Associations between neuropsychiatric symptoms, white matter microstructural integrity, and diagnostic status in the spectrum of Alzheimer’s disease

Abstract BackgroundWe aimed to systematically describe the burden and distribution of white matter hyperintensities (WMH) and investigate correlations with neuropsychiatric symptoms in pathologically proven Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD).MethodsAutopsy-confirmed cases were identified from the Sunnybrook Dementia Study, including 15 cases of AD and 58 cases of FTLD (22 FTLD-TDP cases; 10 FTLD-Tau [Pick's] cases; 11 FTLD-Tau Corticobasal Degeneration cases; and 15 FTLD-Tau Progressive Supranuclear Palsy cases). Data analyses included ANCOVA to compare the burden of WMH on antemortem brain MRI between groups and adjusted linear regression models to identify associations between WMH burden and neuropsychiatric symptoms. ResultsBurden and regional distribution of WMH differed significantly between neuropathological groups (F5,77 = 2.67, P’ = 0.029), with the FTLD-TDP group having the highest mean volume globally (8,031.50 ± 8,889.15 mm3) and in frontal regions (4,897.45 ± 6,163.22 mm3). The AD group had the highest mean volume in occipital regions (468.25 ± 420.04 mm3). Total score on the Neuropsychiatric Inventory correlated with bilateral frontal WMH volume (β = 0.330, P = 0.006), depression correlated with bilateral occipital WMH volume (β = 0.401, P < 0.001), and apathy correlated with bilateral frontal WMH volume (β = 0.311, P = 0.009), all corrected for the false discovery rate. ConclusionsThese findings suggest that WMH are associated with neuropsychiatric manifestations in AD and FTLD and that WMH burden and regional distribution in neurodegenerative disorders differ according to the underlying neuropathological processes.

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The use of diffusion-tensor imaging to assess microstructural integrity of white matter of patients with Alzheimer’s disease

Journal of radiology and nuclear medicine ◽

10.20862/0042-4676-2018-99-6-295-304 ◽

2019 ◽

Vol 99 (6) ◽

pp. 295-304

Author(s):

V. A. Perepelov ◽

V. I. Solodovnikov ◽

V. E. Sinitsyn ◽

E. M. Perepelova ◽

N. N. Koberskaya ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Diffusion Tensor Imaging ◽

White Matter ◽

Diffusion Tensor ◽

Small Vessel Disease ◽

Posterior Part ◽

Mean Diffusivity ◽

Imaging Protocol ◽

Microstructural Integrity

Objective. To compare diffusion-tensor imaging (DTI) measures in different anatomic regions of the brain in patients with an isolated Alzheimer's disease (AD) and patients with AD and small-vessel disease (SVD).Material and methods. 20 AD patients, aged 66 (±10), of whom 11 AD patients had an isolated neurodegenerative process and 9 patients, who were diagnosed with AD+SVD, were examined. A research was made on a 3 T Siemens Magnetom Skyra MR-scanner. All participants underwent the same imaging protocol, which included standard clinical- and diffusion tensor pulse sequences. With an MR-image processing software package Olea Medical Sphere 3.0, fractional anisotropy (FA), mean diffusivity (MD), axial and radial diffusivity (AxD and RxD) were measured in different brain regions.Results. Significant differences in DTI measures (FA, MD, AxD, RxD), indicating more severe white matter microstructural damage in AD+SVD patients, compared with patients with an isolated AD, were observed in middle thalamic radiation, upper and lower longitudinal bundles, posterior part of cingulate gyrus and genu of corpus callosum.Conclusion. DTI is an informative method, highly sensitive in detecting difference in white matter microstructural integrity of brain tissue in individuals with an isolated AD and patients with AD+SVD.

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White matter hyperintensities in autopsy-confirmed frontotemporal lobar degeneration and Alzheimer’s disease

Alzheimer s Research & Therapy ◽

10.1186/s13195-021-00869-6 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Philippe Desmarais ◽

Andrew F. Gao ◽

Krista Lanctôt ◽

Ekaterina Rogaeva ◽

Joel Ramirez ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

White Matter ◽

Frontotemporal Lobar Degeneration ◽

White Matter Hyperintensities ◽

Neuropsychiatric Symptoms ◽

Brain Mri ◽

Regional Distribution ◽

Linear Regression Models ◽

Image Guided

Abstract Background We aimed to systematically describe the burden and distribution of white matter hyperintensities (WMH) and investigate correlations with neuropsychiatric symptoms in pathologically proven Alzheimer’s disease (AD) and frontotemporal lobar degeneration (FTLD). Methods Autopsy-confirmed cases were identified from the Sunnybrook Dementia Study, including 15 cases of AD and 58 cases of FTLD (22 FTLD-TDP cases; 10 FTLD-Tau [Pick’s] cases; 11 FTLD-Tau Corticobasal Degeneration cases; and 15 FTLD-Tau Progressive Supranuclear Palsy cases). Healthy matched controls (n = 35) were included for comparison purposes. Data analyses included ANCOVA to compare the burden of WMH on antemortem brain MRI between groups, adjusted linear regression models to identify associations between WMH burden and neuropsychiatric symptoms, and image-guided pathology review of selected areas of WMH from each pathologic group. Results Burden and regional distribution of WMH differed significantly between neuropathological groups (F5,77 = 2.67, P’ = 0.029), with the FTLD-TDP group having the highest mean volume globally (8032 ± 8889 mm3) and in frontal regions (4897 ± 6163 mm3). The AD group had the highest mean volume in occipital regions (468 ± 420 mm3). Total score on the Neuropsychiatric Inventory correlated with bilateral frontal WMH volume (β = 0.330, P = 0.006), depression correlated with bilateral occipital WMH volume (β = 0.401, P < 0.001), and apathy correlated with bilateral frontal WMH volume (β = 0.311, P = 0.009), all corrected for the false discovery rate. Image-guided neuropathological assessment of selected cases with the highest burden of WMH in each pathologic group revealed presence of severe gliosis, myelin pallor, and axonal loss, but with no distinguishing features indicative of the underlying proteinopathy. Conclusions These findings suggest that WMH are associated with neuropsychiatric manifestations in AD and FTLD and that WMH burden and regional distribution in neurodegenerative disorders differ according to the underlying neuropathological processes.

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Surface-based vertexwise analysis of morphometry and microstructural integrity for white matter tracts in diffusion tensor imaging: With application to the corpus callosum in Alzheimer's disease

Human Brain Mapping ◽

10.1002/hbm.23491 ◽

2017 ◽

Vol 38 (4) ◽

pp. 1875-1893 ◽

Cited By ~ 8

Author(s):

Xiaoying Tang ◽

Yuanyuan Qin ◽

Wenzhen Zhu ◽

Michael I. Miller

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Diffusion Tensor Imaging ◽

White Matter ◽

Corpus Callosum ◽

Diffusion Tensor ◽

White Matter Tracts ◽

Microstructural Integrity

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White matter hyperintensities and neuropsychiatric symptoms in Alzheimer’s disease and mild cognitive impairment

10.1101/791657 ◽

2019 ◽

Author(s):

Karen Misquitta ◽

Mahsa Dadar ◽

D. Louis Collins ◽

Maria Carmela Tartaglia ◽

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

White Matter ◽

Cerebrovascular Disease ◽

Grey Matter ◽

White Matter Hyperintensities ◽

Neuropsychiatric Symptoms ◽

Grey Matter Atrophy

AbstractBackground and Purpose: Neuropsychiatric symptoms (NPS) are frequently encountered in patients with Alzheimer’s disease (AD). Focal grey matter atrophy has been linked to NPS development. Cerebrovascular disease can cause focal lesions and is common among AD patients. As cerebrovascular disease can be detected on MRI as white matter hyperintensities (WMH), this study evaluated WMH burden in mild cognitive impairment (MCI), AD and normal controls and determined their relationship with NPS. Methods: NPS were assessed using the Neuropsychiatric Inventory and grouped into subsyndromes. WMH were measured using an automatic segmentation technique and mean deformation-based morphometry was used to measure atrophy of grey matter regions. Results: WMHs and grey matter atrophy both contributed significantly to NPS subsyndromes in MCI and AD subjects, however, WMH burden played a greater role. Conclusions: This study could provide a better understanding of the pathophysiology of NPS in AD.

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