Longitudinal tau-PET uptake and atrophy in atypical Alzheimer's disease

Irene Sintini, Peter R. Martin, Jonathan Graff-Radford, Matthew L. Senjem, Christopher G. Schwarz, Mary Margaret Machulda, Anthony J. Spychalla, Daniel A. Drubach, David S Knopman, Ronald Carl Petersen, Val Lowe, Clifford R Jr. Jack, Keith Anthony Josephs, Jennifer Lynn Whitwell

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

The aims of this study were: to examine regional rates of change in tau-PET uptake and grey matter volume in atypical Alzheimer's disease (AD); to investigate the role of age in such changes; to describe multimodal regional relationships between tau accumulation and atrophy. Thirty atypical AD patients underwent baseline and one-year follow-up MRI, [ 18 F]AV-1451 PET and PiB PET. Region- and voxel-level rates of tau accumulation and grey matter atrophy relative to cognitively unimpaired individuals, and the influence of age on such rates, were assessed. Univariate and multivariate analyses were performed between baseline measurements and rates of change, between baseline tau and atrophy, and between the two rates of change. Regional patterns of change in tau and volume differed, with highest rates of tau accumulation in frontal lobe and highest rates of atrophy in temporoparietal regions. Age had a negative effect on disease progression, predominantly on tau, with younger patients having a more rapid accumulation. Baseline tau uptake and regions of tau accumulation were disconnected, with high baseline tau uptake across the cortex correlated with high rates of tau accumulation in frontal and sensorimotor regions. In contrast, baseline volume and atrophy were locally related in the occipitoparietal regions. Higher tau uptake at baseline was locally related to higher rates of atrophy in frontal and occipital lobes. Tau accumulation rates positively correlated with rates of atrophy. In summary, our study showed that tau accumulation and atrophy presented different regional patterns in atypical AD, with tau spreading into the frontal lobes while atrophy remains in temporoparietal and occipital cortex, suggesting a temporal disconnect between protein deposition and neurodegeneration.

Original languageEnglish (US)
Article number101823
JournalNeuroImage: Clinical
Volume23
DOIs
StatePublished - Jan 1 2019

Fingerprint

Atrophy
Alzheimer Disease
Frontal Lobe
Occipital Lobe
Disease Progression
Multivariate Analysis
Proteins

Keywords

  • Atrophy
  • Atypical AD
  • Longitudinal tau-PET
  • Multimodal imaging

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Neurology
  • Clinical Neurology
  • Cognitive Neuroscience

Cite this

Longitudinal tau-PET uptake and atrophy in atypical Alzheimer's disease. / Sintini, Irene; Martin, Peter R.; Graff-Radford, Jonathan; Senjem, Matthew L.; Schwarz, Christopher G.; Machulda, Mary Margaret; Spychalla, Anthony J.; Drubach, Daniel A.; Knopman, David S; Petersen, Ronald Carl; Lowe, Val; Jack, Clifford R Jr.; Josephs, Keith Anthony; Whitwell, Jennifer Lynn.

In: NeuroImage: Clinical, Vol. 23, 101823, 01.01.2019.

Research output: Contribution to journalArticle

@article{650722325a0b43a3b9831b1444bbca37,
title = "Longitudinal tau-PET uptake and atrophy in atypical Alzheimer's disease",
abstract = "The aims of this study were: to examine regional rates of change in tau-PET uptake and grey matter volume in atypical Alzheimer's disease (AD); to investigate the role of age in such changes; to describe multimodal regional relationships between tau accumulation and atrophy. Thirty atypical AD patients underwent baseline and one-year follow-up MRI, [ 18 F]AV-1451 PET and PiB PET. Region- and voxel-level rates of tau accumulation and grey matter atrophy relative to cognitively unimpaired individuals, and the influence of age on such rates, were assessed. Univariate and multivariate analyses were performed between baseline measurements and rates of change, between baseline tau and atrophy, and between the two rates of change. Regional patterns of change in tau and volume differed, with highest rates of tau accumulation in frontal lobe and highest rates of atrophy in temporoparietal regions. Age had a negative effect on disease progression, predominantly on tau, with younger patients having a more rapid accumulation. Baseline tau uptake and regions of tau accumulation were disconnected, with high baseline tau uptake across the cortex correlated with high rates of tau accumulation in frontal and sensorimotor regions. In contrast, baseline volume and atrophy were locally related in the occipitoparietal regions. Higher tau uptake at baseline was locally related to higher rates of atrophy in frontal and occipital lobes. Tau accumulation rates positively correlated with rates of atrophy. In summary, our study showed that tau accumulation and atrophy presented different regional patterns in atypical AD, with tau spreading into the frontal lobes while atrophy remains in temporoparietal and occipital cortex, suggesting a temporal disconnect between protein deposition and neurodegeneration.",
keywords = "Atrophy, Atypical AD, Longitudinal tau-PET, Multimodal imaging",
author = "Irene Sintini and Martin, {Peter R.} and Jonathan Graff-Radford and Senjem, {Matthew L.} and Schwarz, {Christopher G.} and Machulda, {Mary Margaret} and Spychalla, {Anthony J.} and Drubach, {Daniel A.} and Knopman, {David S} and Petersen, {Ronald Carl} and Val Lowe and Jack, {Clifford R Jr.} and Josephs, {Keith Anthony} and Whitwell, {Jennifer Lynn}",
year = "2019",
month = "1",
day = "1",
doi = "10.1016/j.nicl.2019.101823",
language = "English (US)",
volume = "23",
journal = "NeuroImage: Clinical",
issn = "2213-1582",
publisher = "Elsevier BV",

}

TY - JOUR

T1 - Longitudinal tau-PET uptake and atrophy in atypical Alzheimer's disease

AU - Sintini, Irene

AU - Martin, Peter R.

AU - Graff-Radford, Jonathan

AU - Senjem, Matthew L.

AU - Schwarz, Christopher G.

AU - Machulda, Mary Margaret

AU - Spychalla, Anthony J.

AU - Drubach, Daniel A.

AU - Knopman, David S

AU - Petersen, Ronald Carl

AU - Lowe, Val

AU - Jack, Clifford R Jr.

AU - Josephs, Keith Anthony

AU - Whitwell, Jennifer Lynn

PY - 2019/1/1

Y1 - 2019/1/1

N2 - The aims of this study were: to examine regional rates of change in tau-PET uptake and grey matter volume in atypical Alzheimer's disease (AD); to investigate the role of age in such changes; to describe multimodal regional relationships between tau accumulation and atrophy. Thirty atypical AD patients underwent baseline and one-year follow-up MRI, [ 18 F]AV-1451 PET and PiB PET. Region- and voxel-level rates of tau accumulation and grey matter atrophy relative to cognitively unimpaired individuals, and the influence of age on such rates, were assessed. Univariate and multivariate analyses were performed between baseline measurements and rates of change, between baseline tau and atrophy, and between the two rates of change. Regional patterns of change in tau and volume differed, with highest rates of tau accumulation in frontal lobe and highest rates of atrophy in temporoparietal regions. Age had a negative effect on disease progression, predominantly on tau, with younger patients having a more rapid accumulation. Baseline tau uptake and regions of tau accumulation were disconnected, with high baseline tau uptake across the cortex correlated with high rates of tau accumulation in frontal and sensorimotor regions. In contrast, baseline volume and atrophy were locally related in the occipitoparietal regions. Higher tau uptake at baseline was locally related to higher rates of atrophy in frontal and occipital lobes. Tau accumulation rates positively correlated with rates of atrophy. In summary, our study showed that tau accumulation and atrophy presented different regional patterns in atypical AD, with tau spreading into the frontal lobes while atrophy remains in temporoparietal and occipital cortex, suggesting a temporal disconnect between protein deposition and neurodegeneration.

AB - The aims of this study were: to examine regional rates of change in tau-PET uptake and grey matter volume in atypical Alzheimer's disease (AD); to investigate the role of age in such changes; to describe multimodal regional relationships between tau accumulation and atrophy. Thirty atypical AD patients underwent baseline and one-year follow-up MRI, [ 18 F]AV-1451 PET and PiB PET. Region- and voxel-level rates of tau accumulation and grey matter atrophy relative to cognitively unimpaired individuals, and the influence of age on such rates, were assessed. Univariate and multivariate analyses were performed between baseline measurements and rates of change, between baseline tau and atrophy, and between the two rates of change. Regional patterns of change in tau and volume differed, with highest rates of tau accumulation in frontal lobe and highest rates of atrophy in temporoparietal regions. Age had a negative effect on disease progression, predominantly on tau, with younger patients having a more rapid accumulation. Baseline tau uptake and regions of tau accumulation were disconnected, with high baseline tau uptake across the cortex correlated with high rates of tau accumulation in frontal and sensorimotor regions. In contrast, baseline volume and atrophy were locally related in the occipitoparietal regions. Higher tau uptake at baseline was locally related to higher rates of atrophy in frontal and occipital lobes. Tau accumulation rates positively correlated with rates of atrophy. In summary, our study showed that tau accumulation and atrophy presented different regional patterns in atypical AD, with tau spreading into the frontal lobes while atrophy remains in temporoparietal and occipital cortex, suggesting a temporal disconnect between protein deposition and neurodegeneration.

KW - Atrophy

KW - Atypical AD

KW - Longitudinal tau-PET

KW - Multimodal imaging

UR - http://www.scopus.com/inward/record.url?scp=85064253404&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85064253404&partnerID=8YFLogxK

U2 - 10.1016/j.nicl.2019.101823

DO - 10.1016/j.nicl.2019.101823

M3 - Article

VL - 23

JO - NeuroImage: Clinical

JF - NeuroImage: Clinical

SN - 2213-1582

M1 - 101823

ER -