Criteria

A number of classification systems have been developed for the diagnosis of frontotemporal dementia (FTD). Widely used criteria are described in detail here.

International consensus criteria for behavioural variant FTD[7]

In 2011, an international consortium developed guidelines for the diagnosis of behavioural variant FTD (bvFTD). These criteria show encouragingly high sensitivity and specificity when applied to patients with early-onset dementia and provide a useful tool both for specialist researchers and for general clinicians.[7][8][9]​​​

I. Neurodegenerative disease

The following symptom must be present to meet criteria for bvFTD:

  • A. Shows progressive deterioration of behaviour and/or cognition by observation or history (as provided by a knowledgeable informant).

II. Possible bvFTD

Three of the following behavioural/cognitive symptoms (A-F) must be present to meet criteria. Ascertainment requires that symptoms be persistent or recurrent, rather than single or rare events.

  • A. Early* behavioural disinhibition (one of the following symptoms [A.1-A.3] must be present):

    • A.1. Socially inappropriate behaviour

    • A.2. Loss of manners or decorum

    • A.3. Impulsive, rash, or careless actions

  • B. Early apathy or inertia (one of the following symptoms [B.1-B.2] must be present):

    • B.1. Apathy

    • B.2. Inertia

  • C. Early loss of sympathy or empathy (one of the following symptoms [C.1-C.2] must be present):

    • C.1. Diminished response to other people’s needs and feelings

    • C.2. Diminished social interest, interrelatedness, or personal warmth

  • D. Early perseverative, stereotyped, or compulsive/ritualistic behaviour (one of the following symptoms [D.1-D.3] must be present):

    • D.1. Simple repetitive movements

    • D.2. Complex, compulsive, or ritualistic behaviours

    • D.3. Stereotypy of speech

  • E. Hyper-orality and dietary changes (one of the following symptoms [E.1-E.3] must be present):

    • E.1. Altered food preferences

    • E.2. Binge eating, increased consumption of alcohol or cigarettes

    • E.3. Oral exploration or consumption of inedible objects

  • F. Neuropsychological profile: executive/generation deficits with relative sparing of memory and visuospatial functions (all of the following symptoms [F.1-F.3] must be present):

    • F.1. Deficits in executive tasks

    • F.2. Relative sparing of episodic memory

    • F.3. Relative sparing of visuospatial skills.

III. Probable bvFTD

All of the following symptoms (A-C) must be present to meet criteria.

  • A. Meets criteria for possible bvFTD

  • B. Exhibits significant functional decline (by carer report or as evidenced by Clinical Dementia Rating Scale or Functional Activities Questionnaire scores)

  • C. Imaging results consistent with bvFTD (one of the following [C.1-C.2] must be present):

    • C.1. Frontal and/or anterior temporal atrophy on MRI or CT

    • C.2. Frontal and/or anterior temporal hypoperfusion or hypometabolism on PET or single-photon emission computerised tomography.

IV. Behavioural variant FTD with definite frontotemporal lobe degeneration (FTLD) pathology

Criterion A and either criterion B or C must be present to meet criteria

  • A. Meets criteria for possible or probable bvFTD

  • B. Histopathological evidence of FTLD on biopsy or at post-mortem

  • C. Presence of a known pathogenic mutation.

V. Exclusionary criteria for bvFTD

Criteria A and B must be answered negatively for any bvFTD diagnosis. Criterion C can be positive for possible bvFTD but must be negative for probable bvFTD.

  • A. Pattern of deficits is better accounted for by other non-degenerative nervous system or medical disorders

  • B. Behavioural disturbance is better accounted for by a psychiatric diagnosis

  • C. Biomarkers strongly indicative of Alzheimer’s disease or other neurodegenerative process.

*As a general guideline 'early' refers to symptom presentation within the first 3 years.

Proposed research criteria for prodromal behavioural variant frontotemporal dementia[10]

Mild behavioural and/or cognitive impairment in bvFTD (MBCI-FTD) is a clinical syndrome defined by the presence of persistent and progressive decline in behaviour and/or cognition for more than 6 months based on observation or history provided by knowledgeable informant.

  1. Must be present to diagnose MBCI-FTD

    • A. Concern regarding behavioural and/or cognitive change from previous functioning, per informant, clinician, or patient

    • B. Preserved instrumental activities of daily living (unless due to physical impairment, e.g., motor neuron disease or parkinsonism)

    • C. >18 years old

  2. Possible MBCI-FTD

    At least three of the following core features (A-G) are sufficient, and must represent a change from previous behaviour, to diagnose possible MBCI-FTD

    • A. Apathy without moderate-severe dysphoria

    • B. Behavioural disinhibition

    • C. Irritability or agitation

    • D. Loss of empathy or sympathy

    • E. Repetitive behaviours (either E1 or E2)

      • E1. Simple: Aberrant motor behaviour, or restlessness (e.g., pacing, fidgeting, tapping)

      • E2. Complex: Perseverative, compulsive, or ritualistic behaviour (e.g., rigidity, rituals, hoarding)

    • F. Joviality or gregariousness

    • G. Appetite changes/hyperorality

    If only two of the core features (A-G) are present, then at least one of the following (H or I or J) must also be present to diagnose possible MBCI-FTD:

    • H. Neuropsychological deficits in context of intact or relatively preserved time/place orientation and visuospatial skills (one of H1 or H2 must be present)

      • H1. Clinical impairment or clinically significant decline on executive tasks (e.g., verbal generation, set-shifting, etc.)

      • H2. Clinical impairment or clinically significant decline on naming tests

    • I. Reduced insight for at least one aspect of behavioural or cognitive change

    • J. Impairments on standardised measures of social cognition (one of J1 or J2 must be present)

      • J1. Reduced understanding or awareness of social expectations

      • J2. Low socioemotional sensitivity

  3. Probable MBCI-FTD

    Both of the following (A and B) must be present to diagnose Probable MBCI-FTD:

    • A. Meets criteria for Possible MBCI-FTD

    • B. Genetic or biomarker evidence of FTLD (at least one of B1-B3 must be present)

      • B1. Presence of a known pathogenic mutation

      • B2. Imaging evidence of FTD

        • B2.1 Frontal and/or anterior temporal atrophy on MRI or CT

        • B2.2 Frontal and/or anterior temporal hypoperfusion or hypometabolism on PET or single-photon emission computed tomography (SPECT)

      • B3. Other plasma/cerebrospinal fluid (CSF) biomarkers indicative of FTLD pathology

  4. Exclusionary criteria for MBCI-FTD

    • A. History of sudden onset or other medical conditions severe enough to account for symptoms (e.g., cerebrovascular, infectious, toxic, inflammatory or metabolic disorders, traumatic brain injury or brain tumour)

    • B. Plasma or CSF or molecular imaging biomarkers more consistent with Alzheimer’s disease than FTLD

    • C. Meets diagnostic criteria for probable bvFTD

Consensus diagnostic criteria for the non-fluent/agrammatic variant primary progressive aphasia FTD[11]

Patients diagnosed with primary progressive aphasia (PPA) should be classified into one of three variants: non-fluent/agrammatic, semantic, and logopenic using the relevant consensus diagnostic criteria.

  • Clinical diagnosis of non-fluent/agrammatic variant PPA

    At least one of the following core features must be present:

    1. Agrammatism in language production

    2. Effortful, halting speech with inconsistent speech sound errors and distortions (apraxia of speech)

    At least 2 of the 3 following other features must be present:

    1. Impaired comprehension of syntactically complex sentences

    2. Spared single-word comprehension

    3. Spared object knowledge

  • Imaging-supported non-fluent/agrammatic variant diagnosis

    Both of the following criteria must be present:

    1. Clinical diagnosis of non-fluent/agrammatic variant PPA

    2. Imaging must show one or more of the following results:

      1. Predominant left posterior fronto-insular atrophy on MRI or

      2. Predominant left posterior fronto-insular hypoperfusion or hypometabolism on SPECT or PET

  • Non-fluent/agrammatic variant PPA with definite pathology

    Clinical diagnosis (criterion 1 below) and either criterion 2 or 3 must be present:

    1. Clinical diagnosis of non-fluent/agrammatic variant PPA

    2. Histopathological evidence of a specific neurodegenerative pathology (e.g., FTLD-tau, FTLD-TDP, Alzheimer’s disease, other)

    3. Presence of a known pathogenic mutation

Consensus diagnostic criteria for the semantic variant PPA FTD[11]

Patients diagnosed with primary progressive aphasia (PPA) should be classified into one of three variants: non-fluent/agrammatic, semantic, and logopenic using the relevant consensus diagnostic criteria.

  • Clinical diagnosis of semantic variant PPA

    Both of the following core features must be present:

    1. Impaired confrontation naming

    2. Impaired single-word comprehension

    At least 3 of the following other diagnostic features must be present:

    1. Impaired object knowledge, particularly for low-frequency or low-familiarity items

    2. Surface dyslexia or dysgraphia

    3. Spared repetition

    4. Spared speech production (grammar and motor speech)

  • Imaging-supported semantic variant PPA diagnosis

    Both of the following criteria must be present:

    1. Clinical diagnosis of semantic variant PPA

    2. Imaging must show one or more of the following results:

      1. Predominant anterior temporal lobe atrophy

      2. Predominant anterior temporal hypoperfusion or hypometabolism on SPECT or PET

  • Semantic variant PPA with definite pathology

    Clinical diagnosis (criterion 1 below) and either criterion 2 or 3 must be present:

    1. Clinical diagnosis of semantic variant PPA

    2. Histopathological evidence of a specific neurodegenerative pathology (e.g., FTLD-tau, FTLD-TDP, Alzheimer’s disease, other)

    3. Presence of a known pathogenic mutation

Consensus diagnostic criteria for logopenic variant PPA FTD[11]

Patients diagnosed with primary progressive aphasia (PPA) should be classified into one of three variants: non-fluent/agrammatic, semantic, and logopenic using the relevant consensus diagnostic criteria.

  • Clinical diagnosis of logopenic variant PPA

    Both of the following core features must be present:

    1. Impaired single-word retrieval in spontaneous speech and naming

    2. Impaired repetition of sentences and phrases

    At least 3 of the following other features must be present:

    1. Speech (phonologic) errors in spontaneous speech and naming

    2. Spared single-word comprehension and object knowledge

    3. Spared motor speech

    4. Absence of frank agrammatism

  • Imaging-supported logopenic variant diagnosis

    Both criteria must be present:

    1. Clinical diagnosis of logopenic variant PPA

    2. Imaging must show at least one of the following results:

      1. Predominant left posterior perisylvian or parietal atrophy on MRI

      2. Predominant left posterior perisylvian or parietal hypoperfusion or hypometabolism on SPECT or PET

  • Logopenic variant PPA with definite pathology

    Clinical diagnosis (criterion 1 below) and either criterion 2 or 3 must be present:

    1. Clinical diagnosis of logopenic variant PPA

    2. Histopathological evidence of a specific neurodegenerative pathology (e.g., Alzheimer’s disease, FTLD-tau, FTLD-TDP, other)

    3. Presence of a known pathogenic mutation

Diagnostic and statistical manual of mental disorders, 5th ed., text revision (DSM-5-TR) criteria for major or mild frontotemporal neurocognitive disorder[22][23]

A. The criteria are met for major or mild cognitive disorder.

  1. Major neurocognitive disorder: evidence of significant cognitive decline from a previous level of performance in one or more cognitive domains that interferes with independence in everyday activities. The cognitive deficits do not occur exclusively in the context of a delirium and are not better explained by another mental disorder.

    1. Specify severity:

      1. Mild: difficulties with instrumental activities of daily living (e.g., housework, managing money)

      2. Moderate: difficulties with basic activities of daily living (e.g., feeding, dressing)

      3. Severe: fully dependent.

    2. Specify:

      1. With agitation: If the cognitive disturbance is accompanied by clinically significant agitation

      2. With anxiety: If the cognitive disturbance is accompanied by clinically significant anxiety

      3. With mood symptoms: If the cognitive disturbance is accompanied by clinically significant mood symptoms (e.g., dysphoria, irritability, euphoria)

      4. With psychotic disturbance: If the cognitive disturbance is accompanied by delusions or hallucinations

      5. With other behavioural or psychological disturbance: If the cognitive disturbance is accompanied by other clinically significant behavioural or psychological disturbance (e.g., apathy, aggression, disinhibition, disruptive behaviours or vocalisations, sleep or appetite/eating disturbance)

      6. Without accompanying behavioural or psychological disturbance: If the cognitive disturbance is not accompanied by any clinically significant behavioural or psychological disturbance.

  2. Mild neurocognitive disorder: evidence of modest cognitive decline from a previous level of performance in one or more cognitive domains that does not interfere with independence in everyday activities. Greater effort, compensatory strategies, or accommodation may be required to preserve independence in complex instrumental activities of daily living (e.g., paying bills, managing drug treatments). The cognitive deficits do not occur exclusively in the context of a delirium and are not better explained by another mental disorder.

    1. Specify:

      1. Without behavioural disturbance: If the cognitive disturbance is not accompanied by any clinically significant behavioural disturbance

      2. With behavioural disturbance (specify disturbance): If the cognitive disturbance is accompanied by a clinically significant behavioural disturbance (e.g., apathy, agitation, anxiety, mood symptoms, psychotic disturbance, or other behavioural symptoms).

B. The disturbance has an insidious onset and gradual progression.

C. Either (1) or (2):

  1. Behavioural variant:

    1. Three or more of the following behavioural symptoms:

      1. Behavioural disinhibition

      2. Apathy or inertia

      3. Loss of sympathy or empathy

      4. Perseverative, stereotyped, or compulsive/ritualistic behaviour

      5. Hyperorality and dietary changes.

    2. Prominent decline in social cognition and/or executive abilities.

  2. Language variant:

    1. Prominent decline in language ability, in the form of speech production, word finding, object naming, grammar, or word comprehension.

D. Relative sparing of learning and memory and perceptual-motor function.

E. The disturbance is not better explained by cerebrovascular disease, another neurodegenerative disease, the effects of a substance, or another mental, neurological, or systemic disorder.

Probable frontotemporal neurocognitive disorder is diagnosed if either of the following is present; otherwise, possible frontotemporal neurocognitive disorder should be diagnosed:

  1. Evidence of a causative frontotemporal neurocognitive disorder genetic mutation, from either family history or genetic testing

  2. Evidence of disproportionate frontal and/or temporal lobe involvement from neuroimaging.

Possible frontotemporal neurocognitive disorder is diagnosed if there is no evidence of a genetic mutation, and neuroimaging has not been performed.

World Health Organization International Classification of Diseases 11 (ICD-11) mental, behavioural and neurodevelopmental disorders[140]

Essential (required) features for FTD:

  1. All diagnostic requirements for dementia are met

  2. Dementia is presumed to be attributable to underlying frontotemporal disease or atrophy, as demonstrated by neuropsychological test data, neuroimaging data, genetic testing, medical tests, family history, and/or clinical history.

Additional clinical features:

  1. Frontotemporal dementia variants include primary progressive aphasia (logopenic, semantic, and agrammatic subtypes), behavioural frontotemporal dementia, and motoric frontotemporal dementia (corticobasal degeneration, progressive supranuclear palsy, and amyotrophic lateral sclerosis).

  2. Frontotemporal dementia is progressive, with variants identified based on initial symptoms:

    1. Frontotemporal dementia, behavioural variant, is characterised by personality changes, often including apathy and progressively inappropriate social behaviour. Neurocognitive functioning may be preserved in the early stages, though the progression may later involve deficits in executive functioning (e.g., planning, problem solving), with comparatively intact memory skills.

    2. Frontotemporal dementia, primary progressive aphasia, is characterised by progressive impairment in language skills, initially in the absence of impairment in other cognitive skills. Subtypes of primary progressive aphasia are often determined based on neuropsychological/cognitive testing, clinical presentation and sometimes neuroimaging, and are characterised by primary deficits in word finding (logopenic subtype), word meaning (semantic subtype), or word production (agrammatic subtype).

    3. Frontotemporal dementia, motoric variant, involves progressive impairment in motor functioning, sometimes in the context of progressive neurocognitive impairment (typically characterised by impairment in attention, executive functioning, and visuospatial skills, with comparatively intact memory skills). Frontotemporal dementia, motoric variant, can include progressive supranuclear palsy (e.g., poor balance, frequent falls, visual impairment from gaze palsy), corticobasal degeneration (e.g., limb apraxia, tripping, rigidity, dystonia), and amyotrophic lateral sclerosis (e.g., muscle weakness, muscle atrophy, fasciculations, spasticity).

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