Patterns of progressive atrophy vary with age in Alzheimer's disease patients

Age is not only the greatest risk factor for Alzheimer's disease (AD) but also a key modifier of disease presentation and progression. Here, we investigate how longitudinal atrophy patterns vary with age in mild cognitive impairment (MCI) and AD. Data comprised serial longitudinal 1.5-T magnetic resonance imaging scans from 153 AD, 339 MCI, and 191 control subjects. Voxel-wise maps of longitudinal volume change were obtained and aligned across subjects. Local volume change was then modeled in terms of diagnostic group and an interaction between group and age, adjusted for total intracranial volume, white-matter hyperintensity volume, and apolipoprotein E genotype. Results were significant at p < 0.05 with family-wise error correction for multiple comparisons. An age-by-group interaction revealed that younger AD patients had significantly faster atrophy rates in the bilateral precuneus, parietal, and superior temporal lobes. These results suggest younger AD patients have predominantly posterior progressive atrophy, unexplained by white-matter hyperintensity, apolipoprotein E, or total intracranial volume. Clinical trials may benefit from adapting outcome measures for patient groups with lower average ages, to capture progressive atrophy in posterior cortices.

• Publication year

  2018

• Venue

  Neurobiology of Aging

• Publication date

  2018-03-01

• Fields of study

  Medicine

• Identifiers
  DOI 10.1016/j.neurobiolaging.2017.11.002PMID 29220823PMCID 5805840
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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• Variables associated with hippocampal atrophy rate in normal aging and mild cognitive impairment.

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  2014influential reference
• Operationalizing hippocampal volume as an enrichment biomarker for amnestic mild cognitive impairment trials: effect of algorithm, test-retest variability, and cut point on trial cost, duration, and sample size.

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• Fast and accurate modelling of longitudinal and repeated measures neuroimaging data

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• Different patterns of gray matter atrophy in early- and late-onset Alzheimer's disease.

  2013influential reference
• Symmetric Diffeomorphic Modeling of Longitudinal Structural MRI

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• Longitudinal changes of cortical thickness in early- versus late-onset Alzheimer's disease.

  2013influential reference
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• Multiscale adaptive generalized estimating equations for longitudinal neuroimaging data

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  2013influential reference
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• Multiscale Adaptive Marginal Analysis of Longitudinal Neuroimaging Data with Time‐Varying Covariates

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• Rates of Decline in Alzheimer Disease Decrease with Age

  2012influential reference
• Neuroimaging correlates of pathologically defined subtypes of Alzheimer's disease: a case-control study.

  2012influential reference
• Brain MAPS: An automated, accurate and robust brain extraction technique using a template library

  2011cited by this paper
• Heterogeneity in age-related white matter changes

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• Early-onset versus late-onset Alzheimer's disease: the case of the missing APOE ɛ4 allele.

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• Neuropathologically defined subtypes of Alzheimer's disease with distinct clinical characteristics: a retrospective study.

  2011influential reference
• Volume changes in Alzheimer’s disease and mild cognitive impairment: cognitive associations

  2010cited by this paper
• Everything You Never Wanted to Know about Circular Analysis, but Were Afraid to Ask

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• Automated cross-sectional and longitudinal hippocampal volume measurement in mild cognitive impairment and Alzheimer's disease

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• Neuroimaging Enrichment Strategy for Secondary Prevention Trials in Alzheimer Disease

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• Sex and age differences in atrophic rates: an ADNI study with n=1368 MRI scans.

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• Vascular risk factors and dementia

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• Cerebrospinal fluid biomarker signature in Alzheimer's disease neuroimaging initiative subjects

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• Fully-Automated White Matter Hyperintensity Detection with Anatomical Prior Knowledge and without FLAIR

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• VASCULAR RISK FACTORS AND DEMENTIA: HOW TO MOVE FORWARD?

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• Issues with threshold masking in voxel-based morphometry of atrophied brains

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• Hippocampal atrophy rates in Alzheimer disease

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• The Alzheimer's disease neuroimaging initiative (ADNI): MRI methods

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• Optimizing the design of clinical trials where the outcome is a rate. Can estimating a baseline rate in a run‐in period increase efficiency?

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• A fast diffeomorphic image registration algorithm

  2007influential reference
• The topography of grey matter involvement in early and late onset Alzheimer's disease.

  2007influential reference
• Precuneus atrophy in early-onset Alzheimer’s disease: a morphometric structural MRI study

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• Hippocampal atrophy in Alzheimer disease: Age matters

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• Four subgroups of Alzheimer's disease based on patterns of atrophy using VBM and a unique pattern for early onset disease

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• White matter lesion progression, brain atrophy, and cognitive decline: The Austrian stroke prevention study

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• Structural correlates of early and late onset Alzheimer’s disease: voxel based morphometric study

  2004influential reference
• The analysis of repeated ‘direct’ measures of change illustrated with an application in longitudinal imaging

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• Alzheimer’s disease: differences in technetium-99m HMPAO SPECT scan findings between early onset and late onset dementia

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• Genetic Risk Factors

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• Rates and risk factors for dementia and Alzheimer’s disease

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• APOE genotype predicts when — not whether — one is predisposed to develop Alzheimer disease

  1998cited by this paper
• A nonparametric method for automatic correction of intensity nonuniformity in MRI data

  1998cited by this paper
• Clinical and neuropsychological characteristics in familial and sporadic Alzheimer's disease

  1996cited by this paper
• Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families.

  1993cited by this paper
• Compensation for surface coil sensitivity variation in magnetic resonance imaging.

  1988cited by this paper

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• Uncovering atrophy progression pattern and mechanisms in individuals at risk of Alzheimer's disease

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• The characteristics of brain atrophy prior to the onset of Alzheimer’s disease: a longitudinal study

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• Regional deep atrophy: Using temporal information to automatically identify regions associated with Alzheimer’s disease progression from longitudinal MRI

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• Machine Learning-Derived MRI-Based Neurodegeneration Biomarker for Alzheimer’s Disease: A Multi-Database Validation Study

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