Dataset Information

Neurodegenerative changes in early- and late-onset cognitive impairment with and without brain amyloidosis.

ABSTRACT:

Background

A substantial number of patients clinically diagnosed with Alzheimer's disease do not harbor amyloid pathology. We analyzed the presence and extent of tau deposition and neurodegeneration in amyloid-positive (AD) and amyloid-negative (nonAD) ADNI subjects while also taking into account age of onset (< or > 65 years) as we expected that the emerging patterns could vary by age and presence or absence of brain amyloidosis.

Methods

One hundred and ten early-onset AD (EOAD), 121 EOnonAD, 364 late-onset AD (LOAD), and 175 LOnonAD mild cognitive impairment (MCI) and dementia (DEM) subjects were compared to 291 ADNI amyloid-negative control subjects using voxel-wise regression in SPM12 with cluster-level family-wise error correction at p_FWE < 0.05). A subset of these subjects also received ¹⁸F-flortaucipir scans and allowed for analysis of global tau burden.

Results

As expected, relative to LOAD, EOAD subjects showed more extensive neurodegeneration and tau deposition in AD-relevant regions. EOnonAD_MCI showed no significant neurodegeneration, while EOnonAD_DEM showed bilateral medial and lateral temporal, and temporoparietal hypometabolism. LOnonAD_MCI and LOnonAD_DEM showed diffuse brain atrophy and a fronto-temporo-parietal hypometabolic pattern. LOnonAD and EOnonAD subjects failed to show significant tau binding.

Conclusions

LOnonAD subjects show a fronto-temporal neurodegenerative pattern in the absence of tau binding, which may represent underlying hippocampal sclerosis with TDP-43, also known as limbic-predominant age-related TDP-43 encephalopathy (LATE). The hypometabolic pattern observed in EOnonAD_DEM seems similar to the one observed in EOAD_MCI. Further investigation into the underlying etiology of EOnonAD is warranted.

SUBMITTER: Stage EC

PROVIDER: S-EPMC7409508 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Publications

Neurodegenerative changes in early- and late-onset cognitive impairment with and without brain amyloidosis.

Stage Eddie C EC Svaldi Diana D Phillips Meredith M Canela Victor Hugo VH Duran Tugce T Goukasian Naira N Risacher Shannon L SL Saykin Andrew J AJ Apostolova Liana G LG

Alzheimer's research & therapy 20200805 1

<h4>Background</h4>A substantial number of patients clinically diagnosed with Alzheimer's disease do not harbor amyloid pathology. We analyzed the presence and extent of tau deposition and neurodegeneration in amyloid-positive (AD) and amyloid-negative (nonAD) ADNI subjects while also taking into account age of onset (< or > 65 years) as we expected that the emerging patterns could vary by age and presence or absence of brain amyloidosis.<h4>Methods</h4>One hundred and ten early-onset AD (EOAD), ...[more]

PMID: 32758274

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Dataset Information

Neurodegenerative changes in early- and late-onset cognitive impairment with and without brain amyloidosis.

Background

Methods

Results

Conclusions

Publications

Neurodegenerative changes in early- and late-onset cognitive impairment with and without brain amyloidosis.

Similar Datasets

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