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Workshop: Neuroimaging in

old age psychiatry

“Bona diagnosis, bona curatio”

Mathieu Vandenbulcke

Old Age Psychiatry, University of Leuven

Disclosures

• I am not a radiologist!

Basic knowledge

for geriatric psychiatrist

• Normal ageing is visible in the brain

• Imaging characteristics of main causes of dementia

– AD

– FTD

– LBD

– VD

• Considerations and pitfalls in late life psychiatric

disorders

Normal Ageing

Heads of an old man and a youth, Leonardo Da Vinci,

ca. 1495. Galleria degli Uffizi, Firenze.Nelissen & Vandenbulcke, 2010

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Normal ageing

Hedden and Gabrieli, Nature Rev Neurosci, 2004

Alzheimer’s Disease

• Structural imaging: MRI

• Functional imaging: FDG PET

• Amyloid imaging

Alzheimer’s Disease

• Structural imaging: MRI

• Functional imaging: FDG PET

• Amyloid imaging

Topography of Alzheimer’s Disease

Hierarchical distribution of

neurofibrillary tangles and neuropil threads

Stage I & II

Transentorhinal stage

Stage III & IV

Limbic stage

Stage V & VI

Isocortical stage

Braak and Braak, Neuropathological stagein of Alzheimer-related

Changes. Acta Neuropathologica, 82, 239-259, 1991

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Structural changes on MRI:

coronale view on hippocampus

Height

fissura

choroidea

Width

temporal

horn

Height

hippocampus

0 nl nl nl

1 nl nl

2

3

4

Scheltens et al., J NNP, 1992

Hippocampal volume & AD

Fox, Lancet, 2001

24 Differential diagnosis: amnestic disorder

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Other components of memory circuitNeuroimaging of the Wernicke–

Korsakoff Syndrome

Sullivan et al., 2009

Alzheimer’s Disease

• Structural imaging: MRI

• Functional imaging: FDG PET

• Amyloid imaging

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Small, NEJM, 06

Functional imaging: FDG PET Functional imaging: FDG PET

• Clinical D/– Sensitivity 86%

– Specificity 86%

• Neuropathological D/

– Sensitivity: 88-90%

– Specificity: 62-74%

Alzheimer’s Disease

• Structural imaging: MRI

• Functional imaging: FDG PET

• Amyloid imaging

Theuns, Marjaux, Vandenbulcke et al. , Human Mutation , 2006

Molecular imaging in AD:PIB PET

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1 2 3 4 5

6 7 8 9 10

11 12 13 14 15

0

DVR

2

AD: Amyloid imaging (PIB PET)

AD

Nl

Nelissen, Vandenbulcke et al., Brain , 2007

1. Historiek begrip MCI

2. MCI & biomarkers

3. MCI & depressie

4. DSM V

Jack et al., Lancet Neurol, 2010

Villemagne et al., Lancet Neurol, 2013

Amyloid deposition in MCI

Nordberg et al., Eur J Nucl Med Mol Imaging. 2013

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Suspected

nonamyloid

pathology (SNAP)

in MCI

Caroli et al., Neurology 2015

Amyloid deposition in the oldest

old (82 to 96y)

Mathis et al., Ann Neurol. 2013

Differential diagnosis FTLD / AD

Rabinovici et al., Neurology , 2007

Summary imaging in AD

function:

FDG PET

structure:

MRI

pathology:

amyloid scan

Alzheimer’s disease

Healthy control t

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NIA/AA diagnostic criteria

MCI due to AD

research-criteria

Albert et al. Alzheimer’s & Dementia, 2011

Imaging in frontotemporal lobe

degeneration

FTD PNFASD

R L R L R L

Structural imaging: MRI of CT

Functional imaging: FDG PET (or SPECT) Imaging in Lewy Body Disease

McKeith et al., Lancet Neurology, 2007

LBD Non-LBD

Dopaminerg system

(123I-FP-CIT )FDG PET

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Imaging in vascular dementia1. Dementia

2. Cerebrovascular impairment: focal neurological signs &

cerebrovascular lesions (large vessel disease, multiple lacunar

infarcts, exentensive white matter damage) evidenced by neuroimaging

3. Relationship between 1 & 2

Roman et al., Neurology, Vascular dementia: Diagnostic criteria for

research studies, 43, 250-260, 1992

NINDS AIREN imaging criteria:

topography

• Small vessel disease

1. Extensive white matter lesions or

2. Multiple basal glia, thalamic and frontal

white matter lacunar infarcts:

1. ≥2 lacunar infarcts in the basal gglia, thalamus

or internal capsule, AND

2. ≥2 lacunar infarcts in the frontal white matter,

or

3. Bilateral thalamic lesions

FAZEKAS scale

Punctate foci Beginning

confluence

Large confluent

areas

Fazekas 1 Fazekas 2 Fazekas 3

Normal Abnormal <70y Always abnormal

Neuroimaging in dementia, Barkhof et al. 2011c

NINDS AIREN imaging criteria:

Severity

• Extensive leukoencephalopathy involving at

least ¼ of the total white matter:

– Confluent lesions in at least two regions, AND

– Beginning confluent in two other regions

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Neuroimaging in dementia, Barkhof et al. 2011

T2 GE FLAIR

??

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T2 GE FLAIRADVD LBD FTD

Late

Life

Depression

Dementia

Mild cognitive impairment (MCI)

Normal cognition

Late life depression & neuroimaging

Psychiatric

vulnerability

Environmental

factors

Loss of

brain function

Low

high

Threshold for late life

Psychiatric disorder

Normal ageing

Pathological ageing

Psychiatric

vulnerability

Environmental

factors

Loss of

brain function

Laag

Hoog

Threshold for late life

Psychiatric disorder

Normal ageing

Pathological ageing

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LLD and

hippocampus

Lloyd, O’Brien Br J Psychiatry. 2004

Hippocampal volumetry LLD

cohort Leuven: WIP

De Winter et al., In preparation

• WMHI

Alexopoulos et al. Am J Psychiatry, 1997

Firbank et al. Am J Geriatr Psychiatry 2004

Krishnan et al. Int J Geriatr Psychiatry, 2006

“Vascular depression” →

“subcortical ischemic depression ”White matter impairment &

late onset depression,

de Groot,, Arch Gen Psychiatry. 2000

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VALIDITY IS CONTROVERSIAL:

Vienna Transdanube Aging (VITA) Study

Rainer, Am J Geriatr Psychiatry. 2006

FDG PET and severe LLD

• 10 patients with therapy resistent late onset depression without

vascular impairment

• 10 controls

Fujimoto et al., Psychiatry Research: Neuroimaging 2008

FDG PET Univesity Hospital

Leuven LLD• Retrospective unpublished observational study 2006 – 2009

• 27 patients with D/ of LLD who underwent FDG PET

• D/ based on clinical evaluation, neuroimaging, neuropsychological

examination, FU minimally 12 months

Normal pattern in15/27 (55%)

Pattern suggestive for neurodegeneration in

12/27 (45%):

– 9/27 AD (33%)

– 2/27 FTD (7%)

– 1/27 LBD (4%)

MAINLY NEGATIVE

PREDICTIVE VALUE?

Amyloid imaging in LLD

• 9 subjects, 7 fullfilled criteria of MCI

• PIB PET: 2 nl, 3 AD pattern, 3 intermediary

pattern, 1 exclusion

Butters et al., Alzheimer Dis Assoc Disord , 2008

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Amyloid deposition

in patients with history of LLD

Madsen et al., Neurobiology of aging , 2012 Wu et al. Eur J Nucl Med Mol Imaging. 2014

Jack et al., Lancet Neurol, 2010

? ?

“amyloid +”

and LLD?

Amyloid deposition &

hippocampal volume in LLD

De Winter et al., In preparation

General principles

• Start with structural imaging, preferably MRI

• SPECT / PET only when diagnostic uncertainty

• Added value ~ diagnostic uncertainty (= old age

psychiatry)

• A ‘negative scan’ is clinically as important as a

positive scan (neg pred value!)

• Common sense: exploration cognitive deficit in a 95-

year old patient in a geriatric ward ≠ 60-year old pt in

memory clinic)

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General principles when interpreting scans• Look at scans! The more scans you see, the more

you will recognize

• Look at all slices, scroll through the scan

• Compare left/right, anterior/posterior, search for

asymmetries within patient

• Look for specific changes (hippocampal atrophy,

vascular damage, hypometabolism post cing, …)

• Discuss with radiologist/ nuclear medicine when

you are in doubt

• Experience will pay out!

• Large changes sensitize for small changes (general

principle in medicine)

Neuroimaging in practice