SUPPLEMENTARY INFORMATIONIn format provided by Elahi and Miller (doi:10.1038/nrneurol.2017.96)
Supplementary information S1 (box) | Diagnostic criteria for selected dementia syndromes
The diagnostic criteria for five frontotemporal dementia (FTD) syndromes (bvFTD, nfvPPA, svPPA, CBS and PSP), one atypical Alzheimer disease (AD) syndrome (lvPPA) and two Lewy body dementias (DLB and PDD) are listed below.
(A) Behavioural variant FTD (bvFTD)1
I. Possible bvFTD: progressive deterioration of behaviour and/or cognition (at least three of the following criteria)
(1) Early behavioural disinhibition
(2) Early apathy/inertia
(3) Early loss of sympathy/empathy
(4) Early perseverative, stereotyped or compulsive/ritualistic behaviour
(5) Hyperorality and/or dietary changes
(6) Neuropsychiatric test must show deficits in executive task + relative sparing of episodic memory + relative sparing of visuospatial skills
II. Probable bvFTD
Possible bvFTD + caregiver report of functional decline + positive topographical biomarkers of atrophy, hypometabolism, or hypoperfusion in frontal and anterior temporal lobes, via MRI/CT, PET andsingle-photon emission CT (SPECT), respectively.
III. Definite bvFTD
Possible bvFTD + post-mortem evidence of frontotemporal lobar degeneration (FTLD)-tau, FTLD-TDP or FTLD-FUS on autopsy OR presence of pathogenic mutation in C9orf72, GRN, TARDBP or VCP.
Exclusion criteria
Must be negative for possible and probable bvFTD:
(1) Evidence in support of nondegenerative aetiology
(2) Behavioural disturbance is better accounted for by a psychiatric diagnosis
Must be negative for probable bvFTD:
(3) Biomarkers strongly indicative of AD or other neurodegenerative process
(B) Primary progressive aphasia (PPA)2
All PPA syndromes
Must have all ofcriteria 1–3 and none of criteria 4–7:
Inclusion criteria
(1) Most prominent clinical feature is difficulty with language
(2) These deficits are the principal cause of impaired activities of daily living
(3) Aphasia should be the most prominent deficit at symptom onset and for the initial phase of the disease
Exclusion criteria
(1) Cognitive disturbance is better accounted for by a psychiatric diagnosis
(2) Prominent initial episodic and/or visual memory deficits, and visuoperceptual impairment (rule out AD)
(3) Prominent initial behavioural disturbance (rule out bvFTD)
Pathological diagnosis requires clinical diagnosis above plus either of the following:
(1) Histopathological evidence of anyneurodegenerative pathology: e.g. FTLD-tau, FTLD-TDP or AD, and/or
(2) Presence of a known pathogenic mutation
Nonfluent/agrammatic variant PPA (nfvPPA)
Must fulfilone or bothof criteria 1 and 2, and at least two of criteria 3–5:
(1) Agrammatism in language production
(2) Apraxia of speech
(3) Impaired comprehension of syntactically complex sentences
(4) Spared single-word comprehension
(5) Spared object knowledge
Imaging supportive of nfvPPA
(1) Predominant left posterior frontoinsular atrophy on MRI or
(2) Predominant left posterior frontoinsular hypoperfusion or hypometabolism on SPECT and PET
Semantic variant PPA (svPPA)
Must fulfilcriteria 1 and 2 and at least three of criteria 3–6:
(1) Impaired confrontation naming
(2) Impaired single-word comprehension
(3) Impaired object knowledge, particularly for low-frequency or low- familiarity items
(4) Surface dyslexia or dysgraphia
(5) Spared repetition
(6) Spared speech production (grammar and motor speech)
Imaging supportive of svPPA
Requires clinical diagnosis above plus one of following:
(1) Predominant anterior temporal lobe atrophy
(2) Predominant anterior temporal hypoperfusion or hypometabolism on SPECT or PET
Logopenic variant PPA (lvPPA)
Must fulfilcriteria 1 and 2 and at least three of criteria 3–6
(1) Impaired single-word retrieval in spontaneous speech and naming
(2) Impaired repetition of sentences and phrases
(3) Speech (phonological) errors in spontaneous speech and naming
(4) Spared single-word comprehension and object knowledge
(5) Spared motor speech
(6) Absence of frank agrammatism
Imaging supportive of lvPPA
(1) Predominant left posterior perisylvian or parietal atrophy on MRI, or
(2) Predominant left posterior perisylvian or parietal hypoperfusion or hypometabolism on SPECT or PET, respectively
(C.1) Corticobasal syndrome (CBS)3
Note: for CBS diagnostic criteria are not specific to the 4R FTLD-tau pathology of corticobasal degeneration (CBD)
I. Possible CBS:
Presentation may be symmetrical. Must have at least one of criteria 1–3 and one of criteria 4–6 below.
II. Probable CBS
Must have asymmetric presentation and at least two of criteria 1–3 and two of criteria 4–6:
(1) Limb rigidity or akinesia
(2) Limb dystonia
(3) Limb myoclonus
(4) Orobuccal or limb apraxia
(5) Cortical sensory deficit
(6) Alien limb phenomena
(C.2)Corticobasal degeneration (CBD)
I. Possible sporadic CBD:
Must have each of the following:
(1) Presentation with insidious onset and gradual progression
(2) Minimum 1-year duration of symptoms
(3) Permitted phenotypes are (a) possible CBS, (b) FBS, (c) nfvPPA, or (d) progressive supranuclear palsy syndrome (PSP-S) plus at least one CBS feature (1–6 above)
No Exclusion criteria
II. Probable sporadic CBD
Must have each of the following:
(1) Presentation with insidious onset and gradual progression
(2)1-year minimum duration of symptoms
(3) Age ≥50 years at onset
(4) Permitted phenotypes are probable CBS (above), or at least one CBS feature (1–6 above), in addition to frontal–behavioural subtype (FBS)3 or nfvPPA symptoms
Exclusion criteria
(1) Family history: two or more affected relativesand/ora genetic mutation affecting tau (e. g.MAPT mutation)
(2) Evidence of positive biomarkers for other neurodegenerative diseases (e.g. AD)
(3) Structural lesion suggestive of a focal cause
(4)FUS, GRN or TARDBP mutations or reduced plasma progranulin levels
III.Definite pathological criteria
(1) Tau-immunoreactive lesions in neurons and glia, particularly astrocytic plaques and thread-like lesions in both white and grey matter, in conjunction with neuronal loss in focal cortical regions and substantia nigra
(2) Supportive features: (a) ballooned cortical neurons, (b) cortical atrophy, and (c) tau-positive oligodendroglial coiled bodies
(D) Progressive supranuclear palsy syndrome (PSP-S)4
Inclusion criteria:
(1) Sporadic occurrence
(2) Age 40 years or older at onset
(3) Gradual progression
I. Possible PSP-S phenotypic subtypes:
(a) PSP Richardson syndrome
(1) Slow velocity of vertical saccades
(2) At least 3 steps backward on the pull-test within first 3 years
(b) PSP with predominant ocular motor dysfunction:
(1) Vertical supranuclear gaze palsy
(c) PSP with progressive gait freezing:
(1) Progressive gait freezing within 3 years
(d) PSP with predominant speech/language disorder:
(1)Vertical supranuclear gaze palsy, OR slow velocity of vertical saccades
(2)Nonfluent/agrammatic variant PPA, OR progressive apraxia of speech
(c)PSP with corticobasal syndrome:
(1)Vertical supranuclear gaze palsy, OR slow velocity of vertical saccades
(2) Cortical signs: orobuccal or limb apraxia, cortical sensory deficit, or alien limb phenomena
(3) Movement disorder: limb rigidity, akinesia, or myoclonus
II. ProbablePSP-S
(1) Vertical supranuclear gaze palsy, OR slow velocity of vertical saccades
(2) Second criteria defined by the PSP-S phenotypic subtypes:
(a) PSP Richardson syndrome
(1) Repeated unprovoked falls within 3 years or
(2) Tendency to fall on the pull-test within 3 years
(b) PSP with progressive gait freezing:
(1) Progressive gait freezing within 3 years
(c) PSP with predominant parkinsonism:
(1) Parkinsonism, akinetic-rigid, predominantly axial and levodopa resistant
(d) PSP with predominant frontal lobe presentation: at least 3 among
(1) Apathy
(2) Bradyphrenia
(3) Dysexecutive syndrome
(4) Reduced phonemic verbal fluency
(5) Impulsivity, disinhibition or perseveration
PSP supportive diagnostic features
Clinical
(1) Levodoparesistance
(2) Hypokinetic, spastic dysarthria
(3) Dysphagia
(4) Photophobia (attributed to adaptative dysfunction)
Neuroimaging
(1) Predominant midbrain atrophy or hypometabolism
(2) Postsynaptic striatal dopaminergic degeneration
Exclusion criteria
(1) Predominant impairment of episodic memory, suggestive of AD
(2) Predominant autonomic failure
(3) Predominant visual hallucinations or fluctuations in alertness
(4) Predominant multisegmental upper and lower motor neuron signs
(5) Sudden onset, step-wise, or rapid progression
(6) Gradual progression
(7) Prominent appendicular ataxia
(8) Other identifiable causes of postural instability
(9) History of encephalitis
(10) Imaging consistent with diagnosis of leukoencephalopathy
(11) Imaging suggestive ofnormal pressure hydrocephalus (NPH), lesions in basal ganglia, diencephalon or brainstem
(E) Dementia with Lewy bodies (DLB)5
Central features
(1) Dementia, defined as progressive cognitive decline of sufficient magnitude to interfere with normal social or occupational function
(2) Prominent or persistent memory impairment—not necessarily occurring in the early stages but evident with progression
(3) Deficits may be especially prominent in testing of attention, executive function and visuospatial ability
Core features
(1) Fluctuating cognition with pronounced variations in attention and alertness
(2) Recurrent visual hallucinations that are typically well formed and detailed
(3) Spontaneous features of parkinsonism
Suggestive features
(1) REM sleep behaviour disorder
(2) Severe neuroleptic sensitivity
(3) Low dopamine transporter uptake in basal ganglia (based on SPECT or PET)
I.Possible DLB:
(1) Central diagnostic feature
(2) 1 core feature OR ≥1 suggestive features
II. Probable DLB:
(1) Central diagnostic feature
(2) ≥2 core features OR 1 core features and ≥1 suggestive features
(F) Parkinson disease dementia (PDD)6
I. Possible PDD:
(1)Prior diagnosis of PD
(2)Dementia with deficit in ≥2 cognitive domains, including at least one domain with atypical profile
(3)Possibility of 1 feature that may make the diagnosis uncertain
II. Probable PDD:
(1)Prior diagnosis of PD according to Queen Square Brain Bank criteria
(2)Dementia with deficit in ≥2 cognitive domains with typical profile
(3)Absence of features that may make the diagnosis uncertain
Typical profile of affected cognitive domains
(1) Attention: impairment may fluctuate during the day and from day to day
(2) Executive function: impairment especially in tasks requiring initiation, planning, concept formation, rule finding, set shifting or set maintenance; as well as impaired mental speed (bradyphrenia)
(3) Visuospatial functions: impairment in tasks requiring visuospatial orientation, perception, or construction
(4) Memory: impairment in free recall of recent events or in tasks requiring new learning; improvement with cueing, and recognition better than free recall
(5) Language: word finding difficulties and impaired comprehension of complex sentences with relative preservation of core functions
Behavioural symptoms (supportive features)
(1) Apathy: decreased spontaneity, motivation, interest, and effortful behaviour
(2) Changes in personality and mood, including features of depression and anxiety
(3) Hallucinations (mostly visual), usually complex formed visions of people, animals or objects
(4) Delusions, typically paranoid, such as infidelity, or phantom boarder (e.g. unwelcome guests living in the home)
(5) Excessive daytime sleepiness
Features causing diagnostic uncertainty (not excluding criteria)
(1) Coexistence of abnormalities that can cause cognitive impairment, but judged not to be the cause of dementia, e.g. presence of vascular lesions in relevant territory on neuroimaging
(2) Time interval between the development of motor and cognitive symptoms not known
Exclusion criteria
(1) Cognitive or behavioural symptoms occurring only in the context of existing conditions such as acute confusion due to systemic diseases, drug intoxication, or major depression
(2) Symptoms compatible with vascular dementia, confirmed by an established relationship between brain imaging results and impairments noted on testing
References
1Rascovsky, K. et al. Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain134, 2456–2477 (2011).
2Gorno-Tempini, M. L. et al. Classification of primary progressive aphasia and its variants. Neurology76, 1006–1014 (2011).
3Armstrong, M. J. et al. Criteria for the diagnosis of corticobasal degeneration. Neurology80, 496–503 (2013).
4Höglinger, GU. et al.Clinical diagnosis of progressive supranuclear palsy: the Movement Disorder Society criteria. Mov. Disord.
5McKeith, I. G. et al.Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium. Neurology 65, 1863–1872 (2005).
6Emre, M. et al.Clinical diagnostic criteria for dementia associated with Parkinson’s disease. Mov. Disord. 22, 1689–1707 (2007).
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