Differences

Last edited on January 23, 2024

This shows you the differences between two versions of the page.

--- geri:dementia:frontotemporal [on December 8, 2018]
+++ geri:dementia:frontotemporal [on May 16, 2019]
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+====== Frontotemporal Dementia (FTD) ======
+===== Primer =====
+**Frontotemporal dementia (FTD)**, also known as lobar degeneration (FTLD), or less commonly, Pick's disease, is the most common causes of dementia in adults younger than 60 years. It is characterized by uninhibited behavior, hyperorality, lack of empathy, impaired executive function, and lack of sympathy. Loss of insight is one of the core features of the frontal/behavioural variant frontotemporal dementia (FTD).
+== Prevalence ==
+Approximately 2-10 per 100,000 people. Approximately 20%-25% of cases of frontotemporal NCD occur in individuals older than 65 years. Frontotemporal NCD accounts for approximately 5% of all cases of dementia. The behavioral variants and semantic language variant are higher in males, and and nonfluent language variant are higher among females.
+== Disease Course ==
+The disease is gradually progressive, with a median survival of 5-10 years after symptom onset and 4 years after diagnosis.
+==== Subtypes ====
+<WRAP group>
+<WRAP half column>
+Frontotemporal dementia can be classified into four clinical variants:[([[https://www.ncbi.nlm.nih.gov/pubmed/26595641|Bang, J., Spina, S., & Miller, B. L. (2015). Frontotemporal dementia. The Lancet, 386(10004), 1672-1682.]])]
+  - **Behavioral (or frontal) Variant** (BV-FTD) - there is relative preservation of recall, and behaviour is usually the first change
+  - **Semantic Variant [[geri:dementia:ppa|Primary Progressive Aphasia]]** (SV-PPA)
+  - **Logopenic Variant**
+  - **Non-fluent (agrammatic) Variant [[geri:dementia:ppa|Primary Progressive Aphasia]]** (NFV-PPA) - patients are often stumbling for words, and grammar is very poor
+</WRAP>
+<WRAP half column>
+<callout type="success">{{fa>arrow-circle-right?color=green}} See main article: **[[geri:dementia:ppa|]]**</callout>
+</WRAP>
+</WRAP>
+==== ALS ====
+ALS (Amyotrophic Lateral Sclerosis) and FTD have a considerable clinical and pathological overlap. A pathogenic hexanucleotide repeat expansion within the //C9ORF72// gene is thought to be a major cause of both disorders.[([[https://www.nature.com/articles/s41598-017-02364-1|Murphy, N. A., Arthur, K. C., Tienari, P. J., Houlden, H., Chiò, A., & Traynor, B. J. (2017). Age-related penetrance of the C9orf72 repeat expansion. Scientific reports, 7(1), 2116.]])] Indeed, a proportion of patients with FTD also develop ALS.[([[https://www.ncbi.nlm.nih.gov/pubmed/28387671|Neumann, M., Sampathu, D. M., Kwong, L. K., Truax, A. C., Micsenyi, M. C., Chou, T. T., ... & McCluskey, L. F. (2006). Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science, 314(5796), 130-133.]])]
+===== Symptoms =====
+Individuals with behavioral-variant frontotemporal dementia may present with apathy or disinhibition. Patients typically lose interest in socialization, self care, and personal responsibilities, or display socially inappropriate behaviours, such as sexual disinhibition. Insight is usually impaired as well. Cognitive impairment is much less prominent during the early stages, and few deficits are found on cognitive testing.
+===== Diagnostic Criteria =====
+<WRAP group>
+<WRAP half column>
+== Criterion A ==
+The criteria are met for [[cl:2-major-neurocog-disorder|major]] or [[cl:3-mild-neurocog-disorder|mild neurocognitive disorder]].
+== Criterion B ==
+The disturbance has insidious onset and gradual progression.
+== Criterion C ==
+Either (1) or (2);
+  - Behavioural variant
+    * a. ''3'' or more of the following behavioural symptoms:
+      * Behavioural disinhibition
+      * Apathy or inertia
+      * Loss of sympathy or empathy
+      * Perseverative, stereotyped or compulsive/ritualistic behaviour
+      * Hyperorality and dietary changes
+    * b. Prominent decline in social cognition and/or executive abilities
+  - Language variant
+    * a. Prominent decline in language ability, in the form of speech production, word finding, object naming, grammar, or word comprehension.
+</WRAP>
+<WRAP half column>
+== Criterion D ==
+Relative sparing of learning and memory and perceptual-motor function.
+== Criterion 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 vs. Possible ====
+**Probable frontotemporal neurocognitive disorder** is diagnosed if either of the following is present; otherwise, possible frontotemporal neurocognitive disorder should be diagnosed:
+  - Evidence of a causative frontotemporal neurocognitive disorder genetic mutation, from either family history or genetic testing.
+  - 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.
+</WRAP>
+</WRAP>
+===== Pathophysiology =====
+Genetic mutations associated with FTD include the encoding of microtubule-associated protein tau (MAPT) and granulin (GRN), C90RF72,[([[https://bmcneurol.biomedcentral.com/articles/10.1186/s12883-014-0228-6|Gramaglia, C., Cantello, R., Terazzi, E., Carecchio, M., D’Alfonso, S., Chieppa, N., ... & Zeppegno, P. (2014). Early onset frontotemporal dementia with psychiatric presentation due to the C9ORF72 hexanucleotide repeat expansion: a case report. BMC neurology, 14(1), 228.]])] transactive response DNA-binding protein of 43 kDa (TDP-43, or TARDBP), valosin-containing protein (VCP), chromatin modifying protein 2B (CHMP2B), and fused in sarcoma protein (PUS). The majority of FTD cases remain sporadic.
+===== Investigations =====
+==== Computed Tomography ====
+A CT head or MRI head can show patterns of atrophy of the frontal lobes that can aid in the clinical diagnosis. Neuroimaging is also helpful to exclude other differential diagnoses such as mass lesions and hydrocephalus.
+<panel title="Neuroimaging Findings" no-body="true">
+^ Variant             ^ Neuroimaging Findings                                                                                                                      ^
+^ Behavioral variant  | Both frontal lobes (in particular the medial frontal lobes) and anterior temporal lobes have atrophy                                       |
+^ Semantic variant    | Middle, inferior, and anterior temporal lobes are atrophic bilaterally but asymmetrically, with the left side usually being more affected  |
+^ Logopenic variant   | Associated with predominantly left posterior perisylvian or parietal atrophy                                                               |
+^ Nonfluent variant   | Associated with predominantly left posterior frontal-insular atrophy                                                                       |
+</panel>
+==== Cognitive Testing ====
+The [[cognitive-testing:fab|]] is commonly used as a screening test. The [[cognitive-testing:moca|Montreal Cognitive Assessment (MoCA)]] can also be used to screen for early mild cognitive changes. Since the [[cognitive-testing:mmse|Mini-Mental Status Exam (MMSE)]] does not include an assessment for impaired executive function, it may not detect changes indicative of FTD.
+===== Differential Diagnosis =====
+  * [[geri:dementia:alzheimers|]] - about 10%-30% of patients presenting symptoms suggestive of FTD are found at autopsy to have Alzheimer's disease pathology.
+  * [[geri:dementia:progressive-supranuclear-palsy-psp|progressive supranuclear palsy]] (PSP), [[geri:dementia:corticobasal-degeneration-cbd|corticobasal degeneration]] (CBD) - FTD overlaps with on brain pathology
+  * [[geri:dementia:creutzfeldt-jakob-disease-cjd|]] - usually has a much more progressive onset, compared to FTD, which is slowly progressive
+===== Treatment =====
+There are no approved treatments for FTD. All current treatments are thus off-label and used to manage symptoms of the disease.[([[https://www.ncbi.nlm.nih.gov/pubmed/25238733|Tsai, R. M., & Boxer, A. L. (2014). Treatment of frontotemporal dementia. Current treatment options in neurology, 16(11), 319.]])] In fact, the evidence suggests cholinesterase inhibitors may exacerbate behavioural symptoms. Antidepressants as a class have been shown to lead to some behavioural improvement.[([[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4824317/|Bott, N. T., Radke, A., Stephens, M. L., & Kramer, J. H. (2014). Frontotemporal dementia: diagnosis, deficits and management. Neurodegenerative disease management, 4(6), 439-454.]])]
+== Behavioural Symptoms ==
+For behavioural symptoms, SSRIs may be effective, including: [[meds:antidepressants:ssri:citalopram|citalopram]], [[meds:antidepressants:ssri:fluoxetine|fluoxetine]], and [[meds:antidepressants:ssri:sertraline|sertraline]]. Trazodone similarly has evidence for the treatment of behavioural symptoms related to FTD[([[https://www.ncbi.nlm.nih.gov/pubmed/15178953|Lebert, F.,.nlm.nih.gov/pubmed/ Stekke, W., Hasenbroekx, C., & Pasquier, F. (2004). Frontotemporal dementia: a randomised, controlled trial with trazodone. Dementia and Geriatric Cognitive Disorders, 17(4), 355-359.]])] Antipsychotics and anti-epileptics have also been shown to be effective in the management of behavioural symptoms, but are limited in use due to their side effect profile. Like with managing all forms of [[geri:dementia:1-bpsd|behavioural symptoms of dementia]] it is very important to rule out potential triggers for behavioural disturbances such as infections, electrolyte changes, medical issues, and environmental stressors prior to initiating psychotropic medications.
+===== Resources =====
+== Clinical Cases ==
+  * [[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5549462/|Kelley, R. E., & El-Khoury, R. (2016). Frontotemporal dementia. Neurologic clinics, 34(1), 171-181.]]