Frontotemporal Dementia After the Bruce Willis Effect: What Neurologists Should Revisit

Introduction

Frontotemporal dementia (FTD) is one of the most common causes of young onset dementia and represents a major clinical challenge in neurology, psychiatry, and primary care. Although less prevalent than Alzheimer disease, its impact is often disproportionately severe because it affects individuals during their most productive years, frequently between the ages of 45 and 65. The disease not only compromises cognitive function but also disrupts employment, financial stability, interpersonal relationships, and caregiver well-being. The consequences often extend beyond the patient, creating significant emotional, social, and economic burdens for families and healthcare systems.

FTD encompasses a heterogeneous group of neurodegenerative disorders characterized by progressive degeneration of the frontal and temporal lobes. These brain regions are critical for executive functioning, social cognition, emotional regulation, language, and behavior. As a result, the earliest manifestations of FTD differ markedly from those typically associated with Alzheimer disease. While memory impairment is often the hallmark of Alzheimer disease, patients with FTD frequently present with subtle but progressive changes in personality, behavior, judgment, communication, and social functioning. Episodic memory may remain relatively intact during the early stages, contributing to diagnostic uncertainty and delayed recognition.

The clinical spectrum of FTD includes several distinct syndromes. Behavioral variant frontotemporal dementia, the most common presentation, is characterized by progressive changes in personality and social conduct. Patients may exhibit disinhibition, impulsivity, socially inappropriate behavior, loss of empathy, emotional blunting, apathy, compulsive or repetitive behaviors, and altered eating patterns. These symptoms often lead to significant interpersonal conflict and may be mistaken for psychiatric illness or intentional behavioral changes. Family members frequently report that the individual has become “a different person,” reflecting the profound effects of frontal lobe dysfunction on personality and behavior.

Language predominant forms of FTD, collectively known as primary progressive aphasia, present with gradual deterioration of language abilities. Patients may experience increasing difficulty finding words, constructing sentences, understanding speech, or naming familiar objects. Depending on the underlying subtype, speech may become hesitant and effortful, or language comprehension may progressively decline. These deficits can significantly impair communication long before memory or other cognitive domains become noticeably affected.

One of the greatest challenges in FTD diagnosis is its frequent overlap with psychiatric and behavioral disorders. Early symptoms are often misattributed to depression, anxiety, bipolar disorder, personality disorders, burnout, marital difficulties, substance use, or stress related conditions. Younger patients are particularly vulnerable to misdiagnosis because dementia is often not initially considered in middle aged individuals presenting with behavioral or emotional changes. Consequently, many patients experience prolonged diagnostic journeys, inappropriate treatments, and delayed access to supportive services.

Public awareness of FTD has increased substantially following the widely publicized diagnosis of aphasia and frontotemporal dementia in actor Bruce Willis. Increased awareness has provided valuable opportunities for education regarding young onset dementia and neurodegenerative language disorders. It has also encouraged individuals experiencing concerning symptoms to seek medical evaluation. However, heightened public attention can produce unintended consequences. Some individuals may interpret common age related word finding difficulties or occasional forgetfulness as evidence of a neurodegenerative disease, leading to unnecessary anxiety and healthcare utilization. At the same time, patients with genuine progressive behavioral or language syndromes may still be overlooked if clinicians focus primarily on more familiar psychiatric or cognitive diagnoses.

The appropriate clinical response requires a balanced, evidence based approach. Neurologists and other healthcare professionals should neither dismiss patient concerns nor overdiagnose FTD in individuals with nonspecific symptoms. The primary objective is to identify progressive neurodegenerative syndromes through careful history taking, comprehensive neurological examination, cognitive assessment, and longitudinal observation. Establishing whether symptoms demonstrate a clear pattern of progression is often one of the most important diagnostic considerations.

Differentiating FTD from Alzheimer disease remains a critical aspect of evaluation. Although overlap exists, FTD generally presents with earlier behavioral, executive, or language dysfunction, whereas Alzheimer disease typically begins with episodic memory impairment. Neuropsychological testing can help identify distinct cognitive profiles that support diagnostic differentiation. Structural neuroimaging may reveal focal atrophy involving frontal and temporal regions, while functional imaging can demonstrate characteristic patterns of hypometabolism or hypoperfusion. Advances in biomarker research have further enhanced diagnostic accuracy by helping clinicians distinguish FTD from Alzheimer related pathology and other neurodegenerative conditions.

The expanding role of biomarkers has introduced new opportunities and challenges. Cerebrospinal fluid analysis, molecular imaging, genetic testing, and emerging blood based biomarkers are increasingly being incorporated into diagnostic pathways. However, these tools are most valuable when used to answer specific clinical questions rather than as broad screening tests. Appropriate patient selection, careful interpretation, and integration with clinical findings remain essential to avoid misclassification and unnecessary investigations.

Beyond diagnosis, early recognition of FTD is vital because it enables timely planning and support for patients and caregivers. Although no disease modifying therapies are currently available, interventions focused on symptom management, behavioral strategies, speech and language therapy, occupational therapy, and caregiver education can remarkably improve quality of life. Early diagnosis also facilitates discussions regarding financial planning, legal decision making, driving safety, workplace accommodations, and long term care needs before cognitive and behavioral impairments become severe.

Family support is particularly important because caregivers often experience substantial psychological distress, social isolation, and financial strain. Behavioral symptoms such as disinhibition, aggression, compulsivity, and loss of empathy can place unique burdens on families that differ from those commonly encountered in Alzheimer disease. Multidisciplinary care models involving neurologists, psychiatrists, neuropsychologists, speech language pathologists, social workers, and caregiver support services are therefore essential components of comprehensive management.

As understanding of frontotemporal dementia continues to evolve, clinicians must remain vigilant in recognizing its diverse presentations and distinguishing it from psychiatric disorders and other forms of dementia. The increasing availability of biomarkers and advanced diagnostic tools offers opportunities for earlier and more accurate diagnosis, but clinical judgment remains paramount. Ultimately, the goal is not merely to identify the disease but to provide timely intervention, comprehensive support, and proactive care that addresses the complex needs of both patients and their families before safety concerns and functional crises emerge.

Clinical Spectrum, Genetics, Diagnosis, and Management of Frontotemporal Dementia

Frontotemporal dementia (FTD) is a heterogeneous group of neurodegenerative disorders characterized by progressive degeneration of the frontal and temporal lobes. Unlike many other dementias that primarily affect memory during the early stages, FTD most commonly presents with changes in behavior, personality, language, or executive function. Given its clinical, pathological, and genetic diversity, FTD should be approached as a syndrome-level diagnosis rather than a single disease entity. Accurate diagnosis requires careful phenotypic characterization and, whenever possible, biological clarification through biomarkers, neuroimaging, and genetic testing.

Clinical Spectrum

The clinical manifestations of FTD encompass several syndromes, each reflecting the selective vulnerability of distinct neural networks. The two major clinical presentations are behavioral variant frontotemporal dementia (bvFTD) and primary progressive aphasia (PPA), although overlap with movement disorders and motor neuron disease is increasingly recognized.

Behavioral Variant Frontotemporal Dementia

Behavioral variant FTD is the most common form of FTD and is characterized by progressive deterioration in personality, social conduct, and executive functioning. Early symptoms frequently involve subtle but profound changes in behavior that are often mistaken for psychiatric illness or personality changes.

Core clinical features include behavioral disinhibition, manifested by socially inappropriate comments, impulsive decision making, violation of social norms, or diminished judgment. Many patients develop gross apathy or inertia, characterized by reduced initiative, loss of motivation, and emotional disengagement from previously valued activities. Loss of empathy is particularly characteristic and may manifest as diminished concern for family members, reduced emotional responsiveness, or an inability to appreciate the feelings of others.

Patients commonly exhibit repetitive, ritualistic, or compulsive behaviors. These may include rigid routines, repetitive checking, hoarding, stereotyped movements, or obsessive interests. Dietary and eating changes are also common, including increased preference for sweets and carbohydrates, binge eating, hyperphagia, altered food preferences, and oral exploratory behaviors. Executive dysfunction typically emerges early and affects planning, judgment, problem solving, organization, and cognitive flexibility. In contrast, episodic memory and visuospatial abilities are often relatively preserved during the initial stages of disease, helping distinguish bvFTD from typical Alzheimer disease.

Primary Progressive Aphasia

Primary progressive aphasia represents a group of neurodegenerative syndromes in which progressive language impairment is the predominant presenting symptom. Unlike stroke-related aphasia, language deficits evolve gradually over years and occur in the absence of major behavioral or memory disturbances early in the disease course.

Semantic Variant Primary Progressive Aphasia

Semantic variant PPA is characterized by progressive loss of semantic knowledge, resulting in impaired understanding of words, objects, faces, and concepts. Speech remains fluent and grammatically intact, but content becomes increasingly empty due to declining vocabulary and word comprehension. Patients may substitute general terms for specific objects and demonstrate profound difficulty naming familiar items.

Nonfluent or Agrammatic Primary Progressive Aphasia

Nonfluent or agrammatic PPA presents with effortful, halting speech and impaired grammatical construction. Speech production becomes increasingly laborious and may be accompanied by apraxia of speech, resulting in distorted articulation and inconsistent speech errors. Sentences become simplified and grammatically incomplete, while comprehension of complex syntax may also decline.

Logopenic Primary Progressive Aphasia

The logopenic variant requires special consideration because it frequently reflects underlying Alzheimer pathology rather than frontotemporal lobar degeneration. Patients exhibit impaired word retrieval, frequent pauses during speech, and difficulty repeating phrases or sentences. Because of its strong association with Alzheimer disease, amyloid and tau biomarkers may provide important diagnostic clarification and influence treatment considerations.

Overlap Syndromes

FTD exists on a spectrum that frequently overlaps with other neurodegenerative disorders. Some patients develop features of motor neuron disease, progressive supranuclear palsy, corticobasal syndrome, or parkinsonism. Recognition of these overlap syndromes is essential because they influence prognosis, management, and counseling.

FTD associated with motor neuron disease carries a particularly aggressive clinical course and generally confers a poorer prognosis. Clinicians should routinely assess for dysphagia, respiratory symptoms, muscle weakness, fasciculations, pseudobulbar affect, and signs of upper or lower motor neuron dysfunction. Early advance care planning and comprehensive caregiver support become especially important in these patients.

Pathology and Genetics

The pathological basis of FTD is highly diverse. The three major pathological subtypes are frontotemporal lobar degeneration with tau pathology (FTLD-tau), frontotemporal lobar degeneration with TAR DNA-binding protein 43 pathology (FTLD-TDP), and frontotemporal lobar degeneration with fused in sarcoma pathology (FTLD-FUS).

Although certain clinical syndromes may suggest underlying pathology, phenotype alone cannot reliably predict pathological subtype in individual patients. Semantic variant PPA is frequently associated with TDP-43 pathology, while nonfluent PPA is often linked to tau pathology. However, substantial overlap exists, and exceptions are common.

Genetic factors play a significant role in FTD, particularly among individuals with early onset disease or a positive family history. The three most important genes associated with familial FTD are C9orf72, GRN, and MAPT.

Expansions in the C9orf72 gene represent the most common genetic cause of familial FTD and amyotrophic lateral sclerosis. These expansions may result in isolated FTD, isolated ALS, or combined FTD-ALS syndromes and can be associated with prominent psychiatric symptoms.

Mutations in the GRN gene lead to progranulin deficiency and are most commonly associated with TDP-43 pathology. Clinical presentations may vary considerably, even among affected members of the same family.

Mutations in MAPT directly affect tau protein biology and are associated with tau pathology. Patients with MAPT mutations often develop behavioral and cognitive symptoms at relatively young ages.

Because genetic findings have notable implications for family members, reproductive decisions, psychological well-being, research participation, and future access to targeted therapies, genetic counseling should be offered to all patients diagnosed with an FTD spectrum disorder. Importantly, a negative family history does not exclude a genetic etiology. Genetic testing should ideally occur within a specialized neurogenetics framework, and predictive testing of asymptomatic relatives should follow formal counseling protocols.

Diagnostic Approach

Accurate diagnosis begins with a thorough clinical history, with particular emphasis on collateral information obtained from informants. Patients with bvFTD often lack insight into their symptoms, making reports from spouses, adult children, coworkers, employers, or caregivers essential.

Clinicians should specifically inquire about changes in financial judgment, inappropriate social behavior, diminished empathy, sexual disinhibition, compulsive habits, alterations in eating behavior, binge eating, apathy, neglect of personal hygiene, workplace difficulties, unsafe driving, and violations of interpersonal boundaries.

Neuropsychological Assessment

Comprehensive neuropsychological testing plays a central role in diagnosis. Evaluation should assess executive function, language, social cognition, memory, visuospatial skills, attention, processing speed, and psychiatric influences on cognition.

Brief cognitive screening instruments may fail to detect early bvFTD because orientation and simple memory tasks often remain intact while social judgment, executive functioning, and behavioral regulation deteriorate. Specialized testing of social cognition and executive abilities may therefore provide critical diagnostic information.

Neuroimaging

Structural neuroimaging with magnetic resonance imaging is an essential component of evaluation. Typical findings include atrophy involving the frontal lobes, anterior temporal regions, insula, and other cortical areas. Patterns may be symmetric or asymmetric depending on the underlying syndrome.

Functional imaging with fluorodeoxyglucose positron emission tomography may be particularly valuable when MRI findings are subtle or inconclusive. FDG-PET can demonstrate characteristic patterns of frontal and temporal hypometabolism and may help differentiate FTD from Alzheimer disease and primary psychiatric disorders.

When Alzheimer disease remains a diagnostic consideration, particularly in patients with logopenic PPA or atypical early onset dementia, amyloid PET imaging, cerebrospinal fluid biomarkers, or validated plasma Alzheimer biomarkers may provide important clarification.

Biomarkers

Biomarkers are increasingly incorporated into the diagnostic evaluation of neurodegenerative disease. Neurofilament light chain serves as a marker of neuronal injury and may support the presence of active neurodegeneration. Although elevated levels can help distinguish neurodegenerative disease from some psychiatric conditions, the marker lacks specificity for FTD.

Plasma phosphorylated tau biomarkers, particularly p-tau217, are more useful for identifying or excluding Alzheimer pathology than for confirming FTD. Similarly, current tau PET imaging techniques are most effective for detecting Alzheimer-type tau pathology and remain less reliable for many forms of FTLD-tau.

Differential Diagnosis

The differential diagnosis of FTD is broad and requires careful consideration of neurodegenerative, psychiatric, metabolic, infectious, autoimmune, and structural conditions.

Behavioral variant FTD is frequently mistaken for psychiatric disease because of its prominent behavioral manifestations. Features that should raise suspicion for bvFTD include late onset psychiatric symptoms, progressive functional decline, loss of empathy, impaired social cognition, compulsive behaviors, poor insight, and characteristic neuroimaging abnormalities.

Nevertheless, clinicians should avoid prematurely attributing symptoms to neurodegeneration. Depression, bipolar disorder, substance use disorders, traumatic brain injury, sleep disorders, autism spectrum traits, medication effects, and functional neurological conditions may produce overlapping features.

Alzheimer disease remains a major differential diagnosis. While typical Alzheimer disease begins with episodic memory impairment, FTD more often presents with behavioral or language dysfunction. However, atypical Alzheimer variants can mimic FTD through language, executive, behavioral, or visuospatial presentations. Biomarker confirmation is becoming increasingly important as disease-specific therapies emerge.

Additional conditions that should be considered include Lewy body disease, Huntington disease, vascular cognitive impairment, normal pressure hydrocephalus, autoimmune encephalitis, neurosyphilis, HIV-associated neurocognitive disorder, vitamin B12 deficiency, thyroid dysfunction, obstructive sleep apnea, and medication toxicity. A comprehensive evaluation should always exclude potentially reversible or treatable contributors before establishing a diagnosis of FTD.

Management Principles

Management of FTD requires a multidisciplinary approach focused on symptom management, safety, caregiver support, and preservation of quality of life. Because no disease-modifying therapies are currently approved for most forms of FTD, treatment is largely supportive and individualized.

Education is a critical first step. Families must understand that many behaviors arise from neurodegenerative processes rather than intentional misconduct. At the same time, practical strategies are necessary to reduce harm and maintain safety.

Early discussions should address driving safety, firearm access, medication management, financial oversight, online spending, employment concerns, sexual disinhibition, wandering risk, choking hazards, substance use, and caregiver burden.

Nonpharmacologic Interventions

Nonpharmacologic approaches represent the foundation of symptom management. Structured daily routines, environmental modifications, reduction of behavioral triggers, simplified decision making, supervision of finances and medications, and caregiver coaching can merkedly improve daily functioning.

Occupational therapy may assist with adaptive strategies and maintenance of independence. Speech-language therapy is essential for patients with language impairment, while social work services can help families navigate legal, financial, and caregiving challenges.

Palliative Care

Palliative care should be integrated early in the disease course rather than reserved for advanced stages. Early involvement can facilitate discussions regarding goals of care, feeding decisions, advance directives, behavioral crises, symptom management, and caregiver support. This proactive approach often improves quality of life for both patients and families.

Speech-Language Therapy

Speech-language therapy plays a particularly important role in primary progressive aphasia. Interventions should focus on maximizing communication and maintaining social participation for as long as possible. Strategies may include communication partner training, scripted conversations, communication notebooks, augmentative and alternative communication devices, and compensatory techniques tailored to the patient’s language deficits. Swallowing function should also be monitored when clinically indicated, particularly in patients with progressive motor involvement.

As advances in biomarker science, genetics, and targeted therapeutics continue to evolve, the diagnosis and management of FTD are becoming increasingly precise. A comprehensive, patient-centered approach that integrates clinical phenotyping, biological characterization, multidisciplinary care, and proactive family support remains essential for optimizing outcomes across the frontotemporal dementia spectrum.

Medication Use and Safety

No medication has been proven to modify the course of FTD. Pharmacotherapy should target specific symptoms, use measurable goals, and be reassessed regularly.

SSRIs may be considered for disinhibition, compulsive behavior, irritability, anxiety, depressive symptoms, hyperorality, or repetitive behaviors. Options commonly used in practice include sertraline, citalopram, escitalopram, fluvoxamine, fluoxetine, and paroxetine, although comparative evidence is limited. Clinicians should monitor for hyponatremia, falls, bleeding risk when combined with antiplatelets or anticoagulants, QT prolongation with susceptible agents, sexual dysfunction, gastrointestinal effects, drug interactions, and serotonin syndrome when combined with other serotonergic drugs.

Trazodone may help sleep disruption, agitation, irritability, or eating-related behavioral symptoms in some patients. It should be used cautiously in patients at risk for orthostatic hypotension, sedation, falls, QT prolongation, priapism, and polypharmacy-related adverse effects.

Antipsychotics should be reserved for severe agitation, psychosis, aggression, dangerous impulsivity, or distressing symptoms that have not responded to safer approaches. They should be prescribed at the lowest effective dose for the shortest feasible duration, with documentation of the target symptom and monitoring for sedation, falls, parkinsonism, akathisia, tardive dyskinesia, metabolic effects, QT prolongation, stroke risk, neuroleptic malignant syndrome, and increased mortality in dementia-related psychosis. Quetiapine is sometimes selected when parkinsonism is present, but evidence remains limited and use is off-label.

Cholinesterase inhibitors should not be used routinely for true FTD. They may worsen disinhibition, agitation, or compulsive behavior in some patients. Memantine is also not supported for routine FTD treatment. These drugs may be reasonable only when Alzheimer pathology is suspected or confirmed, or when the clinical syndrome is mixed.

Benzodiazepines and anticholinergic drugs should generally be avoided when possible. Benzodiazepines may worsen sedation, falls, disinhibition, confusion, and respiratory risk. Anticholinergic drugs can worsen cognition, urinary retention, constipation, dry mouth, blurred vision, and delirium risk.

Anti-amyloid monoclonal antibodies approved for early Alzheimer disease are not FTD therapies. They require Alzheimer disease biology, appropriate disease stage, MRI screening and monitoring, and careful review of amyloid-related imaging abnormality risk. A patient with an FTD-like syndrome should not be referred for these drugs unless Alzheimer pathology is demonstrated and the patient otherwise meets Alzheimer-specific treatment criteria.

Table 1. Practical Diagnostic Review for Suspected FTD

Clinical issue	What to revisit	Practical implication
bvFTD vs psychiatric disease	Do not rely only on patient report or brief cognitive screening	Obtain informant history, neuropsychology, MRI, and consider FDG-PET or biomarkers when unclear
PPA variant	Logopenic PPA often suggests Alzheimer pathology	Consider amyloid/tau biomarkers before labeling as FTLD
Genetic testing	Family history may be absent despite genetic disease	Offer genetic counseling and testing to diagnosed FTD patients
NfL	Marker of neurodegeneration, not FTD-specific	Useful for progression or neurodegenerative vs psychiatric distinction, but not diagnostic alone
Plasma p-tau217 and amyloid biomarkers	Best for Alzheimer pathology	Helpful when distinguishing AD from FTD or determining Alzheimer therapy eligibility
MRI and FDG-PET	Pattern recognition matters	Look for frontal, anterior temporal, insular, asymmetric, or AD-like patterns
Motor features	May indicate FTD-MND, PSP, CBS, or mixed disease	Screen for dysphagia, respiratory symptoms, falls, gaze palsy, rigidity, apraxia, and weakness
Caregiver burden	Often the dominant clinical problem	Address safety, finances, driving, legal planning, respite, and palliative care early

Table 2. Medication Safety Review in FTD

Drug class	Possible role	Key cautions
SSRIs	Disinhibition, compulsions, irritability, anxiety, hyperorality, repetitive behaviors	Hyponatremia, falls, GI effects, bleeding risk, QT risk with selected agents, sexual dysfunction, serotonin syndrome
Trazodone	Sleep disruption, agitation, irritability, eating-related symptoms	Sedation, orthostasis, falls, QT risk, priapism
Atypical antipsychotics	Severe aggression, psychosis, dangerous behavior after safer measures fail	Increased mortality warning in dementia-related psychosis, stroke risk, EPS, sedation, falls, metabolic effects, QT prolongation
Cholinesterase inhibitors	Generally avoid in true FTD	Limited efficacy, possible behavioral worsening; consider only if AD pathology or mixed disease is suspected
Memantine	Generally avoid routine use	Randomized trial evidence does not support routine benefit in FTLD
Benzodiazepines	Rare short-term rescue use only	Sedation, falls, paradoxical disinhibition, confusion, respiratory risk
Anticholinergics	Avoid when possible	Cognitive worsening, constipation, urinary retention, blurred vision, delirium
Anti-amyloid monoclonal antibodies	Not FTD therapy	Only for eligible Alzheimer disease with confirmed amyloid pathology and required MRI safety monitoring

The “Bruce Willis Effect” in Practice

The Bruce Willis announcement made FTD more visible, but awareness alone is not a diagnostic tool. A public figure can reduce stigma and help families recognize symptoms, but media attention can also oversimplify the disease. Aphasia is not synonymous with FTD. FTD is not a single disorder. There is no simple blood test that confirms most cases. There is no approved disease-modifying treatment.

Clinicians should respond to increased awareness by improving triage. A patient with isolated age-consistent word-finding difficulty does not need an FTD label. A patient with progressive language impairment, loss of social judgment, new disinhibition, unexplained apathy, compulsive behavior, late-onset psychiatric symptoms, or loss of empathy deserves a structured neurodegenerative evaluation.

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