detail of scoring of atrophy with changes in degenerative dementia and some reversible causes...advance imaging also included.

1. Neuroimaging in
Dementia
DR BHAVIN J PATEL
SR NEUROLOGY
GOVT. MEDICAL COLLEGE, KOTA

2. Outline of seminar
Introduction
Types of imaging and its use
Normal aging
Primary grey matter disease
Vascular dementia
NPH
Disease primarily affecting white matter
Infections
Multiple sclerosis
Autoimmune encephalitis
Neoplasia
Vitamin B1 deficiency
leuckodystrophies

3. Introduction
Dementia is usually defined as an acquired condition involving multiple
cognitive impairments that are sufficient to interfere with activities of daily
living
35.6 million patient in 2010 world wide
6.4% patient of dementia, 4.4% of Alzheimer disease & 1.6% vascular
dementia
Diagnosis is critically dependent on careful history taking with clinical and
cognitive examination supported by ancillary investigations.

4. Neuroimaging in Dementia
Focus of imaging shifted from exclusionary
to inclusionary
Indications of neuroimaging in dementia:-
Early Diagnosis
 classification of sub type of dementia.
Extent of disease
To rule out treatable etiology.

5. Structural imaging
It includes CT scan and MRI.
CT Scan:-
To rule out surgically treatable cause
To look for vascular changes.
Assessment of atrophy.

6. MRI
Determine degree and pattern of general cortical atrophy(GCA)
Assess focal atrophy
Assess microbleeds.
Determine degree of vascular damage and occurrence of strategic
infarct
Differentiate between various etiology.
Exclude structural lesion.

7. MRI
3D T1 weighted:- assessment of atrophy
and volume measurement.
T2/FLAIR:- various pathological changes
in white matter can be seen.
For thalamic and posterior fossa lesion T2
is better.
T2 Gradient echo/SWI:-for microbleeds.

8. Microbleeds

9. Indications for DWI or contrast imaging

10. Visual rating scale
Global cortical atrophy scale:-
Best assessed on FLAIR or 3D T1 weighted images.

11. Medial temporal atrophy scale
< 75 years: score 2 or more is abnormal
 > 75 years: score 3 or more is abnormal

12. Koenam posterior/parietal atrophy scale

14. White matter rating scale

15. Advanced MR Techniques
Perfusion weighted imaging(PWI):-
Can be performed invasively by injecting a paramagnetic contrast bolus, or
non-invasively by applying a magnetic tag (arterial spin labelling or ASL)
Type of information obtained is comparable with nuclear medicine
E.g Temporo-parietal hypoperfusion in AD.

16. Advanced MR Techniques
MR spectroscopy:-
Measures the concentration of certain brain metabolites.
Specific abnormalities indicating a unique disease condition
Changes in the ratios of the normal metabolites
In patients with neurodegenerative disorders, the usual finding is a change
in the ratio between metabolites or a general decrease in metabolites
Loss of NAA in the basal ganglia may differentiate multisystem atrophy
(MSA) from idiopathic Parkinson’s disease

17. Advanced MR Techniques
BOLD fMRI :-
 fMRI typically refers to images obtained by using the blood oxygen-
level dependent (BOLD) contrast
 Difference in magnetic susceptibility between oxygenated and
deoxygenated blood serves as an intrinsic contrast medium
 It is non-invasive and not required radioactive contrast media

18. Advanced MR Techniques
DTI(diffusion tensor imaging):-
DTI in dementia have consistently shown altered diffusion (tract)
properties in accordance with the pattern of neurodegenerative pathology
By using DTI and fibre tracking, tract-specific pathology can be
demonstrated

19. SPECT and PET
Rely on the detection of radioactive signals from a labelled compound
(tracer) that selectively binds in the brain.

20. PET

21. SPECT

22. Normal ageing
In successful ageing, elderly subjects have apparently minimal
morphological (and probably physiological) loss relative to younger
individuals
In usual ageing, brain imaging abnormalities are present without
overt clinical deficits or symptoms; subtle cognitive deficits may be
detected with neuropsychological testing.

23. Normal ageing
Global cortical atrophy:-
Brain weight peaked by the mid-to-late teens.
0.2% / year:- 30-50 years
0.3 to 0.5%/ year:- 50-70 years
Shrinkage of cortical grey matter predominates over white matter loss
The parietal and frontal lobes are equally affected.

24. Normal ageing
Medial temporal atrophy:-
MTA score 2 is normal in nondemented pt over 75 year age.
0.2% per year:- 30-50 yr
0.8% per year:-50-70yr
1.5 to 2% per year:- above 80 yr
Microbleeds:-
Usually found in the basal ganglia or thalamus and posterior fossa in
hypertensive patients

25. Normal ageing
Enlarged Virchow robin space:-
Most enlarged VRS <2 mm in diameter
Usually found in striatum, ant perforated
substance and ant commissure
Diffuse widening of VRS in basal
ganglia is suggestive of focal atrophy

26. Normal ageing
White matter hyper intensities:-
Periventricular hyperintensities suggestive
of increase extracellular fluid and sub
ependymal gliosis.
Represent usual aging phenomenon.
Panctiform and early confluent deep
WMH often have little clinical
consequences.

27. Normal ageing
Iron accumulation:-
Usually involves globus pallidus ,
striatum, substantia niagra and dentate
nucleus
Hypointensity on T2 images
Started appearing around third decade

28. Normal ageing
Reduced resting-state fMRI activity (anterior frontal, precuneus, and
posterior cingulate cortices) in ageing.
Grey matter perfusion decreases by 0.45% per year in healthy adult subjects,
predominantly in the frontal cortex
Hypometabolism in frontal and post cingulate cortex on FDG-PET.
Abnormal uptake in amyloid-PET is seen in 30% normal eldery subjects.

29. Primary Grey Matter Dementia

30. Alzheimer disease
Also known as senile dementia of Alzheimer type.
Disease Named by kraepelin in 1914.
Sporadic (mc) or familial
Predominantly involve temporo-parietal lobe
Average survival is 8-13 years.

31. Alzheimer disease
Clinical presentation:-
Starts with deficit in episodic memory.
As disease progeress:-
Aphasia
Apraxia and agnosia
Executive dysfunction
Psychiatry and behavioral problem

32. Structural imaging
MRI is preferred over CT.
Focal atrophy in the medial temporal
region, including the hippocampus
Spreading from the entorhinal cortex and
hippocampus to the association cortices,
Decline in hippocampal volume is 2.5
times grater than normal individual.

33. Volumetric MRI scan

34. Differential diagnosis of Hippocampal atrophy

35. Structural imaging
Prominent posterior atrophy is prevalent
among younger AD patients and more
often in APOE4 non-carriers
58-year-old presented with cognitive
decline characterised by marked
visuospatial and praxis difficulties with
relatively preserved memory –

36. Differential diagnosis of parietal lobe atrophy

37. Structural imaging
Signs of small vessel disease are
present on MRI in the form of :-
White matter hyperintensities (WMH),
Lacunar infarcts (lacunes)
Microbleeds

38. PET
Sensitivity and Specificity in the range of 85–90%
FDG-PET temporoparietal hypometabolism.
The Pittsburgh compound B ([11C]PIB) is the most widely studied amyloid tracer in
AD patients
18F-labelled PIB or other compounds such as AV45 or Florbetaban
Amyloid deposition also occur in DLB and CAA.

39. PET
64 year old AD and
normal individual
amyloid –PET scan.

40. SPECT:-
99TC HMPAO scan shows hypoperfusion in temporo parietal area.
Neurorecepator scan- DAT scan helpful in differentiating DLB from AD.
MR spectroscopy:-
Shows mildly reduced NAA and increase myo-inositol.
Low NAA:Cr ratio in the posterior cingulate gyri and left occipital cortex
predicts conversion from MCI to probable AD

41. Frontotemporal Lobar Degeneration(FTLD)
Synonyms:- picks disease, frototemporal dementia
5-10% cases of dementia
Second cause of dementia after AD in younger patient.(45-65 yr)
a. Behavioural variant frontotemporal dementia (bvFTD)
b. Progressive nonfluent aphasia (PNFA)
c. Semantic dementia (SD)

42. Structural imaging
T1 weighted images:-
Atrophy of frontal and temporal lobes with relative sparing of parieto occipital lobe
Usually bilateral but asymmetric.
Earliest area of sulcal widening is probably the orbitofrontal cortex, followed by the
mesiofrontal (interhemispheric) cortex
Medial temporal lobe is more affected anteriorly (amygdala being more affected
than the hippocampus)

44. PNFA
Dominant (left) hemisphere
perisylvian regions, particularly the
left inferior frontal and insular
Cortices are affected early.
55 yr old female pt p/w difficulties in
expressive language.
Images range from asymptomatic
scan to 56 mth scan from symptoms.

45. Semantic dementia
Left temporal> right
Anterior > posterior
Inferior > superior
Knife edge or razor back atrophy.
Advance stage bilateral involvemnt

46. Right temporal lobe variant of FTLD:-
Rarely patient p/w right temporal atrophy
and symptom of prosopagnosia
.
Subsequently develop semantic dementia.

47. Other Imaging
FDG-PET and (HMPAO-)SPECT characteristically show frontal and
temporal hypoperfusion/hypometabolism with relative sparing of
parietal and occipital
MR spectroscopy shows lower NAA:Cr ratio and higher MI:Cr
ratio.

48. Dementia with Parkinsonism
Mainly two entities:-
Dementia with lewy body(DLB):- If parkinsonism precedes
dementia by <1 year, or follows the dementia
15 % cases of late onset dementia
Second most common cause of dementia after AD.

49. Dementia with Parkinsonism
Parkinson disease dementia (PDD):- If dementia develops >1 year after
parkinsonism
20-30% among PD patient
PDD and DLB share cognitive, neuropsychiatric, neurochemical, pathological
and imaging similarities
Fluctuation and visual hallucinations are slightly less frequent in PDD.

50. Structural imaging
Mild generalized atrophy with relative sparing of sensori-motor coertex.
Rate of atrophy lesser than AD.
Medial temporal atrophy can occur in severe and advanced disease
White matter hyperintensities on T2-weighted images are perhaps more severe in
DLB/PDD than healthy subjects

51. PET/SPECT
Show a similar pattern of hypometabolism/perfusion
in DLB and PDD particularly involving
 Occipital cortex,
 Midline and inferior parietal regions,
Lateral temporal cortex,
Inferior and medial frontal lobe
MR spectroscopy:-
Relative normal NAA and Myoinositol level.

52. Special PET
Dopaminergic system:-
123I labelled dopaminergic presynaptic ligand
FP-CIT
Uptake is almost absent in the putamen, and
reduced in the caudate.
Sensitivity ~75% and specificity of ~90% for
distinguishing PDD/DLB from non-DLB
dementia.
Amyloid imaging:-
Uptake is similar to AD.

53. Progressive supranuclear palsy
Also known as Richardson syndrome
Clinical presentation:-
Early backward fall
Mild symmetrical parkinsonism
Early ocular manifestation

54. Structural imaging
Mild generalized supratentorial atrophy
with occasional fontal predominance
The characteristic imaging features:-
 Midbrain atrophy,
Divergence of the red nuclei,
Dilatation of the third ventricle,
Atrophy of the superior cerebellar peduncle.
ADC value at MCP differentiate MSA
from PSP.
Humming bird or penguin signMickey mouse or morning
glory sign

55. Sup. Cerebellar peduncle
atrophy In PSP.
Hypometabolism in midbrain
and frontal lobe on PET.
Use of DTI and tractography are
in research.

56. Multi System Atrophy(MSA)
Diveded in three types:-
MSA-P :- Parkinsonian type
Neuronal loss and gliosis in substantia nigra, putamrn and caudate
MSA-C:- Cerebellar type
Neuronal loss occur in inf olivary nucleus, pons and cerebelleum.
MSA-A:- Autonomic failure
Dementia is usually not occur but cognitive decline can occur in advanced state.

57. Neuroimaging
T1 image shows predominant pons
and cerebellar atrophy.
Hot cross bun sign on T2 or
FLAIR.
Diffusion imaging:-
High ADC value in putamen in
MSA
Hypometabolism in pons and
cerebellum in PET.

58. Volumetri assessment
in MSA vs PSP.

59. DTI image of normal, MSA and PSP
MCP(yellow) SCP (purple)

60. Corticobasal Degeneration (CBD)
Usually present in 6 to 8 decade
Exact prevalence is not known.
Clinical presentation:-
Alien limb phenomenon
Gait disturbance and Asymmetric parkinsonism
Cognitive impairment.
 Behavioral and language impairment (rare)
Difficult to diagnose clinically.

61. Neuromaging
Less studied on imaging
Imaging can be normal in early
stage.
Asymmetric cortical atrophy
Asymmetric AD is more Common
than CBD.

62. Creutzfeldt-Jakob disease
Rapidly progressive neurodegenerative disease caused by proteinaceous
infectious particles.
 Four types of CJD are recognised: spoardic, familial, iatrogenic, variant.
It accounts for 90% of all prion diseases and approx. 85% of CJD cases are
sporadic

63. Creutzfeldt-Jakob disease
 MR with DWI is the imaging procedure of choice.
 T1 scans are normal.
 T2/FLAIR hyperintensity in the BG, thalami, and the cerebral cortex is the most
common initial abnormality in classic sCJD.
The anterior caudate and putamen are more affected than the globus pallidus.

64. Creutzfeldt-Jakob disease
 Cortical involvement is asymmetric.
 Occipital lobe involvement predominates in the heidenhain variant.
 Cerebellum is affected in the brownell-oppenheimer variant.
 T2/FLAIR hyperintensity in the posterior thalamus(pulvinar sign) or
posteromedial thalamus(hockey stick sign) is seen in 90% of vCJD cases
 Unlike most dementing diseases, CJD shows striking diffusion restriction.

65. Creutzfeldt-Jakob disease

66. Creutzfeldt-Jakob disease
Hockey stick sign Pulvinar sign

67. Vascular Dementia

68. Vascular dementia
Vascular dementia is second most common cause of dementia.
It can be divided in
Large vessel VaD
Small vessel VaD
Vasculitis dementia

69. Large vessel VaD:-
Multiple or single cortical–subcortical
cerebrovascular lesions involving strategic regions
of the brain.
T2 and FLAIR images are better for chronic
ischemic changes.
Hypointensity on T1:- complete infarct
MR/CT angiography or DSA useful to identified
occluded vessel.

70. Small vessel vascular dementia
Also known as atherosclerotic dementia or binswanger disease
More common than large vessel VaD
Brain lesion include:-
Cortical and subcortical lacunar infarct
Microbleeds.
Enlarged Virchow robin space
Diffuse white matter changes (incomplete infarction)
CADASIL can present as small VaD.

71. Neuroimaging
Ct showing diffuse hypodensity in white matter
referred as leuckorioasis.
White matter changes on MRI are visible as
diffuse hyperintense abnormalities on T2 and
FLAIR
No hypointensity on T1
Sparing of U fibers.
PWI perform to look for cerebrovascular
reserve and perfusion.

72. CAA
62 yr old female K/C/O DM
and IHD p/w forgetfulness.
Initial imaging was showing
white matter hyperintensities
with macroscopic bleed
consistent with CAA.
6 month latter presented with
posterior fossa bleed.

73. CADASIL vs small vessel disease
U fiber involvement
Temporal lobe
involvement
Ext capsule involvement
not specific
Normal MR angio
Lactate peak on MR
spectroscopy.

74. Mixed dementia
Over 75 year age mixed disease underlies
clinical syndrome of dementia
Two main pathology are:-
Neurodegenrative
cerebrovascular changes.
These pathologies may add up or aggravate
each other effect.

76. Normal Pressure Hydrocephalus (NPH)
NPH is thought to be due to a disturbance of CSF dynamics,
Clinical triad of symptoms
 Mental deterioration,
 Gait instability,
 Urinary incontinence

77. Neuroimaging
CT demonstrate hydrocephalus out of proportion to
atrophy
MRI findings:-
Upward bowing of the corpus callosum (sagittal)
 small CC angle (coronal)
Evans (frontal horns to inner table skull) index >0.3
Absence of sulcal widening and cortical atrophy
Small bands of trasependymal CSF flow can be present.
CSF flow can be quantified by phase contrast MRI.

79. White matter disease

80. Infections
HIV encephalopathy:-
Dementia occur in 25% of HIV patients
Insidious onset progressive cognitive impairment
Neuroimaging:-
Mild to moderate diffuse hyperintensity on
T2/FLAIR involving periventricular region
Isointense on T1
No contrast enhancement
Increase choline and myoinositol ,Decrease NAA

81. Progressive Multifocal
Leukoencephalopathy
PML is caused by the JC papovavirus,
Almost exclusively in immunocompromised
patients
 Infects oligodendrocytes and leads to massive
demyelination
Focal areas of hyperintensities on T2-weighted
Markedly hypointense on T1-weighted located
in the subcortical white matter, with gyral
Swelling
No contrast enhancement

82. HSV Encephalitis
Mc viral encephalitis.
Acute cognitive impairment
Neuroimaging:-
Bilateral asymmetrical hyperintensity
involving medial temporal lobe
Diffusion restriction in early phase
Hyperintense on T1 if Haemorrhage
Variable contrast enhancement.

83. Multiple sclerosis
25 yr old female pt p/w sudden onset memory and concentration deficit.

84. Autoimmune limbic encephalitis
Can be paraneoplastic or primary autoimmune
encephalitis
Subacute onset episodic memory impairment
Associated with behavioral abnormality and
seizure.
Neuroimaging:-
Circumscribed symmetrical bilateral medial
temporal lobe involvement
Less frequent enhancement on contrast
FDG-PET to rule out primary tumor

85. Vitamin B1 deficiency
Known as Wernicke’s encephalopathy and korsakoff syndrome
Common in alcoholics, post gastric surgery, hemodialysis and chemotherapy
Presented as
 Occulomotor abnormalities
 Cerebellar dysfunction
 Altered mental status/mild memory impairment

86. Vitamin B1 deficiency
T1:- occasional hyperintense due to
Microhaemorrhages
T2/FLAIR:- hyperintensity in characteristic
areas
–– Medial thalamus
–– Mamillary bodies
–– Periaqueductal GM and colliculi
 Contrast enhancement can be seen in
the acute phase
–– May be absent in non-alcohol WE
DWI :- restriction in acute phase of the
disease

87. Neoplasia
Brain tumors when present in following area can present as neuro cognitive
impairment.
Temporal lobe
Basal frontal area
Bilateral thalamus
Corpus callosum
In slow growing tumors symptoms can appear before radiological signs.

88. Gliomatosis cerebri
CT can be normal as isodense lesion
MRI:-
T1:- Iso to hypointense
T2:- hyperintense
T1 contrast:- No to minimal contrast
enhancement
DWI:- no restriction
MRS:- elevated Cho:Cr and Cho:NAA ratios
FDG-PET:- marked hypometabolism

89. Lymphoma
CT shows hyperdense lesion
MRI:-
T1:- hypointense to grey matter
T2:-variable, hyperintense (45%)
isointense(35%)
T1 Contrast:-high grade tumor shows intense
homogenous enhancement
DWI:-restricted diffusion with low ADC
value
MRS:- choline peak ,Decrease NAA, Reverse
Choline/Cr ratio.

90. Mitochondrial dementia
Cause by acquired or inherited respiratory gene
mutations.
Multisystem involvement
Cerebral involvement can present with
psychiatry or cognitive symptoms.
Plain CT may show calcification.
Hyperintense lesion on T2 and FLAIR
involving deep grey matter and cortex.
Acute lesion shows diffusion restriction.
Persistent lactate peak on MRS.
60 yr old previously healthy male p/w cognitive impairment.

91. Adult onset polyglucosan
body disease
Characterized by accumulation of
carbohydrate inclusion body
Symptom appear in 5-6th decade.
Non enhancing confluent symmetrical
periventricular hyperintense lesion on T2
Sparing of U fiber
Temporal lobe white matter involvement
Lactate peak with decrease NAA on MRS

92. Late onset metachromatic
leuckodystropy
AR lysozomal storage disease
Demyelination of white matter with accumulation of
sulphatidies
In adult p/w psychiatry symptoms and memory impairment
T1: affected areas are low signal
T1 C+ (Gd):- no enhancement is characteristic
multiple cranial nerve enhancement has been reported
T2: affected areas are high signal and may show a "tigroid
pattern on axial plane
DWI:- diffusion restriction occasionaly
MR spectroscopy: - reduced N-acetylaspartate
◦ increased myo-inositol and lactate

93. Vanishing white matter
disease
In adult present as seizure with pshychiatry
symptoms and dementia
Neuroimaging:-
Diffuse periventricular hyperintensity on T2
and FLAIR.
Over time white matter vanish and shows
central hypointensity similar to csf.
Variable cerebellar atropy.
MRS shows only lactate and glucose peak.

94. Adrenomyeloneuropathy
Adult form of X-linked ALD
3rd to 4th decade with Progresasive paraparesis,
neuropathy and cerebellar ataxia
50% pt had cognitive dysfunction
MC location:- parieto occipital DWM and corpus
callosum
T1:- hypointense central zone
T1 C+ (Gd):- enhancement is seen in around 50%
Serpiginous enhancement visible in the anteriormost
periphery of the lesions
T2:- central zone: markedly hyperintense
peripheral zone: moderately hypointense

95. References
Bradely’s neurology in clinical practice, 7th edition
Text book of neuroimaging in dementia ,Frederick burkhof, Nickfox.
Neuroimaging in Dementia The Journal of the American Society for Experimental
Neurotherapeutics, volume 8, 82-92, jan 2011
Neuroimaging in Dementia Adam M. Staffaroni ,Semin Neurol. 2017 October ;
37(5): 510–537
uptodate.com
Radiopedia.com

96. Thank You