A Case of Atypical Early-Onset Dementia in a 54-year-old Female
Mrs. P, a 54-year-old Caucasian female, was seen by her primary care provider five years ago with a complaint of “memory problems.” She noted episodes of forgetfulness from as early as age 46. Mrs. P’s husband had noted changes in both her personality and memory. He reported out-of-character use of profanity and a gradual onset of apathy. She had progressively become less attentive to daily routines at home. Mrs. P complained of episodes where she had forgotten the route home, and reported difficulty remembering steps in routine tasks she had performed repeatedly for years.
Further evaluation revealed a maternal family history of early-onset dementia. The patient’s mother was diagnosed with Alzheimer’s disease and was placed in long-term care at an early age. Mrs. P initially attributed her changes in mood and cognition to menopause in her early 40s. Her medical history was significant for degenerative changes of the spine and mitral valve prolapse. Mrs. P denied any history of psychiatric hospitalizations, psychiatric treatments, head injury, or substance abuse. She has been married for 38 years. She completed nine years of school and never worked outside the home. She has one adult son and two grandchildren. Mrs. P’s husband is disabled and relies upon her as his primary caregiver.
In her early 50s she was referred for neuropsychological testing, which revealed that her earliest symptoms were forgetting names, familiar neighbors, and close relatives. Mrs. P was surprised to have forgotten a familiar recipe for making biscuits that she had used for years by memory. She also reported episodes of forgetting to give her husband his medications. Full scale IQ was measured at 89. A Folstein Mini-Mental State Examination was scored at 29 out of 30 items. An evaluation by Neuropsychology initially diagnosed depression with no cognitive deficits. Two interval exams by Neuropsychology over a two-year span revealed cognitive deterioration with evidence of frontal lobe involvement. At the age of 53, Mrs. P was referred to a University-affiliated outpatient psychiatric clinic for further evaluation.
Frontotemporal lobar dementia (FTLD) is a progressive dementia characterized by early onset and progressive deterioration of the patient’s personality and social functioning. Early predominant symptoms vary among patients and are described within three distinct syndromes: frontotemporal dementia, progressive nonfluent aphasia, and semantic dementia. Frontotemporal lobar dementia is thought to be the third most common nonvascular cause of cortical dementia.1 Alzheimer’s and Lewy body dementias are the most common causes of nonvascular cortical dementia. Frontotemporal lobar dementia is thought to be equivalent in prevalence to Alzheimer’s disease in patients under 65 years of age.2 Along with early age of onset, typical findings in patients with FTLD include early behavioral changes, early emotional blunting, and early loss of insight. Supportive features include a decline in executive functioning and a relatively well-preserved short-term memory. In contrast to Alzheimer’s disease, FTLD is diagnosed by a consensus criterion.3 The prevalence of FTLD is estimated to be 15 per 100,000.4
Some research indicates that many patients with FTLD meet the criteria for diagnosis of Alzheimer’s dementia.5 It has been suggested that the best way to distinguish these separate diagnostic entities is to be familiar with the FTLD consensus criteria for diagnosis.6 Early behavioral and language changes in a younger patient coupled with a relatively intact episodic memory are examples of findings that can distinguish FTLD from Alzheimer’s disease (Table).
Patients are often diagnosed during mid-course of their illness due to the early and slow onset of FTLD. Patients with FTLD may also develop a language disorder characterized by a failure to retrieve words (anomia), a loss of grammatical syntax (agrammatism), idiosyncratic word usage, and a transposition of sound in a word (phonemic paraphasia). Examples of anomia include saying “watcher” instead of “washer” and applying the word “clothes” instead of saying “pants.” Agrammatism is illustrated by use of the phrase “box fell down” instead of “the box fell on the floor.” An example of phonemic paraphasia would be using the term “cubunker” instead of “cucumber.”
Behavioral problems range from inappropriate social conduct to observed abnormal behaviors. Intrusiveness, disinhibition, and lack of empathy are behaviors usually noted by family members. Aggression, pacing, passivity, wandering, apathy, poor hygiene, impaired concentration, and repetitive behaviors are often observed in the middle and late stages of FTLD. Patients with FTLD often find difficulty in adapting to new situations and cope by adopting rigid routines. Insight and acknowledgment of abnormal symptoms along with functional implications of the disease diminish in the early stages of FTLD. Apathy and denial of impaired behaviors progress over time.
Each of the three syndromes may vary anatomically.7 In frontotemporal dementia, there is prominent involvement in the frontal lobes. Atrophy of the frontal lobes is typically symmetrical and bilateral. In progressive nonfluent aphasia, atrophy is asymmetric and prominent in the left frontotemporal lobes. In semantic dementia, atrophy is bilateral and predominantly evident in the anterior temporal lobes.
While FTLD encompasses three distinct syndromes, there is often overlap in clinical findings as the disease progresses. Progressive nonfluent aphasia is a disorder of expressive language with effortful speech, sound errors, syntax errors, and word-finding difficulties.8 Word comprehension is intact, and the disorder occurs in the absence of other abnormal cognitive findings. Patients with progressive nonfluent aphasia will also have difficulty with reading and writing. Behavioral changes typically emerge later.
In semantic dementia, naming objects and word comprehension is severely impaired.9 This disorder occurs with preservation of repetitive verbal skills and ability to write words that are dictated. The ability to read aloud is also preserved. In semantic dementia, perceptual disorders such as prosopagnosia and/or associative agnosia are present. Prosopagnosia is a failure to recognize familiar faces. Associative agnosia is a failure to recognize objects. Characteristic behavioral problems include loss of empathy, rigid routines, and focused preoccupations (eg, works on a hobby all day rather than eating or performing chores).
The increased availability and employment of neuroimaging is valuable in the early detection of FTLD.10 Increased knowledge of FTLD has prompted more interest in researching the incidence and prevalence of early-onset dementias.11 The actual numbers of FTLD cases may not be increasing, but rather the disorder is likely detected earlier with increased awareness of the condition in younger populations, along with increased utilization of neuroimaging studies.12 Involving Neurology and Psychiatry services early in treatment can help symptomatically. Given the younger age of patients with FTLD, the impact of managing the progression of the disease is similar to that of Huntington’s chorea or amyotrophic lateral sclerosis. As with other dementias, FTLD is irreversible, and treatment is focused on symptomatic relief. Neuroleptic and antidepressant medications can relieve symptoms associated with aggression and mood disturbances. Neuroleptics should be used with caution since patients with FTLD are more susceptible to akathisia and symptoms of parkinsonism.13 Some clinical researchers suggest that patients with FTLD are vulnerable to decreased levels of serotonin in the brain.14 Results of limited trials of selective serotonin reuptake inhibitors in FTLD suggest that antidepressants may be helpful for mood symptoms.15 Thus far, a role for acetylcholinesterase inhibitors in the treatment of FTLD has not been established. There appears to be no clear association between FTLD and deficiencies of available acetylcholine in the brain.16 Antiparkinsonian medications have been used in treating FTLD, with some short-term efficacy in treating perseveration and improving executive functioning.17
In summary, FTLD is an early-onset cognitive disorder identified by behavioral changes that distinguish it from Alzheimer’s and other dementias that typically manifest later in life. Frontotemporal lobar dementia is a diagnosis of exclusion based on consensus criterion. Familiarity with this core criteria and a high index of suspicion in younger patients with cognitive impairments can facilitate earlier detection of FTLD.
OUTCOME OF THE CASE PATIENT
A psychiatric evaluation revealed mild short-term memory deficits, executive functioning impairments, and failures to correctly name common objects. Anomia examples included a failure to name a cup (Mrs. P’s response was “something to drink from”). Behavioral changes included difficulty dressing, inattention to hygiene, impulsiveness, apathy, and missed social cues. Mrs. P lacked insight and expressed no distress with being diagnosed with a cognitive disorder. She was indifferent and occasionally giddy during a discussion of her impairments. Other findings included a lack of spontaneity, unreasonable rigidity in routines, and out-of-context rage when pressed to deviate from established routines. At an interval exam, Mrs. P’s word-finding difficulties were obvious on casual observation, and she would laugh out of context to the setting. Collateral history confirmed disinhibited and unpredictable behaviors. The patient endorsed infrequent depressed moods. Mrs. P denied anhedonia, insomnia, loss of self-esteem, and suicidal ideations. She denied appetite changes but endorsed increased food intake, mostly impulsive hyperphagia focused on sweets. Follow-up exams evidenced stereotyped behaviors in motor and speech patterns. She lacked awareness of continuous hand-rubbing, rocking back and forth, and repeating words and phrases not directed at meaningful communication. Mrs. P acknowledged difficulty with following plots in novels she had tried to read and television programs she had recently watched, without any accompanying distress.
Both computed tomography and magnetic resonance imaging scans of the brain revealed cortical atrophy inconsistent with the patient’s chronological age, along with evidence of frontotemporal lobar atrophy. Serology testing for syphilis was non-reactive. Thyroid-stimulating hormone and thyroxine levels were within reference limits. Complete blood count and a complete metabolic panel were unremarkable. Folate and vitamin B12 levels revealed no deficiencies suggestive of malabsorption. A urine drug screen and routine urinalysis were negative for any abnormal findings. Mrs. P was diagnosed with FTLD, based on an early, gradual, and progressive decline in behavior and language. These changes were coupled with a loss of executive functioning and abnormal findings supportive of FTLD on neuroimaging. Frontal lobe abnormalities were further localized from neuropsychological testing.
The authors report no relevant financial relationships.
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