Frontotemporal lobar degeneration (FTLD) is a group of progressive memory disorders with atrophy in the frontotemporal lobes of the brain.
Frontotemporal dementia
Primary progressive aphasia
Progressive nonfluent aphasia
Semantic dementia
Logopenic progressive aphasia
FTLD plus syndromes
Progressive supranuclear palsy (PSP)
Corticobasal degeneration
About 30% of all progressive memory disorders belong to the FTLD group.
In about 50% of patients, excluding those with FTLD plus syndromes, there is a positive family history.
The most common genetic aetiology associated with frontotemporal lobar degeneration is a non-coding repeat expansion of the C9orf72 (chromosome 9 open-reading frame 72) gene.
Study of the C9orf72 mutation may be beneficial for the diagnosis of these diseases.
FTLD patients of non-Finnish origin commonly have mutations in GRN and MAPT genes, as well.
Genetic testing is done in specialized care.
As frontotemporal lobar degeneration may have several underlying neuropathological subtypes, there are no specific biomarkers available for the disease.
CSF biomarker (tau, p-tau and amyloid β) tests used for the diagnosis of Alzheimer's disease do not reliably distinguish between frontotemporal lobar degeneration and Alzheimer's disease.
Normal findings in conventional cognitive screening tests (CERAD and MMSE) do not exclude diseases of the FTLD group.
The disease should primarily be diagnosed and treatment started by a neurologist, geriatrician or other physician with expertise in memory disorders.
Frontotemporal dementia
Accounts for about half of all cases of FTLD.
Disease onset usually occurs between the ages of 45 and 65.
Hereditary disease, in particular, may begin as early as at the age of 30.
FTLD with onset after the age of 70 is not rare, either.
The average duration of the disease is 8 years but there is substantial variation (2-20 years).
Typical clinical features:
Changes in behaviour and personality (disinhibition, impulsiveness, tactlessness, impaired judgement)
Problems with executive functions (planning, ability to concentrate, attention)
Early impairment of social skills
Apathy and introversion
Decline in reasoning ability and problem solving
Impaired speech production
Diminished insight into the disease
Hyperorality, i.e. changes in eating/drinking habits (binge eating, particularly craving for sweet foods, increased consumption of alcohol or tobacco)
Subjective memory symptoms
Extrapyramidal symptoms and findings (rigidity, hypomimia, hypo- and bradykinesia)
Psychosis-like symptoms
Atrophy in the frontal and/or temporal lobes can be detected by magnetic resonance imaging (MRI) of the brain, and functional imaging techniques (PET, SPECT) can detect corresponding hypoperfusion and hypometabolism.
In early and moderately severe disease, imaging may give normal findings.
Alzheimer's drugs are contraindicated, as they often aggravate the clinical picture.
Symptomatic treatment
Usual treatment of psychotic and affective symptoms
Antipsychotics, in particular, should be used at the lowest possible doses, as the patients are sensitive to extrapyramidal adverse effects.
Benzodiazepines should mostly be avoided since the disease pathology involves damage to the gamma-aminobutyric acid system.
Regular assessment of driving ability and legal competence
Ensuring a well-balanced diet and treatment of any deficiencies
The disease is often complicated by other problems associated with general care.
Progressive nonfluent aphasia
Typical clinical features:
Insidious onset and gradual progression
Laboured, fragmental speech
Dyslalia and paraphasia (apraxia of speech)
Impaired comprehension of grammatically complicated sentences
Comprehension of single words preserved
Face and object recognition preserved
MRI of the brain shows atrophy usually in the left frontal lobe and the anterior areas of the temporal lobe.
Semantic dementia
Typical clinical features:
Insidious onset and gradual progression
Language output in conversation is fluent but the speech does not convey meaning.
Evident difficulty naming things
Difficulty understanding words
Impaired recognition of faces and objects
Difficulty reading and writing
Repetition of words and sentences is effortless but understanding of the content is gradually lost.
Speech is well articulated and grammatically normal.
Behavioural changes
Lack of insight into symptoms
MRI of the brain shows atrophy in the area of the middle and inferior temporal gyri.
Logopenic progressive aphasia
Typical clinical features:
Finding words in speech and naming is impaired.
Repetition of sentences or phrases is impaired.
Dyslalia in spontaneous speech and naming
Understanding of individual words and recognition of faces and objects are preserved.
Motorically, speech is effortless.
No significant grammatical mistakes
Memory symptoms during the first few years
Progressive supranuclear palsy
First symptoms usually at the age of about 50-60 years
Average duration of disease approx. 5-8 years
Typical clinical features:
A tendency to fall backward
Vertical disturbance of eye movements (difficulty aiming the eyes downward, in particular)
Staring gaze, hypomimia
Symmetric rigidity of the neck and trunk, in particular
Other extrapyramidal findings and symptoms (rigidity, hypo- and bradykinesia)
Later often problems with swallowing, slurred speech