Differential Diagnosis of Dementia Flashcards
What is the work-up in suspected dementia?
- Suspicion of dementia
- Rule out metabolic/pscyhiatric causes
- Structural imaging
- CT prefered - pacemaker, claustrophobia, very old age
- MR prefered - young age, rapid progression
- If negative, consider SPECT/PET
What can psychiatric disorder present with?
Cognitive decline or alterations in personality which is due to neurodegeneration
Why should structural imaging be performed once?
To rule out whether the patient has a tumour or hydrocephalus or haematoma compressing the brain tissue
What is CT used to rule out?
Sub-dural haemotoma
What is observed in CADASIL?
Anterior temporal lesions
What can the atrophy pattern be?
- Focal
2. Generalised
What brain region is involved in Alzheimer’s or PSP?
- Alzheimer’s = medial temporal lobe
2. PSP = mesencephalon
What is the routine MRI protocol?
3D T1-weighted images (+ cor MPR)
– evaluation of the medial temporal lobe (MTA)
• axial FLAIR & T2 TSE
– hypoxic/ischaemic (white matter) pathology
• axial T2* gradient-echo (or SWI)
– detection of micro-bleeds and calcification
• DWI (Creutzfeld-Jacob)
What is the structural reporting for MRI?
- Swelling
- Infection, paraneoplastic - Primary GM loss
- AD, FTD, Parkinsonian syndromes - Vascular pathology
- Infarcts, lacunes, WMC (CAA, CADASIL) - Primary WM disease
- Leukodystrophies, MS, FXTAS
What is FLAIR and T2 used to look for?
Anything white in the brain, e.g. signal lesions due to ischaemia, dystrophy
What is T2* gradient echo used to look at?
Siderosis
What is DWI used to pick up?
Silent ischaemia
What is the structured reporting - swelling?
- Neoplastic
- gliomatosis cerebri, intravascular lymphoma - Autoimmune Limbic Encphalitis
- paraneoplastic, Hashimoto, VGKC, anti-NMDA - Infections:
- PML, herpes - NPH (rarely shunt-responsive)
- Vascilar
- dural AVF, AVM - RPLS/PRES
What is the structured reporting - primary WM?
Infectious – HIV, Whipple, syphilis • Inflammatory – MS, sarcoid, coeliac disease • Leukodystrophy – mitochondrial, peroxisomal – FXTAS, vanishing white matter (VWM) – adult polyglucogan body disease • Toxic/metabolic – CO, vitamin B, heroin – delayed post-hypoxic demyelination • Trauma
What is typical of CJD?
DWI has multi-focal areas of high signal in the cortex
Where is the pathology found in other patients with CJD?
- Stratium
- Putamen
- Caudate
- Sometimes in the thalamus
What is the structured reporting - primary GM
Alzheimer – mediotemporal, posterior variant • FTD – semantic, aphasic, frontal, right-temporal • Parkinsonian – DLB, PSP, MSA • Other movement disorders – Huntington, NBIA, Wilson • Prion disease – CJD, FFI, GSS
What brain regions do PSP and MSA affect?
- PSP = midbrain
2. MSA = pons
What does plaques formation interfere with?
Functioning of the synapses
What happens in the early stage of AD?
Tau is stained in the hippocampus especially in the entorhinal cortex
What does parahippocampal gyrus provide?
Input to the hippocampus
What can be observed on imaging for AD?
Tissue loss by hippocampi getting smaller and the surrounding spaces widening
What can you infer tissue loss from?
Expansion of CSF spaces
What can be observed on PET scan?
Abnormal protein accumulation
When do you see abnormal pattern?
Do not see the distinction between white and grey matter
What do modern scanners have?
Multiple detectors - very thin slices in a matter of seconds and reconstruct in a different plane
What is medial temporal lobe atrophy (MTA) score of 1 a landmark of?
Help identify where the hippocampus is 09
What is the MTA?
- < 75 years score > 1.5 abnormal
2. > 75 years score > 2 abnormal
What is visual rating - issues?
Advantage: quick and accessible – online and printed references • Depending on scan protocol – coronal plane, high-contrast T1 • Training of radiologists – ECNR, Erasmus, ESNR, ECR, etc. – interpretation: confounding, bias • Lack of subtlety – need finer grain / more steps in scale
What is VBM?
o Where you register all of the brain to standard space and then compare the densities of grey matter in various regions in the brain
o Correlate the grey matter densities with the scores and when you use the MTA scale of 1-4 – get a very nice correlation with the hippocampus in finding the amount of atrophy
o It is very specific it doesn’t correspond with atrophy in other place
Hippocampal volume - automated
o Can calculate the volume of the hippocampus
o Segmentation
o Hippocampus has a volume of 3800 square mm
What are the unresolved issues for MTA?
• Implementation of volumetric analysis
– better understanding of impact by scan quality
– move from workstations to scanner console
• Visual analysis: training of radiologists
– from training to certification?
• Interpretation issues
– normative data not standardized / available
• Integration with other data
– MRI: vascular burden, other ND features (including AD)
– non-imaging: CSF, genetic, clinical
WHAT IS FTLD semantic?
o Affects the left temporal lobe
o Hippocampus is very atrophied – grade 4 if not 5
o Asymmetry – from posterior to anterior
o Differences in score of more than 1
o Present relatively late
What is Bilateral DD, other MR findings, clinical clues and additional tests ?
- DD = AD, Hippocampal sclerosis, FTLD
- MR findings: Temporo-parietal atrophy, isolated finding, temporal pole or frontal atrophy, diffuse cortical atrophy
- clinical cluues = episodic memory loss, behavioural, language
- Additional tests = CSF, FDG, PIB
FDG - frontal hypoperfusion
Dopamine PET/SPECT
What is Unilateral DD, other MR findings, clinical clues and additional tests ?
- DD = FTLD, Mesial temporal sclerosis
- MR findings = Anterior more than frontal, temporal pole, frontal lobe atrophy
High signal hippocampus - Clinical clues = Behavioural, language, Epilepsy
- Additional tests = FDG frontal hypoperfusion
EEG
What is the patterns of atrophy in Alzheimers?
• Medio-temporal
– Hippocampus, parahippocampus
– APOE-4 positive, senile age, memory
• Posterior pattern
– posterior cingulate, interparietal sulcus
– APOE-4 negative, presenile, visuo-spatial
• Atypical patterns
– frontal or occipital predominance (Benton)
– behavioral or visual symptoms
• DD with FTLD and DLB
What is the MRI findings, clinical clues and additional test for AD?
- MRI findings: symmetrical (usually) biparietal atrophy (+/- occipital); hippocampal atrophy relatively late feature
- Clinical clues: Memory not completely normal, visuospatial deficits
- Additional tests: CSF, PIB
What is the MRI findings, clinical clues and additional test for DLB?
- MRI findings: generalised atrophy, parietal and occipital
- Clinical clues: extrapyramidal signs, hallucinations, fluctuations
- Additional test: Dopamine imaging
What is the MRI findings, clinical clues and additional test for CBD?
- MRI findings: Aysmmetric parietal (and frontal) atrophy
- Clinical clues: asymmetrical limb praxis, myoclonus
- Additional test: Dopamine imaging, FDG-PET
What is the MRI findings, clinical clues and additional test for CJD?
- MRI findings: FLAIR and DWI abnormal - cortical ribbon or stratium. May have generalised cerebral and cerebellar atrophy
- Clinical clues: Rapid decline, myoclonus
- Additional test: EEG (may be normal), CSF (tau&14-3-3)
What is the MRI findings, clinical clues and additional test for cerebrovascular?
- MRI findings: FLAIR/T2 signal change, watershed distribution
- Clinical clues: subcortical clinical features; stroke
- Additional: vascular risk factors
What is the structured reporting - vascular?
Small vessel disease – extensive WML, multiple lacunes – specific diseases: CADASIL, CAA • Large vessel pathology – strategic infracts, dominant hemisphere • Systemic causes of ischemia – vasulitis – mitochondrial – post-hypoxic demyelination
What is vascular disease and dementia?
combination of infarcts & AD best predicts dementia
(Nun & MRC-CFAS studies)
– “double hit” concept
• WML stepping stone for clinical AD
– subclinical damage lowers threshold
• atherosclerosis accelerates AD pathology
• amyloid deposits in vessels & parenchyma
– lobar microbleeds in CAA and AD
– central MBs in hypertension
What medications is used for MTA and severe WMH?
- MTA = cholinesterase inhibitors
2. Severe WMH = antihypertensive treatment
What is ARIA?
Amyloid Related Imaging Abnormalities
What is the take home points?
Exclude structural lesions – WM disease and swelling • Neurodegeneration – AD signature – medio-temporal OR posterior cingulate • Differential atrophy patterns – FTD, PSP, MSA (DLB) • VaD of vascular co-morbidity? – separate target for Rx • Functional PET/MRI techniques – bridge gap between amyloid & atrophy
