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1 Dementia - Atypicals Tony Bayer DPM, School of Medicine, Cardiff University
2 Overview Diagnostic criteria Red flags Brief cognitive assessment and imaging Atypical presentations
3 ICD-10 Diagnostic criteria for dementia Both of the following Decline in memory Decline in other cognitive abilities 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
4 DSM-5 Major cognitive disorder Dementia subsumed under Major neurocognitive disorder 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)
5 Alzheimer s disease 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
6 A peculiar disease of the cerebral cortex Alzheimer A. Allegmeine Zeitschrift fur Psychiatrie 1907; 64: 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
7 International Working Group (IWG) criteria for typical and atypical Alzheimer s disease Dubois et al, Lancet Neurol 2014; 13: A Specific clinical phenotype (one of the following) Typical AD Early and significant episodic memory impairment, with gradual and progressive change Atypical AD Posterior variant of AD defined by early, predominant, and progressive impairment of visuoperceptive functions or visuospatial function 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 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 B In-vivo evidence of Alzheimer s pathology (one of the following) Decreased Aβ1 42 together with increased T-tau or P-tau in CSF 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
8 Mixed 10% VaD 17% Distribution of dementia diagnoses DLB 4% FTD 2% Textbooks PDD 2% Other 3% AD 62% Vasc only 11% Other(often with AD or Vasc) 4% LB only 4% Pathological series Vasc+some AD 16% AD+someLB 13% AD+someVaD 16% AD 36%
9 Features suggesting atypical Alzheimer s or non-alzheimer dementia Think about Onset and course Cognitive profile Presence of psychiatric and behavioural symptoms at time of presentation Accompanying neurological symptoms and signs
10 Features suggesting atypical Alzheimer s or non-alzheimer dementia Onset and course of dementia More usual in middle aged/young old Sudden rather than insidious course (Post-stroke, CAA) Significant cognitive fluctuations (DLB) Subacute or rapidly progressive course (CJD, infection, autoimmune, neoplastic) DLB 4% Other 25% Alcohol 12% FTD 13% VaD 15% AD 31% Dementia diagnoses in under 65s (Sampson et al, 2004) Non-amnestic presentation of AD occurs in ~30% of EOAD & 5% of LOAD (El Koedam et al, 2010)
11 Features suggesting atypical Alzheimer s or non-alzheimer dementia Memory not dominant cognitive deficit Language Visuospatial and perceptual skills Attention and executive abilities (subcortical)
12 Memory Brief cognitive assessments Clock AMT MMSE MoCA ACE111 Episodic Semantic Remote Orientation Language Spatial Executive Attention Equipment Time(min)
13 Dementia presenting with language deficits (primary progressive aphasia/ppa) Non-fluent/agrammatic aphasia : PPA-G Problems with word order and word production; know what they want to say but can t get it out Usually tau pathology Semantic dementia : PPA-S Problems with word recognition/ understanding; empty but fluent speech Usually TDP-43 pathology Logopenic (phonological) : PPA-L Problems with word finding; anomia, mispronunciations, slow hesitant speech Usually amyloid pathology
14 Dementia presenting with visuospatial/perceptual deficits Posterior cortical atrophy 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 Visual hallucinations Disproportionate problems with visuo-constructive tasks Positive DatScan
15 Executive/ Dementia presenting with executive deficits Subcortical ischaemic vascular dementia (SIVD) Parkinson s Plus (DLB, PSP, CBD) Frontotemporal dementia Normal pressure hydrocephalus Alzheimer s disease 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
16 Take home messages Rarer dementias usually present in 50s and 60s in older ages, atypical presentations often reflect mixed pathology Presenting symptoms reflect localization not underlying pathology. Total score on cognitive testing is only half the story always look at performance on individual questions and map to relevant brain areas Don t just rely on neuroimaging report have a look yourself and discuss with radiologist 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
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