Radiological-Pathological Correlation in Alzheimer’s Disease: Systematic Review of Antemortem Magnetic Resonance Imaging Findings

Dallaire‐Théroux, Caroline; Callahan, Brandy L.; Potvin, Olivier; Saïkali, Stéphan; Duchesne, Simon

doi:10.3233/jad-161028

Cited by 54 publications

(63 citation statements)

References 71 publications

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“…There is evidence that soluble precursors of insoluble NFTs (tau oligomers) and APs (amyloid-ß oligomers) track disease progression (43) and have neurotoxic, and potentially synergistic capacities that operate independent of their downstream counterparts (ie, NFTs and APs) (5). Consistent with most observations made in DAT-AD (16), the distributions of dense-core APs did not mirror the neurodegenerative processes in PPA-AD. Since it has been shown that APs do not parallel disease progression in DAT-AD (3), one potential reason for this discordance could be that the accumulation or clearing of APs occur at rates dissimilar to the rate of atrophy in the time elapsed between the final MRI scan and death.…”

Section: Discussionsupporting

confidence: 87%

“…Cortical atrophy might be an intermediate feature of disease progression, emerging after a substantial accumulation of neuropathology, but preceding or concurrent to prominent clinical deficits . NFTs appear to be the stronger correlate of cortical atrophy in DAT‐AD , but it is not clear if this relationship is present in non‐amnestic presentations of AD. The current study sought to determine the relationships between in vivo cortical atrophy, AP densities, and NFT densities in PPA‐AD.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies examining DAT-AD and PPA-AD participants presented with several shortcomings that may have clouded the reported relationships between AD neuropathology and in vivo atrophy. For example, many of these investigations included wide interval ranges (intervals = ~1-8 years) between the final MRI scan and death (11,12,14,16,18,34,37,38,40,41,74,79,81), a potential problem since rates of atrophy and neuropathologic accumulations have yet to be clarified and atrophy likely worsened over the longer intervals. Measurements of atrophy were often confined to the hippocampus (11,12,14,18,34,37,38,41,74,79), whole-brain volume (14,18,40,41,74), or ventricular volumes (18,40,41,74), making it difficult to generalize the neuropathologic-anatomic relationships across brain regions.…”

Section: Introductionmentioning

confidence: 99%

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Neuropathologic basis of in vivo cortical atrophy in the aphasic variant of Alzheimer's disease

et al. 2019

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The neuropathologic basis of in vivo cortical atrophy in clinical dementia syndromes remains poorly understood. This includes primary progressive aphasia (PPA), a language‐based dementia syndrome characterized by asymmetric cortical atrophy. The neurofibrillary tangles (NFTs) and amyloid‐ß plaques (APs) of Alzheimer's disease (AD) can cause PPA, but a quantitative investigation of the relationships between NFTs, APs and in vivo cortical atrophy in PPA‐AD is lacking. The present study measured cortical atrophy from corresponding bilateral regions in five PPA‐AD participants with in vivo magnetic resonance imaging scans 7–30 months before death and acquired stereologic estimates of NFTs and dense‐core APs visualized with the Thioflavin‐S stain. Linear mixed models accounting for repeated measures and stratified by hemisphere and region (language vs. non‐language) were used to determine the relationships between cortical atrophy and AD neuropathology and their regional selectivity. Consistent with the aphasic profile of PPA, left language regions displayed more cortical atrophy (P = 0.01) and NFT densities (P = 0.02) compared to right language homologues. Left language regions also showed more cortical atrophy (P < 0.01) and NFT densities (P = 0.02) than left non‐language regions. A subset of data was analyzed to determine the predilection of AD neuropathology for neocortical regions compared to entorhinal cortex in the left hemisphere, which showed that the three most atrophied language regions had greater NFT (P = 0.04) and AP densities (P < 0.01) than the entorhinal cortex. These results provide quantitative evidence that NFT accumulation in PPA selectively targets the language network and may not follow the Braak staging of neurofibrillary degeneration characteristic of amnestic AD. Only NFT densities, not AP densities, were positively associated with cortical atrophy within left language regions (P < 0.01) and right language homologues (P < 0.01). Given previous findings from amnestic AD, the current study of PPA‐AD provides converging evidence that NFTs are the principal determinants of atrophy and clinical phenotypes associated with AD.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Neuropathologic basis of in vivo cortical atrophy in the aphasic variant of Alzheimer's disease

et al. 2019

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“…21 Neuropathological and brain magnetic resonance imaging (MRI) studies suggest that decreased vascular density occurs with aging and Alzheimer's disease, and these changes precede the onset of cognitive dysfunction and neurodegeneration. 22 There is also a decline in cerebrovascular angiogenesis, which may inhibit recovery from hypoxia-induced capillary loss. Cerebral blood flow may then be further inhibited by tortuous arterioles and deposition of excessive collagen in the veins and venules.…”

Section: Cerebral Microvascular Diseasementioning

confidence: 99%

Microvascular Disease and Small-Vessel Disease: The Nexus of Multiple Diseases of Women

Patel

Aggarwal

Rao

et al. 2020

Journal of Women's Health

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Microvascular disease, or small-vessel disease, is a multisystem disorder with a common pathophysiological basis that differentially affects various organs in some patients. The prevalence of small-vessel disease in the heart has been found to be higher in women compared with men. Additionally, other diseases prominently affecting women, including heart failure with preserved ejection fraction, Takotsubo cardiomyopathy, cerebral small-vessel disease, preeclampsia, pulmonary arterial hypertension (PAH), endothelial dysfunction in diabetes, diabetic cardiomyopathy, rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis, may have a common etiologic linkage related to microvascular disease. To the best of our knowledge this is the first article to investigate this potential linkage. We sought to identify various diseases with a shared pathophysiology involving microvascular/endothelial dysfunction that primarily affect women, and their potential implications for disease management. Advanced imaging technologies, such as magnetic resonance imaging and positron-emission tomography, enable the detection and increased understanding of microvascular dysfunction in various diseases. Therapies that improve endothelial function, such as those used in PAH, may also be associated with benefits across the full spectrum of microvascular dysfunction. A shared pathology across multiple organ systems highlights the need for a collaborative, multidisciplinary approach among medical subspecialty practitioners who care for women with small-vessel disease. Such an approach may lead to accelerated research in diseases that affect women and their quality of life.

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“…WMH refer to regions in the white matter that appear hyperintense on T2 fluid attenuated inversion recovery (FLAIR) sequences. The etiologies of WMH are multifaceted (e.g., gliosis, axonal loss) [9–15], but WMH accompany aging and cardiovascular disease and are often presumed to be of vascular origin and reflect small vessel cerebrovascular disease (CBVD) [9,16–21]. International consensus-based guidelines emphasize the pathologies underlying WMH (along with cerebral amyloid angiopathy [CAA], microbleeds, microinfarcts, among others) as mechanisms of vascular cognitive impairment (VCI) [22].…”

Section: Introductionmentioning

confidence: 99%

A Clinicopathological Investigation of White Matter Hyperintensities and Alzheimer’s Disease Neuropathology

Alosco

Sugarman

Besser

et al. 2018

JAD

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Background: White matter hyperintensities (WMH) on magnetic resonance imaging have been postulated to be a core feature of Alzheimer’s disease. Clinicopathological studies are needed to elucidate and confirm this possibility. Objective: This study examined: 1) the association between ante-mortem WMH and autopsy-confirmed Alzheimer’s disease neuropathology (ADNP), 2) the relationship between WMH and dementia in participants with ADNP, and 3) the relationships among cerebrovascular disease, WMH and ADNP. Methods: The sample included 82 participants from the National Alzheimer’s Coordinating Center’s Data Sets who had quantitated volume of WMH from ante-mortem FLAIR MRI and available neuropathological data. The Clinical Dementia Rating (CDR) scale (from MRI visit) operationalized dementia status. ADNP+ was defined by moderate to frequent neuritic plaques and Braak stage III-VI at autopsy. Cerebrovascular disease neuropathology included infarcts or lacunes, microinfarcts, arteriolosclerosis, atherosclerosis, and cerebral amyloid angiopathy. Results: 60/82 participants were ADNP+. Greater volume of WMH predicted increased odds for ADNP (p=0.037). In ADNP+ participants, greater WMH corresponded with increased odds for dementia (CDR≥1; p=0.038). WMH predicted cerebral amyloid angiopathy, microinfarcts, infarcts and lacunes (p’s<0.04). ADNP+ participants were more likely to have moderate-severe arteriolosclerosis and cerebral amyloid angiopathy compared to ADNP− participants (p’s<0.04). Conclusions: This study found a direct association between total volume of WMH and increased odds for having ADNP. In patients with Alzheimer’s disease, FLAIR MRI WMH may be able to provide key insight into disease severity and progression. The association between WMH and ADNP may be explained by underlying cerebrovascular disease.

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Radiological-Pathological Correlation in Alzheimer’s Disease: Systematic Review of Antemortem Magnetic Resonance Imaging Findings

Abstract: Cerebral atrophy and white matter changes in the living brain reflect underlying neuropathology and may be detectable using antemortem MRI. In vivo MRI may therefore be an avenue for AD pathological staging.

Cited by 54 publications

References 71 publications

Neuropathologic basis of in vivo cortical atrophy in the aphasic variant of Alzheimer's disease

Neuropathologic basis of in vivo cortical atrophy in the aphasic variant of Alzheimer's disease

Microvascular Disease and Small-Vessel Disease: The Nexus of Multiple Diseases of Women

A Clinicopathological Investigation of White Matter Hyperintensities and Alzheimer’s Disease Neuropathology

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