Transcript Alzheimer disease

Advanced brain imaging and
neurodegenerative disorders.
Dott.ssa Ingrid Inches
www.ulss.tv.it
Neurodegenerative diseases are conventionally
diagnosed using clinical assessment,
neuropsychology tests and structural neuroimaging.
However, there is an increasing need for using
advanced mri techniques in order to better
assess early volumetric, methabolic, ultrastructural
and functional changes.
Understanding the pathophysiology of the diseases
may help in planning and monitoring therapy.
NEURODEGENERATIVE DISORDERS
- DEMENTIAS
- EXTRAPYRAMIDAL DISORDERS
- MOTOR NEURON DISEASES
DEMENTIAS
Dementias have the gratest impact in health
management, among all neurodegenerative
disorders.
It is characterized by cognitive impairment severe
enough to interfere with activity of daily living.
Prevalence and incidence of dementias increase
with age of patients.
2,5 dementia cases x 1000 65 – 69 yrs
9 dementia cases x 1000 75 – 79 yrs
40, 2 dementia cases x 1000 85 – 89 yrs
Ramani, et al., Radiology 2006.
DEMENTIAS – Alzheimer’s disease
Prevalence of AD Dementia
Scheltens, Fox, Barkhof, DeCarli, Lancet Neurology 2002.
Dubois F, Feldman HF, Jacova C, DeKosky ST et al.
Research criteria for the diagnosis of Alzheimer’s
disease: revising the NINCDS – ADRDA criteria.
Lancet Neurol 2007; 6: 734-46
Probable AD:
CRITERION A: EARLY AND SIGNIFICANT EPISODIC
MEMORY IMPAIRMENT
at least one or more supportive biomarker criteria.
SUPPORTIVE CRITERIA
at least one or more supportive biomarker criteria.
B.
MTL ATROPHY
C.
GLUCOSE METABOLISM IN
BILATERAL
TEMPORAL REGIONS
D.
β AMYLOID
τ
E.
PROTEIN
STRUCTURAL NEUROIMAGING WITH MRI
MOLECULAR NEUROIMAGING WITH PET
CSF ANALYSIS
PROVEN AUTOSOMAL DOMINANT MUTATION WITHIN
THE IMMEDIATE FAMILY
CONVENTIONAL IMAGING –
Alzheimer’s disease
Linear measures of
atrophy in mild
Alzheimer disease.
Frisoni GB et al. AJNR 17 (1996)
913-23
CONTROLS
AD
1) MTL atrophy is common in AD
(71 – 96%) compared with
older NC subjects.
2) Width of the temporal horn
could discriminate AD vs NC
with sensitivity 86%
VBM - Alzheimer’s disease
Mapping local hippocampal changes in Alzheimer’s disease
and normal ageing with MRI at 3T.
R
L
Frisoni GB,et al. Brain 131 (2008) 3266 - 3276
1)sensitive to MTL atrophy in AD not
specific
2) sensitive to progression of the disease
L
R
3) volumes of AD patients tended to be
lower vs NC
4) medial, lateral regions in body and tail
were lower in older NC
5) AD dorsolateral head and presubiculum
DTI - Alzheimer’s disease
-DTI: white matter damage in
AD patients.
 MD and  FA in
corpus callosum and in WM
of frontal, temporal and
parietal lobes.
Strong correlation between
MMSE and WM FA - MD.
- In AD patients white matter
changes are likely to be
secondary to wallerian
degeneration due to
neuronal loss in cortical
Bozzali, Falini et al., JNNP 2002.
areas.
TRACTS - Alzheimer’s disease
Diffusion Anisotropy an Diffusivity of White Matter Tracts in the Temporal
Stem in AD disease: Evaluation of the “Tract of Interest” by Diffusion Tensor
Tractography .
T.Taoka, MD; et al. AJNR 27 (2006) 1040 -1045.
- 15 NC and 15 AD
“tract of interest” method
Alzheimer’s disease and MCI
Regional Degradation of White Matter Ultrastructure in Mild cognitive
impairment and Alzheimer’s disease by Diffusion Tensor Imaging.
-MCI is associated with FA
Y. Zhang, MD; et al. Neurology 68 (2007 ) 13 - 19.
reduction particularly in
the cingulum fibers,
predominantly in the left
posterior cingulate.
-In AD, FA is further
reduced in the cingulum
fibers and FA reduction
extend to the splenium.
-FA reduction in the
posterior cingulate
improved the classification
of MCI and AD from
cognitively normal
elderly, compared to the
classifications using
hippocampal volume loss
alone.
Alzheimer’s disease and MCI
Regionally-specific diffusion tensor imaging in Mild cognitive impairment and
Alzheimer’s disease.
M.M.Mielke, MD; et al. Neuroimage 46 (2009) 47 - 55.
-75 pts (25 NC, 25 aMCI, 25 AD)
-baseline and 3 months follow up
-AD vs NC reduction FA in fornix and
anterior cingulate
-MCI vs AD lower FA in fornix,
anterior cingulate, splenium
-Over 3 months follow- up further
decrease FA in anterior cingulate
-Decrease FA well correlated with
worse clinical performance.
Alzheimer’s disease and MCI
A diffusion tensor MRI study of patients with MCI an AD with a 2-year
clinical follow-up.
Scola E, Bozzali M, Agosta F, Falini A et al. J Neurol Neurosur
Psychiatry 2010 8; 798 – 805.
- 62 pts (21 aMCI, 21 AD, 20 NC)
- baseline and 2 years follow up
- aMCI-C had WM and GM changes similar to AD
- aMCI-NC showed DTI pattern similar to NC
- increase MD in hippocampi, anterior insulae,
frontal and parietal WM and decrease FA of
temporal WM better distinguished aMCI-C vs
aMCI-NC
H MRS - Alzheimer’s disease
Whole-brain N-Acetylaspartate as a surrogate Marker of Neuronal
Damage in diffuse Neurologic Disorders.
D.J. Rigotti et al. AJNR 28 (2007) 1843 -1849.
-NAA (single peak at 2.02) is the most
intense in a healthy brain.
- 25 NC, 28 AD, 27 MCI
significant decrease of WB NAA AD
vs NC but not between them (MCI –
AD).
Alzheimer’s disease and MCI
MCI
AD
H MR spectroscopy voxel in
posterior cingulate, superior-temporal
and parietal lobe.
-Decrease of NAA peak and increase
of Myo peak in AD and MCI vs NC.
-Increase of Myo peak in MCI vs NC
Kaantarci, Reynolds et al., AJNR 2003.
fMRI - Alzheimer’s disease
Functional MR imaging in Alzheimer’s Disease during
Memory Encoding.
S. Rombouts, F. Barkhof et al. AJNR 21 (2000) 1869 - 1875.
- fMRI testing the activation of MTL memory
- learning tasks that required the encoding of new information
into memory (familiar pictures vs novel pictures)
-12 AD 10 NC
- Decrease functional signal in MTL areas in AD vs NC
Alzheimer’s disease and MCI
Increased hippocampal activation in mild cognitive impairment
compared to normal aging and AD.
B.C. Dickerson, MD et al. Neurology 65 (2005) 404 - 411.
- 10 NC, 9 MCI, 10 AD
- fMRI with face-name task
- Hyperactivation in hippocampal and entorhinal cortex in MCI
- This pattern may reflect the need for memory circuits to recruit additional
neural resources in order to compensate early MTL memory – networks
degeneration.
Alzheimer’s disease and MCI
Cortical Deactivation in Mild Cognitive Impairment: High – Field –
Strength Functional MR Imaging.
J Petrella, MD et al. Radiology 245 (2007) 224 – 235.
-75 subjects - 13 AD
- 28 NC
- face–name associative memory encoding task : novel face – name pairs
familiar face – name pairs
 in signal intensity magnitude from NC, MCI, AD in
- left anterior cingulate gyrus
- left MTL ( hyppocampus)
 in signal magnitude from NC, MCI, AD in postero-medial cortices
(precuneus and posterior cyngulate gyrus).
- Increasing magnitude activation signal from NC to MCI to AD in PMC
- Loss of deactivation in PMC: abnormally activation in low default mode
network activity region.
- PMC: region attending to enviromental stimuli, planning future
behaviors and conscious processes.
fMRI resting state - Alzheimer’s
disease and MCI
Altered resting state networks in mild cognitive impairment and
mild Alzheimer’s disease: an fMRI study.
SA Rombouts, F Barkhof et al. Radiology 256 (2010) 598 – 606.
- 41 NC, 18 AD, 28 MCI
- MCI patients less deactivation vs NC but more vs AD
- Anterior frontal cortex default mode network distinguished MCI
from NC and AD.
- The response in the precuneus NC vs AD and MCI not MCI vs AD.
SWI - Alzheimer’s disease
Post-mortem biochemical studies (Connor et al, Neurobiol Aging 2004)
found out eccessive brain iron in cortical and basal ganglia region in
AD.
Oxidative damage to the brain
caused by free radical
reactions
catalized by iron could be
implicated in AD.
In AD entorhinal cortex could be a marker of iron.
SWI has been proposed as a means of measuring regional iron level.
Conclusions
Structural imaging based on magnetic resonance is an integral part
of the clinical assessment of patients with suspected Alzheimer
dementia.
Diffusion tensor, functional magnetic resonance imaging, and
resting/functional MRI have a relevant role as adjuncts to clinical
assessment in early diagnosis and monitoring of progression.
New growing interest in SWI-dependent imaging as a potential biomarker of the presence of iron in AD.
Alzheimer’s disease and MCI
Cortical Deactivation in Mild Cognitive Impairment: High – Field –
Strength Functional MR Imaging.
J Petrella, MD et al. Radiology 245 (2007) 224 – 235.
-75 subjects - 13 AD
- 28 NC
- face–name associative memory encoding task : novel face – name pairs
familiar face – name pairs
 in signal intensity magnitude from NC, MCI, AD in
- left anterior cingulate gyrus
- left MTL ( hyppocampus)
 in signal magnitude from NC, MCI, AD in postero-medial cortices
(precuneus and posterior cyngulate gyrus).
DEMENTIAS – Alzheimer disease
Conventionally neurodegenerative diseases are
diagnosed using clinical assessment,
neuropsychology and structural neuroimaging.
However there in an increasing need for using
advanced mri technique in order to better
asses early volumetric, methabolic, ultrastuctural
and functional changes helping to understand the
pathophysiology of the diseases and planning and
monitoring therapy.