Faculty Bibliography
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87
Intracranial artery stenosis is associated with cortical thinning in stroke-free individuals of two longitudinal cohorts
BACKGROUND:We examined the association between asymptomatic intracranial artery stenosis (aICAS) and cortical thickness using brain magnetic resonance morphometry in two cohorts. METHODS:This cross-sectional study included stroke-free participants from the Northern Manhattan Study (NOMAS) and the National Alzheimer's Coordinating Center (NACC). We represented the predictor aICAS in NOMAS as a continuous global stenosis score reflecting an overall burden of stenosis (possible range 0-44) assessed by magnetic resonance angiography and in NACC as a dichotomous autopsy-determined Circle of Willis (CoW) atherosclerosis (none-mild vs moderate-severe). The primary outcome of interest was total cortical thickness. We analyzed each dataset separately using multivariable linear regression. RESULTS:The analysis included 1209 NOMAS (46% had any stenosis, 5% had ≥70% stenosis of at least one vessel; stenosis score range 0-11) and 392 NACC (36% moderate-severe CoW atherosclerosis) participants. We found an inverse relationship between stenosis score and total cortical thickness (β-estimate [95% confidence interval (CI)]: -2.98 [-5.85, -0.11]) in adjusted models. We replicated these results in NACC (β-estimate [95% CI]: -0.06 [-0.11, -0.003]). Post-hoc, we segregated stenosis scores by location and only posterior circulation stenosis score was associated with total cortical thickness (anterior β-estimate [95% CI]: -0.90 [-5.16, 3.36], posterior β-estimate [95% CI]: -7.25 [-14.30, -0.20]). CONCLUSION/CONCLUSIONS:We found both radiographically and neuropathologically determined aICAS to be associated with global cortical thinning. Interestingly, posterior circulation stenoses appeared to drive this association with global cortical thinning, raising the possibility of pathophysiologic mechanisms for cortical thinning other than impaired hemodynamics.
PMCID:9880900
PMID: 36577280
ISSN: 1878-5883
CID: 5409642
Clinical Implications of Internal Carotid Arterial Tortuosity in Patients with White Matter Hyperintensities
Background: White matter hyperintensities (WMHs) are observed frequently on MRI in elderly and associated with cognitive dysfunction. Many studies focused on intracranial small vessel disease (SVD), however, few studies linked WMHs with changes of extracranial large feeding arteries. We aimed to investigate the effects of internal carotid artery (ICA) tortuosity changes through quantitative MR Angiography. Method: Fifty-seven patients (age: 72.98±5.62; 32 females/25 males) with WMHs were included. WMHs lesions were semi-automatically segmented on FLAIR images. ICAs were segmented on the TOF images to generate tortuosity quantitative metrics, including tortuosity index (TI), inflection count metric (ICM), and ICA angle (Figure 1). According to the Fazekas scores, patients were categorized into mild, moderate and severe groups as summarized in Table 1. One-way ANOVA analyses were applied to reveal the difference of averaged bilateral ICAs' tortuosity measurements. Pearson's correlation coefficients were calculated to quantitatively investigate the relationship between tortuosity and volumes of lesions that are apart from the ventricle in subcortical white matter, i.e., deep white matter lesions (DWMLs), as well as the lesions attached with the ventricular system, i.e., periventricular white matter lesions (PVWMLs). Result: Patients with higher Fazekas scores have higher TI and ICM, indicating higher tortuosity (Figure 2). The correlation results showed that TI and ICM were positively correlated with DWMLs volumes (r = 0.33, P< 0.05; r = 0.4, P< 0.01), however, they did not show associations with PVWMLs. While there's no correlation between averaged bilateral ICA angles and DWMLs or PVWMLs, we found significant correlations between left ICA angles and DWML volumes on left brain (r =0.56, P < 0.005) as well as between right ICA angles and DWML volumes on right brain (r = 0.49, P < 0.05) (Figure 3). Conclusion: Tortuosity measurements derived from TOF images showed that subjects with higher degree of ICA tortuosity had higher lesion volumes of DWMLs not PVWMLs, indicating DWMLs may have different etiologies such as ischemic origin. The findings also highlight the importance of ICA angle as a risk factor for WMHs development which might be associated with the local hemodynamic shear stress at the bulb, where the ICA plaques are often developed.
SCOPUS:85144449727
ISSN: 1552-5260
CID: 5393902
Cortical Myelin Profile Variations in Healthy Aging Brain: A T1w/T2w Ratio Study
Demyelination is observed in both healthy aging and age-related neurodegenerative disorders. While the significance of myelin within the cortex is well acknowledged, studies focused on intracortical demyelination and depth-specific structural alterations in normal aging are lacking. Using the recently available Human Connectome Project Aging dataset, we investigated intracortical myelin in a normal aging population using the T1w/T2w ratio. To capture the fine changes across cortical depths, we employed a surface-based approach by constructing cortical profiles traveling perpendicularly through the cortical ribbon and sampling T1w/T2w values. The curvatures of T1w/T2w cortical profiles may be influenced by differences in local myeloarchitecture and other tissue properties, which are known to vary across cortical regions. To quantify the shape of these profiles, we parametrized the level of curvature using a nonlinearity index (NLI) that measures the deviation of the profile from a straight line. We showed that NLI exhibited a steep decline in aging that was independent of local cortical thinning. Further examination of the profiles revealed that lower T1w/T2w near the gray-white matter boundary and superficial cortical depths were major contributors to the apparent NLI variations with age. These findings suggest that demyelination and changes in other T1w/T2w related tissue properties in normal aging may be depth-specific and highlight the potential of NLI as a unique marker of microstructural alterations within the cerebral cortex.
PMID: 36368498
ISSN: 1095-9572
CID: 5357642
Generalizable deep learning model for early Alzheimer's disease detection from structural MRIs
Early diagnosis of Alzheimer's disease plays a pivotal role in patient care and clinical trials. In this study, we have developed a new approach based on 3D deep convolutional neural networks to accurately differentiate mild Alzheimer's disease dementia from mild cognitive impairment and cognitively normal individuals using structural MRIs. For comparison, we have built a reference model based on the volumes and thickness of previously reported brain regions that are known to be implicated in disease progression. We validate both models on an internal held-out cohort from The Alzheimer's Disease Neuroimaging Initiative (ADNI) and on an external independent cohort from The National Alzheimer's Coordinating Center (NACC). The deep-learning model is accurate, achieved an area-under-the-curve (AUC) of 85.12 when distinguishing between cognitive normal subjects and subjects with either MCI or mild Alzheimer's dementia. In the more challenging task of detecting MCI, it achieves an AUC of 62.45. It is also significantly faster than the volume/thickness model in which the volumes and thickness need to be extracted beforehand. The model can also be used to forecast progression: subjects with mild cognitive impairment misclassified as having mild Alzheimer's disease dementia by the model were faster to progress to dementia over time. An analysis of the features learned by the proposed model shows that it relies on a wide range of regions associated with Alzheimer's disease. These findings suggest that deep neural networks can automatically learn to identify imaging biomarkers that are predictive of Alzheimer's disease, and leverage them to achieve accurate early detection of the disease.
PMCID:9576679
PMID: 36253382
ISSN: 2045-2322
CID: 5352422
Reduced white matter venous density on MRI is associated with neurodegeneration and cognitive impairment in the elderly
High-resolution susceptibility weighted imaging (SWI) provides unique contrast to small venous vasculature. The conspicuity of these mesoscopic veins, such as deep medullary veins in white matter, is subject to change from SWI venography when venous oxygenation in these veins is altered due to oxygenated blood susceptibility changes. The changes of visualization in small veins shows potential to depict regional changes of oxygen utilization and/or vascular density changes in the aging brain. The goal of this study was to use WM venous density to quantify small vein visibility in WM and investigate its relationship with neurodegenerative features, white matter hyperintensities (WMHs), and cognitive/functional status in elderly subjects (N = 137). WM venous density was significantly associated with neurodegeneration characterized by brain atrophy (β = 0.046± 0.01, p < 0.001), but no significant association was found between WM venous density and WMHs lesion load (p = 0.3963). Further analysis of clinical features revealed a negative trend of WM venous density with the sum-of-boxes of Clinical Dementia Rating and a significant association with category fluency (1-min animal naming). These results suggest that WM venous density on SWI can be used as a sensitive marker to characterize cerebral oxygen metabolism and different stages of cognitive and functional status in neurodegenerative diseases.
PMCID:9475309
PMID: 36118685
ISSN: 1663-4365
CID: 5335222
Early-Stage MRI Volumetric Differences in White Matter Hyperintensity and Temporal Lobe Volumes between Autopsy-Confirmed Alzheimer's Disease, Cerebral Small Vessel Disease, and Mixed Pathologies
Introduction/UNASSIGNED:Alzheimer's disease (AD) and cerebral small vessel disease (CVSD) both contribute to age-related cognitive decline but can be difficult to clinically distinguish at early stages. At mild cognitive impairment (MCI), we investigated brain MRI volumetric differences in white matter hyperintensities (WMH), frontal and temporal lobe volumes between neuropathologically defined groups of cerebral arteriolosclerosis alone (pARTE), AD alone (pAD), and mixed (ADARTE). Methods/UNASSIGNED:= 55) who had MRI brain volumetrics within 1 year of clinical evaluation with Clinical Dementia Rating score of 0.5, corresponding to MCI. We included moderate-to-severe arteriolosclerosis and/or ABC score 2-3 for AD, after excluding other major neuropathologies. We compared WMH and frontal and temporal lobe volumes between neuropathology groups using regression analysis. Results/UNASSIGNED:Adjusted regression models show AD-related groups associated with less WMH when compared to pARTE (pAD adjusted odds ratio (aOR) (95% confidence interval [CI]): 0.94 (0.90-0.98); ADARTE aOR (95% CI): 0.96 (0.93-0.99)). The mixed pathology group, but not pAD, had smaller right temporal lobe volumes than pARTE (pAD aOR [95% CI]: 0.86 [0.74-1.00]; ADARTE aOR [95% CI]: 0.83 [0.72-0.96]). There were no differences in frontal lobe volumes. Discussion/Conclusions/UNASSIGNED:Findings from this neuropathologically confirmed cohort suggest volumetric differences in WMH and temporal lobe volumes between AD- and CVSD-related MCI. Moreover, our results suggest a differential atrophy susceptibility of the right versus left temporal lobe to the additive effect of AD and vascular pathologies.
PMCID:9149438
PMID: 35702161
ISSN: 1664-5464
CID: 5282642
Concordance between self- and collateral-reported memory loss in mild cognitive impairment due to Alzheimer's versus cerebrovascular disease [Meeting Abstract]
Background: The importance of informant history in the diagnosis of mild cognitive impairment (MCI) has been emphasized. Yet, there is limited literature looking into the agreement of self- and informant- reported memory loss in MCI due to Alzheimer's disease (AD) versus cerebrovascular disease (CVD). We investigated the hypothesis that rates of concordance and discordance differ based on MCI etiology.
Method(s): Retrospective clinical data was gathered from the National Alzheimer's Coordinating Center dataset. First visits with a clinical diagnosis of MCI with a primary etiology of AD without CVD (AD MCI) or CVD without AD (CVD MCI) were included for analysis. Self- and informant-based report of memory loss were gleaned from the questions "does the subject report a decline in memory (relative to previously attained abilities?)" and "does the co-participant report a decline in subject's memory (relative to previously attained abilities?)." We excluded participants with missing self-reported or co-participant information on cognitive decline. Statistical analysis was performed using Chi-squared tests.
Result(s): A total of 1917 AD MCI and 213 CVD MCI visits from unique participants were included in the study. Compared to CVD MCI, AD MCI had a higher incidence of visits where both participant and informant noted memory loss (67.8% vs. 54.0%, p<0.0001). Compared to AD MCI, CVD MCI featured more disagreement between participant and informant, both in cases where the participant denied memory loss (17.8% vs. 12.0%, p = 0.0137) and where the informant denied memory loss (21.6% vs. 11.4%, p < 0.0001). Incidence of both participant and informant denying memory loss were similar between AD MCI and CVD MCI (8.9% vs. 6.6%, p = 0.2580).
Conclusion(s): Self- and collateral-based report of memory loss are more discordant in CVD MCI versus AD MCI. This reinforces the importance of eliciting a history from both patients and reliable informants, especially in patients with vascular risk factors and comorbidities
Method(s): Retrospective clinical data was gathered from the National Alzheimer's Coordinating Center dataset. First visits with a clinical diagnosis of MCI with a primary etiology of AD without CVD (AD MCI) or CVD without AD (CVD MCI) were included for analysis. Self- and informant-based report of memory loss were gleaned from the questions "does the subject report a decline in memory (relative to previously attained abilities?)" and "does the co-participant report a decline in subject's memory (relative to previously attained abilities?)." We excluded participants with missing self-reported or co-participant information on cognitive decline. Statistical analysis was performed using Chi-squared tests.
Result(s): A total of 1917 AD MCI and 213 CVD MCI visits from unique participants were included in the study. Compared to CVD MCI, AD MCI had a higher incidence of visits where both participant and informant noted memory loss (67.8% vs. 54.0%, p<0.0001). Compared to AD MCI, CVD MCI featured more disagreement between participant and informant, both in cases where the participant denied memory loss (17.8% vs. 12.0%, p = 0.0137) and where the informant denied memory loss (21.6% vs. 11.4%, p < 0.0001). Incidence of both participant and informant denying memory loss were similar between AD MCI and CVD MCI (8.9% vs. 6.6%, p = 0.2580).
Conclusion(s): Self- and collateral-based report of memory loss are more discordant in CVD MCI versus AD MCI. This reinforces the importance of eliciting a history from both patients and reliable informants, especially in patients with vascular risk factors and comorbidities
EMBASE:637954287
ISSN: 1531-5487
CID: 5252432
American journal of respiratory & critical care medicine. 2022:206(5):632-636.DOI: 10.1164/rccm.202201-0107LE
Obstructive Sleep Apnea and Hypertension with Longitudinal β-Amyloid Burden and Cognitive Changes
PMID: 35550019
ISSN: 1535-4970
CID: 5213082
New insights into the genetic etiology of Alzheimer's disease and related dementias
Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele.
PMCID:9005347
PMID: 35379992
ISSN: 1546-1718
CID: 5213092
International journal of environmental research & public health. 2022:19(6).DOI: 10.3390/ijerph19063440
Cognitive Function among World Trade Center-Exposed Community Members with Mental Health Symptoms
The World Trade Center Environmental Health Center (WTC EHC), is a federally designated clinical center of excellence for surveillance and treatment of WTC disaster exposed community members (WTC Survivors). Cognitive impairment (CI) has been extensively described in WTC responders and a concern for progressive impairment in all WTC disaster exposed groups has been raised. Cognitive status, however, has not been systematically characterized in the WTC Survivor population. We describe cognitive status in a subgroup of the Survivor population referred for mental health evaluation (N = 480) in the WTC EHC as measured by scores on the Montreal Cognitive Assessment (MoCA) instrument, and examine their association with WTC exposures and individual-level covariates including PTSD and depression screening inventory scores. In regression analyses, probable cognitive impairment (MoCA score < 26) was found in 59% of the study subjects and was significantly associated with age, race/ethnicity, education, income, depression and PTSD scores. Being caught in the dust cloud on 11 September 2011 was significantly associated with cognitive impairment even after controlling for the above. These data suggest an association with cognitive dysfunction in WTC Survivors with exposure to the toxic dust/fumes and psychological stress from the 9/11 terrorist attack and warrant further systematic study.
PMCID:8948727
PMID: 35329128
ISSN: 1660-4601
CID: 5184832
