Demensia Frontotemporal

01Pathophysiology

Frontotemporal dementia results from progressive degeneration of neurons in the frontal and anterior temporal lobes of the brain. This anatomic pattern directly explains the clinical features: the frontal lobes govern executive function, judgment, social behavior, and impulse control, while the anterior temporal lobes are critical for language, semantic knowledge, and emotional processing.

At the molecular level, the disease is classified under the umbrella term frontotemporal lobar degeneration (FTLD). FTD can be classified neuropathologically based on the predominant protein abnormalities, with four molecular subgroups currently established: FTLD-Tau, characterized by tau depositions; FTLD-TDP, characterized by TDP-43 aggregates; FTLD-FET, involving proteins of the FET protein family; and rare cases classified as FTLD-UPS. In practice, the two dominant proteinopathies are tau and TDP-43.

The genetic basis is important for exam purposes. Approximately one fifth of all FTD cases have a monogenic cause, and of these, about 80% are explained by variants in C9orf72, MAPT, or GRN. The MAPT gene encodes tau protein, and its mutations lead to FTLD-Tau pathology. Mutations in GRN (progranulin) and hexanucleotide repeat expansions in C9orf72 are both associated with TDP-43 pathology. The C9orf72 hexanucleotide repeat expansion represents the most common genetic cause of both FTD and ALS, with the mean age of onset between 45 and 64 years and a median survival time of 7 to 13 years after symptom onset.

The connection between pathology and symptoms is straightforward: frontal lobe degeneration produces the behavioral syndrome (disinhibition, apathy, compulsive behaviors), while temporal lobe degeneration produces the language syndromes (semantic loss or nonfluent speech). The PNPK Demensia 2026 confirms that behavioral and language disturbances are the core features of FTD, and that patients have relatively preserved memory, which is the cardinal distinction from Alzheimer disease.

Because the cholinergic system is not primarily affected in FTD (unlike in Alzheimer disease), cholinesterase inhibitors are not helpful and may worsen symptoms. The serotonergic system, however, shows significant deficits in the frontal and temporal cortex, providing the rationale for SSRI use.

02Classification and Clinical Manifestation

According to the PNPK Demensia 2026, bvFTD is the most common variant. The early symptoms that appear within the first three years of bvFTD include disinhibition, apathy, loss of sympathy or empathy, perseverative/stereotypical/compulsive behavior, and hyperorality.

The 2011 consensus criteria for bvFTD focus on six core clinical features: five behavioral (disinhibition, apathy, loss of sympathy/empathy, compulsive behaviors, and hyperorality) and one cognitive (dysexecutive profile with preservation of episodic memory and visuospatial ability).

03Diagnostic Workup

The workup begins with a thorough clinical history, ideally corroborated by a caregiver or family member. This is critical because patients with bvFTD typically lack insight into their behavioral changes and may appear normal during a brief clinical encounter. Neuropsychological testing is the most informative initial step because it can reveal the signature pattern of impaired executive function (poor abstraction, set-shifting, response inhibition) alongside preserved memory performance, which distinguishes FTD from Alzheimer disease.

The PNPK Demensia 2026 recommends that structural neuroimaging with CT or MRI be performed on patients with cognitive complaints, and that MRI is preferred over CT when facilities are available. For FTD, MRI demonstrates focal cortical atrophy in the frontal and/or temporal regions. The guideline notes that semi-quantitative scoring such as the GCA (Global Cortical Atrophy) scale can be useful, and that studies have demonstrated Alzheimer patients show thinner cortex in the bilateral parietal and precuneus regions compared to FTD patients. Importantly, the guideline notes that serial volumetric MRI can help predict disease progression in Alzheimer, vascular, and FTD types of dementia.

The PNPK Demensia 2026 states that FDG-PET imaging is effective and accurate for differential diagnosis in patients with cognitive impairment who have already undergone clinical evaluation and structural imaging, but where the underlying pathological process remains unclear. If FDG-PET is unavailable, SPECT rCBF (regional cerebral blood flow) can serve as an alternative.

CSF biomarkers are not routinely recommended by the PNPK Demensia 2026, but can be considered when diagnostic uncertainty exists, particularly in patients with early-onset dementia (<65 years) or when the clinical presentation is atypical. The guideline confirms that CSF biomarkers (amyloid-beta, tau, p-tau) are highly sensitive and have good accuracy for distinguishing Alzheimer disease from normal aging, but show lower sensitivity in differentiating between subtypes of dementia such as FTD, DLB, and vascular dementia. Their primary role in FTD is therefore to rule out underlying Alzheimer pathology.

04Management and Treatment

The first and most critical step is non-pharmacological intervention. The PNPK Demensia 2026 emphasizes that the management of behavioral symptoms in all dementias, including FTD, should begin with psychosocial approaches: environmental modification, structured daily routines, caregiver education, and individualized behavioral plans. Pharmacotherapy is added only when these measures fail.

When medications are needed, the PNPK Demensia 2026 recommends SSRIs as the pharmacological treatment for FTD, started at low doses with gradual titration and caregiver monitoring. The guideline notes that escitalopram or citalopram can produce changes on MMSE scores, though no significant benefit was found for SSRI treatment of mood disturbance or agitation in FTD overall. Sertraline is commonly used given its balanced efficacy profile.

Expert consensus from the ERN-RND recommends SSRIs for perseverative somatic complaints, rigidity of thought, hyperphagia, loss of empathy, and impulsivity, while trazodone is recommended for motor unrest, mirtazapine for nightly unrest, and bupropion and methylphenidate for apathy.

A systematic review found that trazodone had the greatest effect on reducing behavioral symptoms of bvFTD based on the NPI, and that citalopram, rivastigmine, paroxetine, and trazodone all reduced multiple symptoms including disinhibition, hyperorality, and depression.

The contraindication of AChEIs in FTD is a very testable point. The PNPK Demensia 2026 explicitly states this: a study of FTD patients treated with donepezil (10 mg for 6 months) showed worsening of compulsive behavior and overall deterioration of FTD inventory scores. Withdrawal of donepezil was followed by behavioral improvement. Similarly, two RCTs of memantine in FTD showed no significant benefit and some evidence of worse cognitive performance.

05Differential Diagnosis and Distractors

06Traps and High-Yield Pearls

The single most common trap with FTD questions is confusing it with Alzheimer disease. A vignette describing a patient younger than 65 years old who presents with personality change, socially inappropriate conduct, or apathy, with relatively preserved memory, is FTD until proven otherwise. Students frequently default to "Alzheimer" for any dementia question, but the exam tests whether you can recognize the preserved-memory, behavioral-onset pattern that points to FTD.

The second major trap is prescribing cholinesterase inhibitors. This is wrong for FTD. The PNPK Demensia 2026 explicitly warns against AChEIs and memantine in FTD. If the vignette establishes FTD and then asks about treatment, the answer is SSRI or trazodone, never donepezil or memantine. A distractor answer offering "donepezil for cognitive decline" is designed to catch students who treat all dementias the same way.

A third trap involves the language variants. Students may see a vignette describing progressive word-finding difficulty or loss of object knowledge and think of a stroke or brain tumor. The key is the word "progressive" over months to years. Acute language loss is stroke; progressive language loss without motor deficits is PPA (primary progressive aphasia, a form of FTD).

The fourth testable concept is C9orf72-related FTD. If the vignette includes FTD with concurrent motor neuron disease features (fasciculations, muscle atrophy, upper motor neuron signs), think C9orf72. This expansion is unique in that it links FTD and ALS on a single genetic spectrum.

Finally, the core competency being tested is pattern recognition: young patient + behavioral change + preserved memory + frontal atrophy = FTD. The exam rewards your ability to recognize this gestalt, order the correct imaging (MRI showing frontotemporal atrophy), avoid the wrong treatment (AChEIs), and select the right treatment (SSRIs, trazodone, non-pharmacological support).