule ◽

Control Group ◽

Corona Radiata ◽

Microstructural Alterations

Background Metabolic, morphological, and functional brain changes associated with a neurological deficit in hyperthyroidism have been observed. However, changes in microstructural white matter (WM), which can explain the underlying pathophysiology of brain dysfunctions, have not been researched. Purpose To assess microstructural WM abnormality in patients with untreated or newly diagnosed hyperthyroidism using tract-based spatial statistics (TBSS). Material and Methods Eighteen patients with hyperthyroidism and 14 age- and sex-matched healthy controls were included in this study. TBSS were used in this diffusion tensor imaging study for a whole-brain voxel-wise analysis of fractional anisotropy, mean diffusivity, axial diffusivity (AD), and radial diffusivity (RD) of WM. Results When compared to the control group, TBSS showed a significant increase in the RD of the corpus callosum, anterior and posterior corona radiata, posterior thalamic radiation, cingulum, superior longitudinal fasciculus, and the retrolenticular region of the internal capsule in patients with hyperthyroidism ( P < 0.05), as well as a significant decrease in AD in the anterior corona radiata and the genu of corpus callosum ( P < 0.05). Conclusion This study showed that more regions are affected by the RD increase than the AD decrease in the WM tracts of patients with hyperthyroidism. These preliminary results suggest that demyelination is the main mechanism of microstructural alterations in the WM of hyperthyroid patients.

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Rest-activity rhythms and white matter microstructure across the lifespan

SLEEP ◽

10.1093/sleep/zsaa266 ◽

2020 ◽

Author(s):

Megan McMahon ◽

Yoshita Malneedi ◽

Darrell A Worthy ◽

David M Schnyer

Keyword(s):

Older Adults ◽

White Matter ◽

Adult Development ◽

Diffusion Tensor ◽

Mean Diffusivity ◽

Brain White Matter ◽

White Matter Microstructure ◽

Sleep Physiology ◽

Rhythm Stability ◽

Rest Activity

Abstract Study Objectives The purpose of this study was to examine how rest-activity (RA) rhythm stability may be associated with white matter microstructure across the lifespan in healthy adults free of significant cardiovascular risk. Methods We analyzed multi-shell diffusion tensor images from 103 healthy young and older adults using tract-based spatial statistics (TBSS) to examine relationships between white matter microstructure and RA rhythm stability. RA measures were computed using both cosinor and non-parametric methods derived from 7 days of actigraphy data. Fractional anisotropy (FA) and mean diffusivity (MD) were examined in this analysis. Because prior studies have suggested that the corpus callosum (CC) is sensitive to sleep physiology and RA rhythms, we also conducted a focused region of interest analysis on the CC. Results Greater rest-activity rhythm stability was associated with greater FA across both young and older adults, primarily in the CC and anterior corona radiata. This effect was not moderated by age group. While RA measures were associated with sleep metrics, RA rhythm measures uniquely accounted for the variance in white matter integrity. Conclusions This study strengthens existing evidence for a relationship between brain white matter structure and RA rhythm stability in the absence of health risk factors. While there are differences in RA stability between age groups, the relationship with brain white matter was present across both young and older adults. RA rhythms may be a useful biomarker of brain health across both periods of adult development.

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