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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
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Semantic
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Remote
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Orientation
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Language
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Executive
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Attention
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Equipment
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Time(min)
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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… • • • • •
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
