Alexander Z. Harris, MD, PhD, is Resident, Department of Internal Medicine, New York Hospital Medical Center of Queens, and Weill Medical College of Cornell University, Queens, New York. Dimitry Francois, MD, is Geriatric Fellow, Weill Medical College of Cornell University, Westchester Division, New York. Nahla Mahgoub, MD, is Instructor in Psychiatry, Weill Medical College of Cornell University, Westchester Division.
Dr. Harris; Dr. Francois; and Dr. Mahgoub have disclosed no relevant financial relationships.
Address correspondence to: Nahla Mahgoub, MD, 21 Bloomingdale Road, White Plains, New York, 10605; e-mail: email@example.com; firstname.lastname@example.org.
Mrs. A, a 72-year-old woman without prior psychiatric history, was brought to the hospital after she threatened to commit suicide, which was shortly after her son moved her from her apartment to an assisted-living facility. The patient expressed great unhappiness with her new living situation, complaining that she was the youngest person there and the facility lacked activities appropriate for her age, including “exercise and disco dancing.”
Further evaluation revealed that throughout the past 8 months, she had caused several car accidents by driving recklessly and had neglected daily life activities, including cooking, paying bills, and house cleaning. The patient reported that she drove over a woman’s foot twice and then left the scene. Back at her home, every surface was covered with clutter, and trash was strewn throughout the floor. There were checks made out in response to scams, unpaid bills, and burned pots. The patient was reportedly banned from a local department store because of a pattern of buying and returning items daily. This behavior had worsened throughout the past few months.
Outpatient neurological evaluation was unremarkable, except for slow wave activity consistent with mild cerebral dysfunction on EEG. The patient consulted with a psychiatrist who started her on mirtazapine 7.5 mg daily and memantine 5 mg twice daily. Her son recognized that her recent behavior represented a significant change in her ability to function, and so he moved her to an assisted-living facility.
The differential diagnosis included:
Focal organic brain lesions leading to executive dysfunction.
Depression with executive dysfunction.
The patient was admitted for further evaluation of her suicidal ideation and because of the causes of deterioration in her functioning. She was disheveled, labile, and easily tearful. She was distraught over her inability to have a sugar substitute and cookies. She was disinhibited, volunteering that “she used to have great sex.” She hoarded more than 20 disposable cups on her dresser and talked about returning to independent living. There was no psychomotor retardation or agitation. She denied suicidal thoughts. No neurovegetative symptoms were reported. She denied history of head trauma and substance abuse. She also denied family history of psychiatric illness. Her medical history was insignificant.
What Diagnostic Tests Would You Consider?
Mini-mental state examination.
Laboratory tests, including folate and vitamin B12 levels, urine analysis, and toxicology.
All of the above.
Her physical and neurological examinations were unremarkable. Her speech was normal in rate and volume, and she did not have difficulty in word-finding or in naming objects. A Folstein mini-mental state examination (MMSE) was scored at 27 out of 30 items. She was oriented to time, place, and person. Registration and free recall were intact. Repetition, comprehension, and writing were within normal limits. She was able to copy a figure of interlocking pentagons. However, she was not able to do simple tasks that require attention and concentration, such as making serial 7s and spelling. There was no evidence of delusions or perceptual disturbances. Her judgment and insight were impaired.
The consultant neurologist did not find any focal neurological signs. Brain magnetic resonance imaging (MRI) with contrast indicated mild cerebral atrophy. She scored well on both verbal and visual memory items on the Dementia Rating Scale. However, the Draw-a-Clock test showed poor spatial planning, and she placed the hands of the clock inaccurately. The Mattis Dementia Rating Scale was notable for normal scores in the memory domain and poor performance in the conceptualization and initiation/perseveration domain; she failed in both tasks of motor sequencing and category switching. Thyroid, renal, and liver function tests, complete blood count, and blood chemistry were within normal limits. Folate and vitamin B12 levels revealed no deficiencies. Urine toxicology and urinalysis were negative.
Frontotemporal Dementia (FTD)
The patient’s symptoms were consistent with frontotemporal dementia (FTD). FTD is a relatively common but underdiagnosed neurodegenerative dementia.1 FTD accounts for 6% to 25% of all dementias and is the fourth most common progressive dementia after Alzheimer’s disease (AD), vascular dementia, and Lewy body dementia.1
The average age of FTD onset is 45 to 65 years.2 Patients with FTD initially present with noncognitive symptoms, such as personality and behavioral changes, with relatively sparing of memory.1,2 The initial symptoms are insidious and often overlap with those of AD, depression, mania, obsessive-compulsive disorder, and personality disorder.1 It is common for FTD patients to receive other diagnoses on the basis of presenting symptoms, such as AD when cognitive and language symptoms dominate the clinical picture, or bipolar disorder when personality and behavioral changes are prominent.1 Cognitive deficits in patients with FTD pertain primarily to impairment of executive function.2 Many commonly used screening tests for dementia, including MMSE, fail to detect early signs of frontal lobe dysfunction.1 Nevertheless, a combination of clinical history, mental status examination, neuropsychological testing, and neuroimaging may guide the diagnosis.1,2
In our patient, we have discussed three sets of diagnostic challenges posed by FTD. First, its pronounced behavioral changes may initially obscure subtle cognitive deficits. Second, mood lability, often a sign of FTD, may suggest a bipolar disorder. Third, the high prevalence of idiopathic depression may bias clinicians against making the diagnosis when FTD patients present with symptoms and signs of depression.
The patient’s symptoms include insidious onset of progressive mood lability, disinhibition, perseveration, reckless behavior, lack of social judgment, self-neglect, executive dysfunction, and poor insight. She, however, had relatively spared memory.
The mood lability and disinhibition were pronounced to the point that they could be mistaken for mania. However, manic patients report decreased need for sleep, overproductive speech, flight of ideas, and increased goal-directed activities, which were not exhibited by this patient. Her self-neglect and tearfulness suggested a depressive syndrome. Depression with executive dysfunction (DED) was a diagnostic possibility (see Table 1, page 971). However, what makes DED a less likely diagnosis in this patient is the absence of psychomotor retardation and loss of interest in activities.
Table 1. Clinical Manifestations and Cognition in Frontotemporal Dementia, Depression with Executive Dysfunction, Bipolar Disorder, and Alzheimer’s Disease6–10
The absence of memory impairment makes the diagnoses of AD and vascular dementia unlikely because memory loss is an essential component of these syndromes. Further, difficulty in name and word finding is frequently seen in AD.1 Vascular dementia is differentiated by sudden onset and evidence of focal neurological deficits.2
Deficits in executive functions in the absence of memory loss suggest a frontal lobe syndrome.1,2 Common causes of a frontal lobe syndrome include brain tumors, abscesses, and strokes. However, the onset of symptoms in these conditions is acute or subacute and imaging is often diagnostic.1
The insidious onset and progressive course of illness in this patient suggest a neurodegenerative process. Frontotemporal lobar degeneration (FTLD) is a group of dementia syndromes that affect frontal and temporal lobes.2 The Neary Criteria defined three major subtypes of FTLD, based on the regions of brain involvement and the prominent clinical symptomatology.1–4 These include a frontally predominant syndrome (ie, FTD), a temporally predominant syndrome (semantic dementia, or SD), and a left frontally predominant syndrome (primary progressive aphasia, PPA).1–4 The distinction between these syndromes is clinically relevant (see Table 2, page 972).
Table 2. Clinical Manifestations of FTD, Semantic Dementia (SD), and Primary Progressive Aphasia (PPA)1,2
Some may argue against the diagnosis of the late age of onset, although cases have been reported with an onset as young as 21 years and as old as 85 years.5
In this patient, mirtazapine and memantine were increased to 15 mg daily. She remained labile, disorganized, and perseverative. Risperidone 0.25 mg twice a day was added to her regimen, and she became less labile. However, her perseveration, hoarding, and poor personal hygiene were noticeable. Her insight remained superficial at best, and she was discharged back to the assisted-living facility.
In summary, FTD is an early-onset cognitive disorder associated with deficits in executive function that is disproportionate to memory, coupled with personality and behavioral changes. The noncognitive symptoms of FTD are usually prominent and can mask the cognitive deficits, particularly during the initial stages of illness. Therefore, patients in early stages of FTD may receive a different psychiatric diagnosis. However, consensus diagnostic criteria and a high index of suspicion in younger patients may assist earlier recognition of FTD (see Sidebar).
Consensus Diagnostic Criteria for FTD Diagnosis1–3
Core Diagnostic Features
- Insidious onset and gradual progression
- Early decline in social interpersonal conduct
- Early impairment in regulation of personal conduct
- Early emotional blunting
- Early loss of insight
Supportive Diagnostic Features
- Behavioral disorder: decline in personal hygiene, mental rigidity, distractibility, hyperorality, perseverative, and stereotyped behaviors
- Speech and language disorder: perseveration and stereotyped speech, echolalia, and mutism
- Physical signs: primitive reflexes, incontinence, tremors, and rigidity
- Investigation: frontal lobe abnormalities on neuropsychological evaluation. Brain imaging studies related to frontal and temporal lobes.
- Agronin ME, Malette GJ. Principles and Practice of Geriatric Psychiatry. Philadelphia, PA: Lippincott Williams & Wilkins; 2006:319–332.
- Sadavoy J, Jarvik LF, et al. Comprehensive Textbook of Geriatric Psychiatry. Norwich, NY: Bytheway Publishing Services; 2004:545–576.
- Neary D, Snowden JS, Gustafson L, et al. Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology. 1998;51:1546–1554.
- Snowden J, Neary D, Mann DM. Frontotemporal dementia. Br J Psychiatry. 2002;180(2):140–143. doi:10.1192/bjp.180.2.140 [CrossRef]
- Farmer J, Grossman M. Frontotemporal dementia: an overview. Alzheimer’s Care Quarterly. 2005;6(3):225–232.
- Alexopoulos GS, Kiosses DN, Murphy C, Heo M. Executive dysfunction and the course of geriatric depression. Biol Psychiatry. 2005;58(3):204–210. doi:10.1016/j.biopsych.2005.04.024 [CrossRef]
- Alexopoulos GS, Kiosses DN, Klimstra S, Kalayam B, Bruce ML. Clinical presentation of the “depression-executive dysfunction syndrome” of late life. Am J Geriatr Psychiatry. 2002;10(1):98–106.
- Gunning-Dixon F, Murphy C, Alexopoulos GS, Majcher-Tascio M, Young RC. Executive dysfunction in elderly bipolar manic patients. Am J Geriatr Psychiatry. 2008;16(6):506–512. doi:10.1097/JGP.0b013e318172b3ec [CrossRef]
- Lockwood KA, Alexopoulos GS, van Gorp WG. Executive dysfunction in geriatric depression. Am J Psychiatry. 2002;159(7):1119–1126. doi:10.1176/appi.ajp.159.7.1119 [CrossRef]
- Goodwin FK, Jamison KR. Manicdepressive Illness/Bipolar Disoders and Recurrent Depression. Oxford, England: Oxford University Press; 2007:273–322.
- Rosness TA, Haugen PK, Passant U, Engedal K. Frontotemporal dementia: a clinically complex diagnosis. Int J Geriatr Psychiatry. 2008;23(8):837–842. doi:10.1002/gps.1992 [CrossRef]
Clinical Manifestations and Cognition in Frontotemporal Dementia, Depression with Executive Dysfunction, Bipolar Disorder, and Alzheimer’s Disease6–10
|Condition||Clinical Manifestations (noncognitive symptoms)||Neuropsychological Testing|
|Frontotemporal Dementia||Mood lability, childish behavior, impulse buying, use of catch phrases, inappropriate social behavior and sexual remarks, rudeness, impatient, careless driving, excessive spending or hoarding, inappropriate joking, perseverative routines, compulsive roaming, preference for sweets, excessive food intake, hyperorality, self-neglect, disinterest in the immediate family, or others, disturbances in planning, sequencing, organizing, and abstracting.||Perseveration on the Wisconsin Card Sorting task, disorganization on clock drawing, and poor picture arrangement on Wechsler Adult Intelligence Scale, visuospatial function is relatively spared, reduced verbal fluency, orientation, learning skills, and comprehension are relatively spared, recall is mildly impaired because of inattention.|
|Depression with Executive Dysfunction||Patients meet DSM-IV criteria for major depression, often have psychomotor retardation, loss of interest in activities, suspiciousness, disability greater than expected based on the severity of their depression, and mild vegetative syndrome.||Reduced verbal fluency, impaired visual naming, poor performance on problemsolving tasks, poor retrieval.|
|Bipolar Disorder||Persistently elevated or irritable mood lasting at least 1 week with three or more of the following: grandiosity, decreased need for sleep, overproductive speech, flight of ideas, distractibility, increased goal-directed activities, and psychomotor agitation.||Impaired executive function, deficits in attention and visual memory, deficits in the acquisition of new information, poor performance on tasks of initiation, concept formation, and set shifting, language is spared.|
|Alzheimer’s Dementia||Memory loss since early stages, gradual development of deficits in language, praxis, gnosis, and executive function, inability to perform daily living activities, neuropsychiatric symptoms when present: depression, apathy, social withdrawal, agitation, and paranoia.||Executive dysfunction; short-term memory deficits, difficulty in word finding, recall is poor, impaired visuospatial abilities, aphasia, apraxia, or agnosia.|
Clinical Manifestations of FTD, Semantic Dementia (SD), and Primary Progressive Aphasia (PPA)1,2
|Core Diagnostic Features||Personality and behavioral changes with relatively spared memory; impaired executive function||Impaired understanding of word meaning and object identity||Disorder of expressive language with relative sparing of memory|
|Initial Presentation||Noncognitive symptoms; behavior and personality changes||Difficulty in naming objects (anomia)||Difficulty in word finding|
|Speech||Reduced verbal fluency; perseveration and stereotyped speech||Fluent, empty; intact grammatical structure||Nonfluent; poor grammatical structure; phonemic paraphasias|
|Behavioral Changes||Personality changes; lack of empathy; disinhibition, apathy, and stereotypy; lack of social awareness, carelessness, and self-neglect; mood lability; verbal and/or behavioral perseveration||Similar to those of FTD||Appear late in the disease course|
|Other Manifestations||Frontal release signs such as a positive glabellar sign and grasp; extrapyramidal signs; incontinence||Prosopagnosia (failure to recognize familiar faces) and agnosia (failure to recognize objects)||Difficulty in reading and writing|
|Brain Imaging||Atrophy of the frontal lobes is typically symmetrical and bilateral||Atrophy is bilateral and predominant in the anterior temporal lobes||Atrophy is asymmetric and prominently evident in the left frontotemporal lobes|