Wei Chen

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Alzheimers disease (AD) imaging
cognition

• Wei Chen
• CCNI Journal Club

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Alzheimers disease(AD)

• About 4 million people in the U.S. have AD.
• Nearly 10 of people 65 years of age and older
  are affected by AD.
• It is estimated that by 2050, 14 million
  Americans will have this disease and the number
  could increase to 45 million in the world.
• Its best to start treatment early.

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Definition of terms

• AD patients with clinically probable AD
  according to NINCDS-ADRDA (McKhann et al., 1984)
  or DSMIV (American Psychiatric Association, 1994)
  criteria.
• Mild AD Patients with probable AD at a mild
  stage of global cognitive impairment as assessed
  by MMSE gt20 and/or a CDR score 1.
• Accuracy postmortem, biopsy or genetics.

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Amygdala, Hippocampus and AD

• Medial temporal lobe (MTL) structures have been
  reported to be involved earliest and most
  extensively in the pathology of AD.

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Schematic diagram of the projections within the
medial temporal lobe ( A) A more detailed
diagram of (B). Adapted from Lavenex and Amaral
(2000).
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Functional neuroimaging
The identification of an abnormality in the
hippocampus or amygdala with non-invasive
imaging( mainly fMRI) is important as it could
facilitate the diagnosis of AD as well as
monitoring the treatment effect of certain drugs
on AD and may enable us to visualize these early
brain changes in the living subject.
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Fox elicited fear response --positive (Red) and
negative (blue) Bold in rats Brain
Olfactory bulb
Prefrontal cortex
hypothalamus
Amygdala and hippocampus were involved in the
emotional processing
amygdala
thalamus
hippocampus
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Prolongation of T2 relaxation times of
hippocampus and amygdala in AD Huali Wang, etc.
Neuroscience Letters 363 (2004) 150153.
showed the AD patients had longer T2 in
hippocampus and amygdala than vascular dementia
(VaD) subjects and healthy elderly controls.
Linear regression analysis showed that, in AD,
the right hippocampal T2 was correlated with
Alzheimers Disease Assessment Scale Cognitive
Subscale (ADAS-Cog )scores (r 0.495, Plt0.001
Fig. 1),.
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Mapping hippocampal and ventricular change in
ADPaul M. Thompson, etc. NeuroImage 22 (2004)
,1754 1766.

• The study has two goals
• (1) to map 3D profiles of hippocampal and
  ventricular change over time and compare them in
  AD and healthy elderly subjects.
• (2) to map where these changes correlate with
  cognitive decline.

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Methods

• Used longitudinal MRI scanning (two scans
  baseline and follow-up) and cognitive testing to
  study a group of AD subjects as their disease
  progressed.
• A second, demographically matched group of
  healthy elderly control subjects was also imaged
  longitudinally (two scans) as they aged normally.

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MRI scanning in this paper

• 3D T1-weighted images were acquired with an
  inversion recovery segmented 3D gradient echo
  sequence to resolve anatomy at high resolution.
• Images were acquired in an oblique plane
  perpendicular to the long axis of the hippocampus
  with an acquisition matrix of 256 x 256 x 96 and
  zero filled to 2563.

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Longitudinal ventricular maps (Mapping temporal
horn dilatation).
The top row shows an average temporal horn model
made for healthy controls at baseline (left) and
at follow-up (right). The color shows a measure
of local enlargement. The same maps in AD
(second row) show greatly enlarged and
progressively expanding temporal horns. The
bottom row shows a color-coded map of statistics
that reveal the significance of the group
difference (AD vs. controls) at each time point.
Most regions of the left temporal horn, and much
of the right, show evidence for greater expansion
in AD. Permutation testing is used to assign an
overall P value to the mapped effect , confirming
its significance.

P.M. Thompson et al. / NeuroImage 22 (2004)
17541766
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Longitudinal hippocampal maps (Mapping 3D
hippocampal atrophy).
The top row shows an average 3D hippocampal model
made for healthy controls at baseline (left) and
at follow-up (right). The color shows a measure
of local atrophy. The same maps in AD (second
row) show atrophied and progressively shrinking
hippocampi. The bottom row shows a color-coded
map of statistics that reveals the significance
of the group difference (AD vs. controls) at each
time point. Isolated regions of the left
hippocampal head show evidence for greater
atrophy in AD. Permutation testing is used to
assign an overall P value to the mapped
effect. P.M. Thompson et al. / NeuroImage 22
(2004) 17541766
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Mapping cognitive linkages
These maps (top left) show regions on the
temporal horns where expansion is associated with
worse performance on the MMSE. The hippocampal
maps (top right) show regions where contraction
is linked with worse MMSE performance. These are
cross-sectional comparisons based on baseline
scans. Loss of tissue in the left hippocampal
head links with lower MMSE scores. The final map
is based on a composite measure of hippocampal
atrophy divided by ventricular expansion. The
measure links more strongly with worse MMSE
performance (bottom left) than either of the
other maps assessed individually. These strong
links with declining cognition make these maps
practically useful as measures of disease
progression. P.M.
Thompson et al. / NeuroImage 22 (2004) 17541766
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Discussion

• Hippocampal volume reductions and ventricular
  expansions progressed over time, with different
  patterns in aging and dementia.
• Dynamic maps of the hippocampus and temporal
  horns may be potential biomarkers of AD
  progression.
• The maps better localize disease effects and may
  help identify factors that speed up or slow down
  brain degeneration in clinical trials or genetic
  studies of dementia.
• P.M. Thompson et al. / NeuroImage 22 (2004)
  17541766

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AD Outlook

• Treatment of AD includes five major components
  neuroprotective strategies, cholinesterase
  inhibitors, nonpharmacologic interventions and
  psychopharmacologic agents to reduce behavioral
  disturbances, health maintenance activities, and
  an alliance between clinicians and family members
  and other caregivers responsible for the
  patient.(n engl j med 3511, www.nejm.org july 1,
  2004)

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• The loss of cholinergic neurons within the basal
  forebrain is a major event in the development of
  AD symptomology. This decrease in acetylcholine
  (ACh) activity is linked to the cognitive decline
  seen in AD patients and many therapies rely on
  replacing the lost levels of ACh in the brain (J
  Neurol Neurosurg Psychiatry 199966137147).
  Using fMRI to study the relationship
  between nicotinic acetylcholine receptors (nAChR)
  and AD is of critical importance in the future.

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Thanks!!