Melissa Lamar

YNICL Journal 2021 Journal Article

ARTS: A novel In-vivo classifier of arteriolosclerosis for the older adult brain

• Nazanin Makkinejad
• Arnold M. Evia
• Ashish A. Tamhane
• Carles Javierre-Petit
• Sue E. Leurgans
• Melissa Lamar
• Lisa L. Barnes
• David A. Bennett

Brain arteriolosclerosis, one of the main pathologies of cerebral small vessel disease, is common in older adults and has been linked to lower cognitive and motor function and higher odds of dementia. In spite of its frequency and associated morbidity, arteriolosclerosis can only be diagnosed at autopsy. Therefore, the purpose of this work was to develop an in-vivo classifier of arteriolosclerosis based on brain MRI. First, an ex-vivo classifier of arteriolosclerosis was developed based on features related to white matter hyperintensities, diffusion anisotropy and demographics by applying machine learning to ex-vivo MRI and pathology data from 119 participants of the Rush Memory and Aging Project (MAP) and Religious Orders Study (ROS), two longitudinal cohort studies of aging that recruit non-demented older adults. The ex-vivo classifier showed good performance in predicting the presence of arteriolosclerosis, with an average area under the receiver operating characteristic curve AUC = 0.78. The ex-vivo classifier was then translated to in-vivo based on available in-vivo and ex-vivo MRI data on the same participants. The in-vivo classifier was named ARTS (short for ARTerioloSclerosis), is fully automated, and provides a score linked to the likelihood a person suffers from arteriolosclerosis. The performance of ARTS in predicting the presence of arteriolosclerosis in-vivo was tested in a separate, 91% dementia-free group of 79 MAP/ROS participants and exhibited an AUC = 0.79 in persons with antemortem intervals shorter than 2.4 years. This level of performance in mostly non-demented older adults is notable considering that arteriolosclerosis can only be diagnosed at autopsy. The scan-rescan reproducibility of the ARTS score was excellent, with an intraclass correlation of 0.99, suggesting that application of ARTS in longitudinal studies may show high sensitivity in detecting small changes. Finally, higher ARTS scores in non-demented older adults were associated with greater decline in cognition two years after baseline MRI, especially in perceptual speed which has been linked to arteriolosclerosis and small vessel disease. This finding was shown in a separate group of 369 non-demented MAP/ROS participants and was validated in 72 non-demented Black participants of the Minority Aging Research Study (MARS) and also in 244 non-demented participants of the Alzheimer's Disease Neuroimaging Initiative 2 and 3. The results of this work suggest that ARTS may have broad implications in the advancement of diagnosis, prevention and treatment of arteriolosclerosis. ARTS is publicly available at https://www.nitrc.org/projects/arts/.

YNIMG Journal 2019 Journal Article

Cardiovascular disease risk factors, tract-based structural connectomics, and cognition in older adults

• Elizabeth A. Boots
• Liang Zhan
• Catherine Dion
• Aimee J. Karstens
• Jamie C. Peven
• Olusola Ajilore
• Melissa Lamar

Cardiovascular disease risk factors (CVD-RFs) are associated with decreased gray and white matter integrity and cognitive impairment in older adults. Less is known regarding the interplay between CVD-RFs, brain structural connectome integrity, and cognition. We examined whether CVD-RFs were associated with measures of tract-based structural connectivity in 94 non-demented/non-depressed older adults and if alterations in connectivity mediated associations between CVD-RFs and cognition. Participants (age = 68. 2 years; 52. 1% female; 46. 8% Black) underwent CVD-RF assessment, MRI, and cognitive evaluation. Framingham 10-year stroke risk (FSRP-10) quantified CVD-RFs. Graph theory analysis integrated T1-derived gray matter regions of interest (ROIs; 23 a-priori ROIs associated with CVD-RFs and dementia), and diffusion MRI-derived white matter tractography into connectivity matrices analyzed for local efficiency and nodal strength. A principal component analysis resulted in three rotated factor scores reflecting executive function (EF; FAS, Trail Making Test (TMT) B-A, Letter-Number Sequencing, Matrix Reasoning); attention/information processing (AIP; TMT-A, TMT-Motor, Digit Symbol); and memory (CVLT-II Trials 1–5 Total, Delayed Free Recall, Recognition Discriminability). Linear regressions between FSRP-10 and connectome ROIs adjusting for word reading, intracranial volume, and white matter hyperintensities revealed negative associations with nodal strength in eight ROIs (p-values<. 05) and negative associations with efficiency in two ROIs, and a positive association in one ROI (p-values<. 05). There was mediation of bilateral hippocampal strength on FSRP-10 and AIP, and left rostral middle frontal gyrus strength on FSRP-10 and AIP and EF. Stroke risk plays differential roles in connectivity and cognition, suggesting the importance of multi-modal neuroimaging biomarkers in understanding age-related CVD-RF burden and brain-behavior.

YNICL Journal 2016 Journal Article

Shared white matter alterations across emotional disorders: A voxel-based meta-analysis of fractional anisotropy

• Lisanne Michelle Jenkins
• Alyssa Barba
• Miranda Campbell
• Melissa Lamar
• Stewart A. Shankman
• Alex D. Leow
• Olusola Ajilore
• Scott Aaron Langenecker

BACKGROUND: White matter (WM) integrity may represent a shared biomarker for emotional disorders (ED). Aims: To identify transdiagnostic biomarkers of reduced WM by meta-analysis of findings across multiple EDs. METHOD: Mapping (SDM) Version 4.31. Separate meta-analyses were also conducted for each disorder. RESULTS: In the transdiagnostic meta-analysis, reduced FA was identified in ED studies compared to HCs in the left inferior fronto-occipital fasciculus, forceps minor, uncinate fasciculus, anterior thalamic radiation, superior corona radiata, bilateral superior longitudinal fasciculi, and cerebellum. Disorder-specific meta-analyses revealed the OCD group had the most similarities in reduced FA to other EDs, with every cluster of reduced FA overlapping with at least one other diagnosis. The PTSD group was the most distinct, with no clusters of reduced FA overlapping with any other diagnosis. The BD group were the only disorder to show increased FA in any region, and showed a more bilateral pattern of WM changes, compared to the other groups which tended to demonstrate a left lateralized pattern of FA reductions. CONCLUSIONS: Distinct diagnostic categories of ED show commonalities in WM tracts with reduced FA when compared to HC, which links brain networks involved in cognitive and affective processing. This meta-analysis facilitates an increased understanding of the biological markers that are shared by these ED.

YNIMG Journal 2011 Journal Article

Down syndrome with and without dementia: An in vivo proton Magnetic Resonance Spectroscopy study with implications for Alzheimer's disease

• Melissa Lamar
• Catherine M.L. Foy
• Felix Beacher
• Eileen Daly
• Michaela Poppe
• Nicola Archer
• Vee Prasher
• Kieran C. Murphy

It is poorly understood why people with Down syndrome (DS) are at extremely high-risk of developing Alzheimer's disease (AD) compared to the general population. One explanation may be related to their extra copy of risk factors modulated by chromosome 21. Myo-inositol (mI), whose transporter gene is located on chromosome 21, has been associated with dementia in the non-DS population; however, nobody has contrasted brain mI in DS with (DS+) and without (DS−) dementia to other non-DS groups. Our primary aim was to compare the hippocampal concentration of mI ([mI]) and other brain metabolites such as N-acetylaspartate (NAA; a proxy measure of neuronal density and mitochondrial function) in DS+, DS−, and age-matched healthy controls using proton Magnetic Resonance Spectroscopy ( 1 H-MRS). We compared hippocampal [mI] and other metabolites in 35 individuals with genetically-confirmed DS [DS+ (n=17, age=53±6) and DS− (n=18, age=47±8)] to age-matched healthy controls (n=13, age=51±10) adjusting for proportion of the MRS voxel occupied by cerebrospinal spinal fluid, and gray/white matter. DS+ had a significantly higher [mI] than both DS− and healthy controls. In contrast neither DS+ nor DS− differed significantly from controls in [NAA] (although NAA in DS+ was significantly lower than DS−). Our secondary aim of comparing brain metabolites in DS+ and DS− to Alzheimer's disease (AD; n=39; age=77±5) revealed that the DS+ group had significantly elevated [mI] compared to AD or DS−. [mI] may modify risk for dementia in this vulnerable population.

YNIMG Journal 2004 Journal Article

Age differences in orbitofrontal activation: an fMRI investigation of delayed match and nonmatch to sample

• Melissa Lamar
• David M Yousem
• Susan M Resnick