Differences

Last edited on April 30, 2020

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

--- geri:dementia:frontotemporal [on June 2, 2019]
+++ geri:dementia:frontotemporal [on January 23, 2024] (current)
psychdb [Primer]
@@ Line 1: / Line 1: @@
 ====== Frontotemporal Dementia (FTD) ======
+{{INLINETOC}}
 ===== 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).
+**Frontotemporal dementia (FTD)**, also known as **frontotemporal lobar degeneration (FTLD)**, or less commonly, Pick's disease, is one of the most common causes of dementia in adults younger than 60 years. FTD is actually an umbrella clinical term that encompasses a group of neurodegenerative diseases (behavioural-variant frontotemporal dementia, non-fluent variant [[geri:dementia:primary-progressive-aphasia-ppa|primary progressive aphasia]], and semantic-variant [[geri:dementia:primary-progressive-aphasia-ppa|primary progressive aphasia]]). Individuals with behavioural variant may have disinhibited 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). Those with primary progressive aphasia will have progressive deficits in speech, grammar, word output, semantic knowledge, or naming.
-== Prevalence ==
+== Epidemiology ==
-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.
+  * FTD is the second or third most common dementia in most meta-analytic studies, after [[geri:dementia:alzheimers|Alzheimer's]] and [[geri:dementia:lewy-body|dementia with Lewy bodies]].
+    * Affects approximately 2-10 per 100,000 people.
+    * Frontotemporal dementias accounts for approximately 5% of all cases of dementia.
+  * The peak age of onset is between ages 45-70, and has a "presenile" onset compared to other dementias.
+    * Approximately 10% of cases have onset before age 45 years.
+    * Approximately 60% of cases have onset between 45-64 years, and about 30% of cases occur in individuals older than 65 years.[([[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5970949/|Bang, J., Spina, S., & Miller, B. L. (2015). Frontotemporal dementia. The Lancet, 386(10004), 1672-1682.]])]
+  * Overall, more males are affected than females.
+    * The behavioural variants and semantic language variant are higher in males, while and non-fluent language variant are higher among females.
-== Disease Course ==
+== Prognosis ==
-The disease is gradually progressive, with a median survival of 5-10 years after symptom onset and 4 years after diagnosis.
+  * The disease is gradually progressive, with a median survival of 5-10 years after symptom onset and 4 years after diagnosis.[([[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5970949/|Bang, J., Spina, S., & Miller, B. L. (2015). Frontotemporal dementia. The Lancet, 386(10004), 1672-1682.]])]
-==== 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:primary-progressive-aphasia-ppa|Primary Progressive Aphasia]]** (SV-PPA)
-  - **Logopenic Variant**
-  - **Non-fluent (agrammatic) Variant [[geri:dementia:primary-progressive-aphasia-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:primary-progressive-aphasia-ppa]]**</callout>
-</WRAP>
+== Comorbidity ==
-</WRAP>
+  * A high rate of [[psychosis:schizophrenia-scz|late-onset psychosis]] is a characteristic feature of inherited frontotemporal dementia associated with //C9ORF72// mutations, the most common genetic form of the disorder.
+    * //C9ORF72// mutations are also associated with [[psychosis:schizophrenia-scz|schizophrenia]] and [[bipolar:bipolar-i|bipolar disorder]].[([[https://pubmed.ncbi.nlm.nih.gov/28238272/|Ducharme, S., Bajestan, S., Dickerson, B. C., & Voon, V. (2017). Psychiatric presentations of C9orf72 mutation: what are the diagnostic implications for clinicians?. The Journal of neuropsychiatry and clinical neurosciences, 29(3), 195-205.]])]
+  * There is a substantial overlap of symptoms between Alzheimer’s disease and frontotemporal dementia.
-==== ALS ====
+== Risk Factors ==
-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.]])]
+  * Genetics is an important risk factor for frontotemporal dementia.
-===== Symptoms =====
+    * A family history of dementia is reported in up to 40% of cases of frontotemporal lobar degeneration, although a clear autosomal dominant history accounts for only 10% of cases
-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.
+===== DSM-5 Diagnostic Criteria =====
-===== Diagnostic Criteria =====
 <WRAP group>
 <WRAP half column>
@@ Line 38: / Line 36: @@
 == Criterion C ==
 Either (1) or (2);
-  - Behavioural variant
+  - **Behavioural variant**
     * a. ''3'' or more of the following behavioural symptoms:
       * Behavioural disinhibition
@@ Line 46: / Line 44: @@
       * Hyperorality and dietary changes
     * b. Prominent decline in social cognition and/or executive abilities
-  - Language variant
+  - **Language variant**
     * a. Prominent decline in language ability, in the form of speech production, word finding, object naming, grammar, or word comprehension.
 </WRAP>
@@ Line 64: / Line 62: @@
 </WRAP>
 </WRAP>
+==== Symptoms ====
+<WRAP group>
+<WRAP half column>
+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.
+</WRAP>
+<WRAP half column>
+<callout icon="fa fa-lightbulb-o" type="success" title="Mnemonic">
+The mnemonic ''**BEACH**'' can be used to remember the core symptoms of behavioural variant of FTD
+\\ \\
+  * ''**B**'' - Behavioural disinhibition
+  * ''**E**'' - Empathy decrease
+  * ''**A**'' - Apathy
+  * ''**C**'' - Compulsions
+  * ''**H**'' - Hyperorality
+</callout>
+</WRAP>
+</WRAP>
+===== FTDC Criteria =====
+The International Behavioural Variant FTD Criteria Consortium (FTDC) developed revised guidelines for the diagnosis of bvFTD in 2011 that are more comprehensive than the DSM-5.[([[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3170532/|Rascovsky, K., Hodges, J. R., Knopman, D., Mendez, M. F., Kramer, J. H., Neuhaus, J., ... & Hillis, A. E. (2011). Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain, 134(9), 2456-2477.]])]
+<WRAP group>
+<WRAP half column>
+== 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 ==
+''3'' 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 [''1'' of the following symptoms (A1–A3) must be present]:
+    * A1. Socially inappropriate behaviour
+    * A2. Loss of manners or decorum
+    * A3. Impulsive, rash or careless actions
+  * **B**. Early apathy or inertia [''1'' of the following symptoms (B1–B2) must be present]:
+    * B1. Apathy
+    * B2. Inertia
+  * **C**. Early loss of sympathy or empathy [''1'' of the following symptoms (C1–C2) must be present]:
+    * C1. Diminished response to other people’s needs and feelings
+    * C2. Diminished social interest, interrelatedness or personal warmth
+  * **D**. Early perseverative, stereotyped or compulsive/ritualistic behaviour [''1'' of the following symptoms (D1–D3) must be present]:
+    * D1. Simple repetitive movements
+    * D2. Complex, compulsive or ritualistic behaviours
+    * D3. Stereotypy of speech
+  * **E**. Hyperorality and dietary changes [''1'' of the following symptoms (E1–E3) must be present]:
+    * E1. Altered food preferences
+    * E2. Binge eating, increased consumption of alcohol or cigarettes
+    * E3. 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 (F1–F3) must be present]:
+    * F1. Deficits in executive tasks
+    * F2. Relative sparing of episodic memory
+    * F3. Relative sparing of visuospatial skills
+</WRAP>
+<WRAP half column>
+== 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 caregiver report or as evidenced by Clinical Dementia Rating Scale or Functional Activities Questionnaire scores)
+  * **C**. Imaging results consistent with bvFTD [''1'' of the following (C1–C2) must be present]:
+    * C1. Frontal and/or anterior temporal atrophy on MRI or CT
+    * C2. Frontal and/or anterior temporal hypoperfusion or hypometabolism on PET or SPECT
+== IV. Behavioural variant FTD with definite 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
+<callout>
+* = As a general guideline ‘early’ refers to symptom presentation within the first 3 years
+</callout>
+</WRAP>
+</WRAP>
+===== Subtypes =====
+<alert icon="fa fa-arrow-circle-right fa-lg fa-fw" type="success">See main article: **[[geri:dementia:primary-progressive-aphasia-ppa]]**</alert>
+Frontotemporal dementia can be classified into different clinical variants or subtypes:[([[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** (bvFTD) - there is relative preservation of recall, and behaviour is usually the first change
+  - **Semantic variant [[geri:dementia:primary-progressive-aphasia-ppa|primary progressive aphasia]]** (svPPA, or PPA-S), patients have difficulty naming objects, difficulty with single-word comprehension, but speech production is spared along with repetition
+  - **Non-fluent (agrammatic) variant [[geri:dementia:primary-progressive-aphasia-ppa|primary progressive aphasia]] (nfvPPA or PPA-G)**, patients are often stumbling for words and grammar is very poor
+  - **Logopenic variant [[geri:dementia:primary-progressive-aphasia-ppa|primary progressive aphasia]] (lvPPA or PPA-L)**, usually rare in FTD, and more commonly seen in Alzheimer's. Patients have impaired naming and repetition, but grammar and single-word comprehension is preserved
+  - Additionally, there is FTD overlaps with other tauopathies, including [[geri:dementia:progressive-supranuclear-palsy-psp|progressive supranuclear palsy]] (PSP), [[geri:dementia:corticobasal-degeneration-cbd|corticobasal degeneration]] (CBD).
+==== 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.]])]
 ===== 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.
+  * The majority of FTD cases remain sporadic.
+  * Genetic mutations associated with FTD include the encoding of microtubule-associated protein tau (MAPT), TANK-binding kinase 1 (TBK-1),[([[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4691687/|Gijselinck, I., Van Mossevelde, S., van der Zee, J., Sieben, A., Philtjens, S., Heeman, B., ... & Van Broeckhoven, C. (2015). Loss of TBK1 is a frequent cause of frontotemporal dementia in a Belgian cohort. Neurology, 85(24), 2116-2125.]])], granulin (GRN), C9orf72,[([[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 ([[geri:dementia:late-tdp-43|TDP-43]], or TARDBP), valosin-containing protein (VCP), chromatin modifying protein 2B (CHMP2B), and fused in sarcoma protein (PUS).
+  * The orbitofrontal cortex (OFC) is the first area of the brain that shows atrophy and volume loss when FTD develops.[([[https://pubmed.ncbi.nlm.nih.gov/16914925/|Perry, R. J., Graham, A., Williams, G., Rosen, H., Erzinçlioglu, S., Weiner, M., ... & Hodges, J. (2006). Patterns of frontal lobe atrophy in frontotemporal dementia: a volumetric MRI study. Dementia and geriatric cognitive disorders, 22(4), 278-287.]])] The OFC is the anatomical region associated with normal social and emotional behaviour, stimulus-reward reversal learning, response inhibition, and appropriate behaviours in social contexts.[([[https://pubmed.ncbi.nlm.nih.gov/17846163/|Viskontas, I. V., Possin, K. L., & Miller, B. L. (2007). Symptoms of frontotemporal dementia provide insights into orbitofrontal cortex function and social behavior. Annals of the New York Academy of Sciences, 1121(1), 528-545.]])]
+===== Differential Diagnosis =====
+  * **Primary psychiatric disorders**
+    * **[[mood:1-depression:geriatric|Late-life depression]]**
+    * **[[psychosis:schizophrenia-scz|Late-onset psychosis or schizophrenia]]**
+    * **[[bipolar:bipolar-i|Late-onset bipolar disorder]]**
+  * **Neurodegenerative disorders**
+    * **Phenocopy syndrome of behavioural variant frontotemporal dementia**[([[https://pubmed.ncbi.nlm.nih.gov/30935398/|Valente, E. S., Caramelli, P., Gambogi, L. B., Mariano, L. I., Guimarães, H. C., Teixeira, A. L., & de Souza, L. C. (2019). Phenocopy syndrome of behavioral variant frontotemporal dementia: a systematic review. Alzheimer's research & therapy, 11(1), 1-15.]])]
+      * The absence of atrophy in bvFTD is very unusual (as you usually should see atrophy), so one might consider bvFTD phenotype syndrome if there are neuropsychiatric symptoms mimicking bvFTD, but lacking the classic frontotemporal atrophy/hypometabolism on neuroimaging and also not evolving to dementia during follow-up.
+    * **[[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 with both PSP and CBD.
+    * **[[geri:dementia:creutzfeldt-jakob-disease-cjd|]]**
+      * Usually has a much more progressive onset, compared to FTD, which is slowly progressive.
 ===== Investigations =====
-==== Computed Tomography ====
+==== Bloodwork ====
+  * Blood work includes comprehensive metabolic panels, liver and kidney function tests, complete blood count, vitamin B12 concentration, and thyroid hormone levels.
+  * Cerebrospinal fluid assessment should be done in atypical cases.
+  * Toxic (heavy metals, illicit drugs), inflammatory (autoimmune, paraneoplastic), or infectious (syphilis, HIV) causes should be considered in certain cases.[([[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5970949/|Bang, J., Spina, S., & Miller, B. L. (2015). Frontotemporal dementia. The Lancet, 386(10004), 1672-1682.]])]
+==== Neuroimaging ====
 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                                                                                                                      ^
+^ Variant             ^ Neuroimaging Findings                                                                                                                          ^
-^ Behavioral variant  | Both frontal lobes (in particular the medial frontal lobes) and anterior temporal lobes have atrophy                                       |
+^ 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  |
+^ 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                                                               |
+^ Logopenic variant   | Associated with predominantly **left** posterior perisylvian or parietal atrophy                                                               |
-^ Nonfluent variant   | Associated with predominantly left posterior frontal-insular 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.
+  * 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 cannot detect changes indicative of FTD.
+  * Individuals with FTD have similar impairments in both semantic (i.e. - naming animals) and letter fluency tasks (i.e. - naming as many words as they can that start with the letter 'F') , due to frontal lobe retrieval deficits.[([[https://pubmed.ncbi.nlm.nih.gov/17201527/|Rascovsky, K., Salmon, D. P., Hansen, L. A., Thal, L. J., & Galasko, D. (2007). Disparate letter and semantic category fluency deficits in autopsy-confirmed frontotemporal dementia and Alzheimer's disease. Neuropsychology, 21(1), 20.]])]
+    * On the other hand, patients with [[geri:dementia:alzheimers|Alzheimer's disease]] are more impaired in semantic than the letter fluency tasks (consistent with impaired access to semantic information due to involvement of the temporal lobes instead)
-===== 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.]])]
+  * There are no approved treatments for FTD. All current treatments are thus off-label and used to manage symptoms of the disease, primarily behavioural symptoms.[([[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.]])]
+  * 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.
+  * For behavioural symptoms (such as disinhibition, impulsivity, repetitive behaviors and eating disorders) may respond to antidepressant class medications (response is thought to be due to loss of serotonergic neurons in FTD[([[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4920050/|Tsai, R. M., & Boxer, A. L. (2014). Treatment of frontotemporal dementia. Current treatment options in neurology, 16(11), 319.]])]), this includes:
+    * [[meds:antidepressants:sari:trazodone|Trazodone]] has very good evidence for the treatment of behavioural symptoms related to FTD.[([[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5761910/|Young, J. J., Lavakumar, M., Tampi, D., Balachandran, S., & Tampi, R. R. (2018). Frontotemporal dementia: latest evidence and clinical implications. Therapeutic advances in psychopharmacology, 8(1), 33-48.]])][([[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.]])]
+    * [[meds:antidepressants:ssri:home|Selective serotonin reuptake inhibitors]] such has [[meds:antidepressants:ssri:citalopram|citalopram]], [[meds:antidepressants:ssri:fluoxetine|fluoxetine]], and [[meds:antidepressants:ssri:sertraline|sertraline]].
+  * 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.
+  * [[meds:dementia:memantine|Memantine]] is not effective.[([[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4920050/|Kishi, T., Matsunaga, S., & Iwata, N. (2015). Memantine for the treatment of frontotemporal dementia: a meta-analysis. Neuropsychiatric disease and treatment, 11, 2883.]])]
+<callout type="danger" title="Do not use acetylcholinesterase inhibitors in FTD or frontal-variant AD" icon="true">
+Evidence suggests cholinesterase inhibitors may actually exacerbate behavioural symptoms. This is because unlike in Alzheimer's dementia, cholinergic neurons are relatively preserved in FTD.[([[https://pubmed.ncbi.nlm.nih.gov/17194818/|Mendez, M. F., Shapira, J. S., McMurtray, A., & Licht, E. (2007). Preliminary findings: behavioral worsening on donepezil in patients with frontotemporal dementia. The American journal of geriatric psychiatry, 15(1), 84-87.]])]
+</callout>
+===== Guidelines =====
+<alert icon="fa fa-arrow-circle-right fa-lg fa-fw" type="success">See also: **[[teaching:clinical-practice-guidelines-cpg|]]**</alert>
+{{page>teaching:clinical-practice-guidelines-cpg#dementia&nouser&noheader&nodate&nofooter}}
+{{page>teaching:clinical-practice-guidelines-cpg#bpsd&nouser&noheader&nodate&nofooter}}
 ===== Resources =====
+== Articles ==
+  * [[https://www.wired.com/story/lee-holloway-devastating-decline-brilliant-young-coder|WIRED: The Devastating Decline of a Brilliant Young Coder]]
 == 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.]]