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Dementia - Atypicals
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Tony Bayer
DPM, School of Medicine,
Cardiff University
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Overview
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• Diagnostic criteria
• Red flags
• Brief cognitive assessment and imaging
• Atypical presentations
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ICD-10 – Diagnostic criteria for dementia
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Both of the following
• Decline in memory
• Decline in other cognitive abilities
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Absence of clouding of consciousness
Decline in emotional control, motivation, or social
behaviour
• Emotional lability
• Irritability
• Apathy
• Coarsening of social behaviour
Symptoms present for at least 6 months
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DSM-5 – Major cognitive disorder
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• Dementia subsumed under “Major
neurocognitive disorder”
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• evidence of significant cognitive decline from a
previous level of performance in one or more
cognitive domains (complex attention, executive
skills, learning and memory, language, perceptualmotor, or social cognition)
• cognitive deficits interfere with independence in ADL
(key distinction between mild and major NCD).
• cognitive deficits not attributable to another mental
disorder.
• NCD likely to be adopted by ICD-11 (due in 2017)
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Alzheimer’s disease
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• Insidious onset and gradual progression of
memory impairment in old age
• Gradual involvement of other cognitive
domains, such as language, construction and
abstraction
• Functional and social skills gradually impaired
• CNS examination normal until late in disease,
with some motor slowing
• Terminally bed-bound, with mutism and
paraplegia-in-flexion
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“A peculiar disease of the cerebral cortex”
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Alzheimer A. Allegmeine Zeitschrift fur Psychiatrie 1907; 64: 146-8.
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The first symptom was suspicion of her
husband ….. She dragged objects
here and there and hid them ….
Sometimes she greets her doctor as if
he were a visitor… At times she …
drags her bedding around, calls for
her husband or daughter …. Often
she screams for many hours in a
horrible voice
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International Working Group (IWG) criteria for typical
and atypical Alzheimer’s disease
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Dubois et al, Lancet Neurol 2014; 13: 614-29
B In-vivo evidence of Alzheimer’s pathology (one of the following)
Typical AD
• Decreased Aβ1–42 together with increased T-tau or P-tau in CSF
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A Specific clinical phenotype (one of the following)
• Early and significant episodic memory impairment, with gradual and
progressive change
Atypical AD
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• Posterior variant of AD defined by early, predominant, and progressive
impairment of visuoperceptive functions or visuospatial function
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• Logopenic variant of AD defined by early, predominant, and progressive
impairment of single word retrieval and repetition of sentences, in the
context of spared semantic, syntactic, and motor speech abilities
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• Frontal variant of AD defined early, predominant, and progressive
behavioural changes including apathy or behavioural disinhibition, or
predominant executive dysfunction on cognitive testing
• Down’s syndrome variant of AD defined early behavioural changes and
executive dysfunction in people with Down’s syndrome
• Increased tracer retention on amyloid PET
• AD autosomal dominant mutation present (in PSEN1, PSEN2, or APP)
Exclusion criteria (requiring blood tests & neuroimaging)
• History: sudden onset &/or early occurrence of gait disturbances,
seizures
• Clinical features: focal neurological features, early extrapyramidal signs,
early hallucinations, cognitive fluctuations
• Other medical conditions sufficient to account for memory and related
symptoms: non-AD dementia, major depression, cerebrovascular
disease, toxic, inflammatory, and metabolic disorders
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Distribution of dementia diagnoses
PDD
2%
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DLB
4%
FTD
2%
Pathological series
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Textbooks
Other
3%
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Mixed
10%
VaD
17%
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AD
62%
Vasc+some AD
16%
AD+someVaD
16%
Vasc only
11%
Other(often with
AD or Vasc)
4%
LB only
4%
AD+someLB
13%
AD
36%
Think about …
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Features suggesting atypical Alzheimer’s
or non-Alzheimer dementia
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• Onset and course
• Cognitive profile
• Presence of psychiatric and behavioural
symptoms at time of presentation
• Accompanying neurological symptoms
and signs
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Onset and course of dementia
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Features suggesting atypical Alzheimer’s
or non-Alzheimer dementia
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• More usual in middle aged/young
old
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• Sudden rather than insidious course
(Post-stroke, CAA)
• Significant cognitive fluctuations
(DLB)
• Subacute or rapidly progressive
course (CJD, infection, autoimmune,
neoplastic)
Non-amnestic presentation of
AD occurs in ~30% of EOAD &
5% of LOAD
(El Koedam et al, 2010)
Other
25%
AD
31%
DLB
4%
Alcohol
12%
FTD
13%
VaD
15%
Dementia diagnoses in under 65s
(Sampson et al, 2004)
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Features suggesting atypical Alzheimer’s
or non-Alzheimer dementia
Memory not dominant cognitive deficit
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• Language
• Visuospatial and perceptual skills
• Attention and executive abilities (subcortical)
AMT
MMSE
MoCA
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Memory
Episodic
ACE111
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Clock
+++
Semantic
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+
+
+
Remote
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+
-
-
Orientation
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++
+++
++
+++
Language
-
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+
++
+++
++
-
+
++
+++
Executive
+
-
-
++
++
Attention
+
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Equipment
+
-
+
-
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Time(min)
2
6
8
12
15
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Spatial
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Brief cognitive assessments
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Dementia presenting with language deficits
(primary progressive aphasia/PPA)
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Semantic dementia : PPA-S
Logopenic (phonological) : PPA-L
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• Problems with word order and
word production; know what
they want to say but can’t get it
out
• Usually tau pathology
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Non-fluent/agrammatic
aphasia : PPA-G
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• Problems with word recognition/
understanding; empty but fluent
speech
• Usually TDP-43 pathology
• Problems with word finding;
anomia, mispronunciations,
slow hesitant speech
• Usually amyloid pathology
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• Typically presents as visual
difficulties, problems
reading, driving, walking
into door frames, judging
distances (escalators),
telling time
• Often initially dismissed as
anxiety
• Nearly always Alzheimer
pathology
Dementia with Lewy Bodies
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Posterior cortical atrophy
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Dementia presenting with
visuospatial/perceptual deficits
• Visual hallucinations
• Disproportionate problems
with visuo-constructive tasks
• Positive DatScan
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• Subcortical ischaemic
vascular dementia (SIVD)
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Executive/
Dementia presenting with executive deficits
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• Parkinson’s Plus (DLB, PSP,
CBD)
• Frontotemporal dementia
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• Normal pressure
hydrocephalus
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• Alzheimer’s disease
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• Huntington’s disease
• HIV-D/HAND
Executive deficits imply
damage to frontal lobes or
extra-frontal neural circuits…
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Verbal fluency (animals, F words)
Backward digit span
Proverbs
Similarities (orange-apple)
Go-no-go tasks/sequencing
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Take home messages…
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Rarer dementias usually present in 50s and 60s – in older ages, atypical
presentations often reflect mixed pathology
Presenting symptoms reflect localization – not underlying pathology.
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Total score on cognitive testing is only half the story – always look at performance
on individual questions and map to relevant brain areas
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Don’t just rely on neuroimaging report – have a look yourself and discuss with
radiologist
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CSF examination (amyloid/tau), functional scans (SPECT/PET) and amyloid/tau
scans likely to be more routine in future – start getting to grips with them now