Early diagnosis of Alzheimers disease: contribution of structural neuroimaging

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Early diagnosis of Alzheimers disease
contribution of structural neuroimaging

• Gaël Chetelat and Jean-Claude Baron
• NeuroImage 18 (2003)

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Paper Overview

• Motivation for MCI ? AD prediction problem
• Methodologies for
• Defining MCI
• Delineating ROIs
• Assessing atrophy
• Study results
• Cross-sectional
• Mild AD vs. HAS
• At-risk (MCI and others) vs. HAS
• Longitudinal
• MCI ? AD vs. MCI ? MCI

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Anatomy
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Motivation
AD is characterized by the spread of
neurofibrillary tangles (NFTs) and ? protein
deposits in these areas
Perirhinal cortex
Entorhinal cortex
Hippocampus
Rest of TL
time
Association Areas
Entire Cortex
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Motivation
Cognitive signs
Unaltered cognitive state
Perirhinal cortex
Some memory complaints
Entorhinal cortex
Hippocampus
Dementia
Rest of TL
time
Association Cortex
Entire Cortex
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Motivation
May work better here
Perirhinal cortex
Treatment AchE Inhibitors
Entorhinal cortex
Hippocampus
Usually administered here
Rest of TL
time
Association Cortex
Entire Cortex
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Motivation

• Want Good detectors of early AD
• Possibilities
• Levels of ? protein and amyloid A?42 in CSF
• Loss of smell
• Imaging markers

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Motivation
Other diseases
Normal aging
AD (6-8)
time
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Motivation
High AD risk
AD
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Longitudinal Studies
Discriminate these from these
AD
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Cross-Sectional Studies
Discriminate these from these
AD
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High AD Risk

• Family History
• Age
• APOE-?4
• Mild cognitive deficits

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What is MCI?

• No clear consensus yet--many definitions
• Memory-related AAMI, Petersen MCI-A criteria
• Multiple-cognitive-domain-related AACD, ARCD,
  MCD
• Often defined by grading scales CDR .5, GDS
  3
• Petersen MCI-A criteria
• Memory complaint
• Normal daily activities
• Normal general cognitive function
• Abnormal memory for age
• No Dimentia

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Delineating ROIs
Variable, ambiguous, tedious, manual
Perirhinal cortex
More reliable, fast, (semi) automatic
Entorhinal cortex
Hippocampus
Rest of TL
time
Association Cortex
Entire Cortex
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Assessing Atrophy

• Visual inspection
• Line measurements
• Surface measurements
• Volume measurements

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Cross-Sectional Studies Mild AD vs. Controls

• Significant atrophy in Hcp/Phcp volume between
  groups
• Looks promising
• Entor. Cortex volume
• Entor. temporal neocortex volume
• Jury still out on the amygdala
• Fair performance as a discriminator Hcp
• Poor performance Phcp, lateral temporal cortex,
  frontal cortex

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Cross-Sectional At-Risk vs. AD vs. Controls

• Mild cognitive deficits
• AAMI Hcp volume not s.d. from HAS Hcp volume
  higher than AD
• MCI Hcp and entor. volumes lower than HAS
• APOE-?4
• Hcp volume not s.d. from HAS annual volume loss
  greater vs. HAS

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Longitudinal Studies MCI ? AD vs. MCI ? MCI

• Significant differences in
• Dilatation (stretching) of perihippocampal
  fissure
• Volumes of Phcp, Entor., Hcp, fusiform gyrus
• Entor. volume
• No significant differences in
• Volumes of LTL, TL, rest of cortex
• Annual Hcp atrophy rate (2)
• Good predictors
• Memory scores Phcp volume (96)
• Hcp fusiform gyrus TL volumes (96)
• Hcp LTL volumes (80)
• STLAC volumes ()

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Limitations to Longitudinal Studies

• Small samples
• Inclusion criteria
• Wide age range
• Over-inclusive cognitive criteria (CDR, GDS)
• ROI delineation
• Inaccurate, arbitrary, ambiguous
• Atrophy assessment
• Subjective, qualitative measures
• Weak scanning equipment (e.g., .6 T)