Post on 09-Apr-2022
transcript
08/11/2019
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Normal aging and brain atrophy
Meike Vernooij, MD PhD
Professor of Population ImagingRadiology & Nuclear Medicine; Epidemiology
Erasmus University Medical Center
Rotterdam, The Netherlands
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Example of report
Request: 77‐yr old male, subjective memory complaints. Q: pathology?
Phrase from brain MRI report:
“There is loss of brain volume normal for age”
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What is ‘normal for age’?
The Radiologist’s perspective
• We are used to assess abnormality, not normality.
• Age‐related changes are non‐acute…
…and thus not of interest.
• Usually no clinical question addressing ageing.
• Lack of proper frame of reference.
• Aging is a dynamic process.
“ atrophy unremarkable for age”
“ nonspecific leukoaraiosis”
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The Epidemiologist’s perspective
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• Populations are ageing, so is age‐related brain pathology!
The Neuroscientist’s perspective
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• Characteristic changes of brain aging are also strongly linked to neurodegeneration.
• ‘Normal ageing’ may form a spectrum with neurodegeneration.
• Succesful versus less successful ageing likely influenced by genetic, lifestyle and environmental factors.
What happens in the brain in aging? MICROSCOPY
• amyloid plaques• neurofibrillary tangles• Lewy bodies• neuronal loss• ependymal loss• iron deposition• subependymal gliosis• myelin loss• axonal degeneration• microvascular pathology• …..
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NEURODEGENERATION
CEREBROVASCULAR DISEASE
NORMAL PATHOLOGICAL
Age‐related brain changesIMAGING
• atrophy
• white matter disease
• cerebral microbleeds
• silent brain infarcts
• enlarged perivascular spaces
• iron deposition
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Brain atrophy: normal?
• Loss of brain tissue occurs after age of 30: 0.2%/year.
• Acceleration after age 70: 0.5%/year.
• At age 75: 10% loss of brain tissue compared to age 30.
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Vinke et al.; Neurobiology of Aging 2018based on >4,000 Rotterdam Study subjects
What is abnormal?
o > 1‐2% tissue loss/ yr
o Regional atrophy/asymmetry
Atrophy: clinical assessment
• symmetric > asymmetric• generalized > focal• severity: visual assessment: global cortical atrophy (GCA)
GCA 0(none)
GCA 1(mild)
GCA 2(moderate)
GCA 3(severe)
no atrophy widening sulci volume loss gyri ‘knife‐blade’
Atrophy: clinical assessment
• symmetric > asymmetric• generalized > focal• severity: visual assessment: global cortical atrophy (GCA)
GCA 0(none)
GCA 1(mild)
GCA 2(moderate)
GCA 3(severe)
no atrophy widening sulci volume loss gyri ‘knife‐blade’
always abnormal
abnormal < 75 yr
Pasquier F, Eur Neurol 1997
no atrophy
widening choroid fissure
widening temporal horn
↓ hippocampal volume
↓↓ hippocampal volume
Severity
0 1 2 3 4
Scheltens et al. 1992
Hippocampus: what is normal?
Medial temporal atrophy (MTA) scale
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no atrophy
widening choroid fissure
widening temporal horn
↓ hippocampal volume
↓↓ hippocampal volume
Severity
0 1 2 3 4
Scheltens et al. 1992
Hippocampus: what is normal?
What is abnormal?
o Up to 75 yr: MTA ≥ 2 on one side
o Over 75 yr: MTA ≥ 2 on both sides
Atrophy: change over time?
2009 20112010
11%124 ml
10%111 ml
9%100 ml
What is normal?
References values derived from normal aging population
Ikram et al., Neurobiol of Aging 2008 Vrooman et al., NeuroImage 2006
What is normal ?
Brain volume (% IC
V)
60
90
70
80
50 60 70 80 90 100
Age
95%
75%
50%
25%
5%
t=0
t=5
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40
30
20
10
50
%
00 1 2 3 4 5 6 7 8 9
45 ‐ 59 y60 ‐ 74 y74 ‐ 97 y
white matter lesion severity (categories)
De Leeuw et al., JNNP 2001
White matter hyperintensities
Wardlaw Lancet Neurology 2013
White matter disease: terminology
“WMH OF PRESUMED VASCULAR ORIGIN”
White matter lesions and cognition
de Groot et al., Annals of Neurology 2002 Prins et al., Archives of Neurology 2004
dementia risk
cognitive decline
Fazekas 1
Fazekas 2
Fazekas 3
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Fazekas 1
Fazekas 2
Fazekas 3
What is abnormal?
o Diffuse confluent lesions (Fazekas 3)
o Rapid progression
I II III
Wattjes, Radiology 2009
WMH: MRI versus CT
FA De Groot et al.; Stroke 2013MD
2005 2008 2005 2008
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Normal ageing?
T2 FLAIR T2* GRE
male, 72 years
Microbleeds
amyloid angiopathy (CAA) hypertension
Greenberg et al., Lancet Neurology 2009Vernooij et al.; Neurology 2008
Microbleeds: what is normal?
• prevalence > 20% in general population > 60 yrs.
• single microbleed in person considered not relevant.
• caveat: strong dependency on technology.
GRE SWI
Yamada; J Stroke 2015.
1.5 T 3.0 T
Microbleeds: what is normal?
• Boston criteria: ≥ 2 lobar (micro)bleeds = probable CAA1.
• multiple: relate to worse cognitive function.
• multiple: increased risk of stroke and dementia.1Knudsen; Stroke 2001.
Akoudad; Circulation 2015.
2013 2014
o Multiple CMBs: suggestSVD.
o Lobar: CAA.
o Deep: hypertension.
o Note imaging techniqueused.
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Silent brain infarcts
lacunes
Vermeer; Stroke 2002
• prevalence up to 30%
• size 3‐15 mm
• rim of gliosis
Silent?
o Lacune: suggest small vesseldisease
o Doubles risk of stroke anddementia
Newly recognized subtypes
corticalmicroinfarcts(6%)
small cerebellarinfarcts (11%)
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Ischemic lacune?
2011 2012
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Enlarged perivascular spaces Enlarged perivascular spaces• Typical locations:
– Mesencephalon
– Lenticulostriatal
– Subinsular
– CSO
• Relate to markers of small vessel disease.
• Worse cognition.
• Correlations with parenchymal amyloid deposition.
Zhu; Stroke 2010.Adams; Stroke 2013.Maclullich; JNP 2004.
Charimidou; Stroke 2015.
Enlarged perivascular spaces
hypertension
blockage
inflammation
atrophy
Charimidou; Stroke 2015. Roher; Mol Med 2003.
Zhu; Stroke 2010. Satizabal; JAD 2012. Kress; Ann. Neurol. 2014.
Zlokovic; Neuron 2008.
Weller; Brain path. 2008.
Patankar AJNR 2005.
État criblé
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Iron deposition in brain ageing
• essential element (ATP synthesis, myelin)
• accumulation in aging (> 20‐30 yrs): homeostaticdisturbance
• risk factors: age, smoking, hypertension, obesity
• accumulation oxidation, inflammationneurodegeneration
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• normal: globuspallidus, dentatenucleus
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• abnormal: excessivehypointensity, abnormal locations(pulvinar)
VARIABILITY:
* TECHNIQUE (FIELD STRENGTH)
* INTER‐INDIVIDUAL
QUANTIFICATION NEEDED
T2 FSE T2*
SWI-magnitude SWI-phase SWI-mIP
Iron versus calcification Checklist for normal brain aging
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• Brain atrophy: report MTA, GCA, lobar pattern, asymmetries. • GCA: score of 3 (‘knife‐blading’) always abnormal.• GCA: score of 2 abnormal in persons < 75 years.• MTA: score of 2 or higher on one side is abnormal in < 75 yrs• MTA: score of 2 or higher on both sides is abnormal in ≥ 75 yrs• WMH: report Fazekas scale, normal up to 1. • Fazekas: score of 2 or 3 suggests underlying small vessel disease.• Report presence of lacunar infarcts, cortical (micro)infarct, small
cerebellar infarcts.• Report enlarged perivascular spaces (basal ganglia, centrum
semiovale, mesencephalon, subinsular region). • Etat criblé is always abnormal.• Microbleeds: number and location (lobar versus deep). Mention
field strength and pulse sequence.
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Example of report
77‐yr old male, subjective memory complaints. Abnormal patterns of atrophy or vascular lesions?
Interpretation:• Mild generalised brain volume loss (GCA 1) in accordance with patient’s
age, no lobar preference, no asymmetry.• Mild hippocampal atrophy, MTA 1 on right, MTA 2 on left side, normal
for age.• Punctate WMH in periventricular and subcortical locations, Fazekas 1.• No lacunar or cortical infarcts. Single small cerebellar infarct on left
side.• Single lobar microbleed in right frontal lobe.
Conclusion:Mild degenerative and vascular brain changes, consistent with normal brain aging, no evidence for a neurodegenerative disorder.
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Take home points
• Age‐related brain changes can no longer be ignored.
• Understand that aging is a dynamic process.
• Use of reference values will become increasingly important for clinical interpretation.
• Many visible changes are only tip of the iceberg.
• Use checklist for reading and reporting brain scans in aging.
Today’s radiologist is prepared for tomorrow’s patients
m.vernooij@erasmusmc.nl
Thank you for your attention
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