What is the best approach to manage a 60-year-old female patient with frontotemporal dementia (FTD), presenting with behavioral changes, aggression, apathy, and impaired judgment, who is currently on multiple medications including trazodone (50mg qHS), lorazepam (0.5mg BID), atorvastatin (20mg daily), metoprolol, clonidine, amlodipine, hydrochlorothiazide, acetaminophen, and Advair for comorbidities such as chronic obstructive pulmonary disease (COPD), hypertension, hyperlipidemia, prediabetes, major depressive disorder, anxiety disorder, protein-calorie malnutrition, and nicotine dependence?

Management of Established FTD with Behavioral Symptoms and Polypharmacy

FDG-PET brain imaging is not indicated in this patient with established frontotemporal dementia, as functional neuroimaging should be reserved for cases of diagnostic uncertainty, not for monitoring disease progression or guiding medication decisions in confirmed diagnoses. 1

Why FDG-PET is Not Appropriate Here

The 2020 Brain guidelines explicitly state that functional neuroimaging techniques should be reserved for cases of diagnostic uncertainty despite extensive clinical evaluation and for atypical presentations of early-onset dementia 1. This patient already has an established FTD diagnosis, making FDG-PET inappropriate for the stated purposes of:

• Assessing metabolic patterns for progression monitoring: FDG-PET is a diagnostic tool, not a disease monitoring tool in established FTD 1
• Guiding medication optimization decisions: No evidence supports using FDG-PET results to direct pharmacotherapy choices in confirmed FTD 1

Additionally, the guidelines caution that when non-specific FDG-PET hypometabolism is the only abnormal neuroimaging examination, clinicians should reconsider psychiatric origin 1. In established FTD with progression, FDG-PET adds no actionable information.

The Real Priority: Aggressive Deprescribing

The immediate focus should be systematic medication reduction, particularly targeting benzodiazepines, antipsychotics (if any), and medications without clear ongoing indication in advanced dementia. 1

High-Priority Medications to Deprescribe

Lorazepam 0.5mg BID must be tapered and discontinued given the high risks in dementia patients and lack of efficacy for FTD behavioral symptoms 1:

• Benzodiazepines carry significant fall risk, cognitive worsening, and paradoxical agitation in dementia 1
• Taper by reducing 25% of the dose every 1-2 weeks to avoid withdrawal 1
• Monitor for rebound agitation during taper 1

Trazodone 50mg qHS should be critically evaluated 1:

• While sometimes used for sleep/agitation in dementia, evidence for efficacy in FTD is lacking 2, 3
• Consider continuation only if clear documented benefit on specific target symptoms 1
• If discontinuing, taper over 2-4 weeks with monitoring for worsening behaviors 1

Cardiovascular polypharmacy requires simplification (metoprolol, clonidine, amlodipine, hydrochlorothiazide) 1:

• Four antihypertensive agents suggest over-treatment in advanced dementia 1
• Goals of care should shift toward comfort rather than aggressive cardiovascular risk reduction 1
• Consider reducing to 1-2 agents targeting symptomatic blood pressure control only 1

Atorvastatin 20mg daily should be discontinued 1:

• No mortality benefit in advanced dementia 1
• Prediabetes does not warrant statin therapy, especially in this context 1
• Deprescribing statins in long-term care may reduce mortality by approximately 25% 1

Medications with No Evidence in FTD

There are no FDA-approved medications for frontotemporal dementia 2, 3. The cholinesterase inhibitors and memantine used in Alzheimer's disease have not demonstrated efficacy in FTD and should not be initiated 4, 2.

Evidence-Based Pharmacologic Approaches for FTD Behavioral Symptoms

Selective serotonin reuptake inhibitors (SSRIs) are the only medication class with potential benefit for behavioral symptoms in FTD 2, 3:

• SSRIs may help with disinhibition, compulsive behaviors, and agitation 2, 3
• Consider sertraline 25-50mg daily or citalopram 10-20mg daily as starting doses 2, 3
• Response is variable and should be assessed over 6-8 weeks 3
• Discontinue if no clear benefit after adequate trial 3

Antipsychotics should be avoided or used only for severe agitation posing safety risk 1, 2:

• Very limited efficacy data in FTD 2
• High risk of extrapyramidal symptoms, falls, and mortality in dementia 1
• If absolutely necessary for safety, use lowest dose of quetiapine (12.5-25mg) or risperidone (0.25-0.5mg) 1
• Attempt discontinuation after 3 months, as successful tapering occurs without worsening behaviors in most cases 1

Non-Pharmacologic Management Takes Priority

Non-pharmacologic interventions should be the primary treatment approach for behavioral symptoms in FTD 1:

• Establish predictable daily routines and simplified tasks 4
• Create safe environment with removal of hazards 4
• Caregiver education on FTD-specific behavioral management strategies 3
• Physical activity and structured activities appropriate to cognitive level 1

Appropriate Diagnostic Considerations (Not FDG-PET)

If there were genuine diagnostic uncertainty (which there is not in this established case), the appropriate workup would include 1:

• High-resolution 3D T1-weighted brain MRI with FLAIR sequences to assess for frontotemporal atrophy patterns 1
• CSF or serum neurofilament light chain (NfL) if available with reference values, which distinguishes FTD from psychiatric disorders with high accuracy (AUC 0.93) 1
• Genetic testing for C9orf72, GRN, and MAPT mutations should be strongly considered given the 30-50% familial rate and implications for family members 1, 5

Practical Management Algorithm

1. Immediate: Begin lorazepam taper (25% dose reduction every 1-2 weeks) 1
2. Week 1-2: Discontinue atorvastatin 1
3. Week 2-4: Simplify antihypertensive regimen to 1-2 agents 1
4. Week 4-6: Evaluate trazodone benefit; taper if no clear improvement in target symptoms 1
5. Ongoing: Implement structured non-pharmacologic behavioral interventions 1
6. Consider: SSRI trial (sertraline 25-50mg daily) if behavioral symptoms persist after deprescribing 2, 3
7. Monitor: Functional status, behavioral symptoms, and caregiver burden every 2-4 weeks during medication changes 3

Critical Pitfalls to Avoid

• Do not order FDG-PET for established FTD diagnosis - it provides no actionable information for medication management 1
• Do not continue benzodiazepines in dementia patients - risks far outweigh any potential benefits 1
• Do not use cholinesterase inhibitors or memantine for FTD - no evidence of efficacy 4, 2
• Do not maintain aggressive cardiovascular risk reduction in advanced dementia - goals of care should prioritize comfort and quality of life 1
• Do not abruptly discontinue multiple medications simultaneously - systematic, monitored tapering reduces risk of withdrawal or rebound symptoms 1