Frontotemporal Dementia in an Elderly Patient: A Diagnostic Enigma

Frontotemporal dementia (FTD) is the second most common form of dementias under the age of 65 and the third most common cause of primary degenerative dementias after Alzheimer’s disease and Lewy body dementia. It typically begins between the ages of 45 and 65 and is seen equally in both genders. The onset of the disease is insidious, and its defining features include profound alterations in personality and behavior along with speech and language impairment. Other features of the disease include perseverative and compulsive behavior, hyperorality, decline in social cognition and executive abilities, and changes in eating patterns.^1-5 

The frontal and temporal lobes of the brain play a critical role in emotion, social functioning, dietary behavior, and causation of stereotyped and compulsive behaviors. This explains why we see such symptoms in people with pathological changes in those areas of the brain.⁵ Published information about specific risk factors for FTD is limited. Recognized risk factors include family history—seen in about 50% of diagnosed cases—and a history of head trauma.^2,6 

Despite being a significant cause of dementia, FTD is often misdiagnosed and not recognized. The current criteria that have been established for diagnosing FTD—formally known as the consensus criteria—as well as The Diagnostic and Statistical Manual of Mental Disorders (5th ed) (DSM-5) criteria describe the core features of FTD. However, it has been found that only about one third of patients diagnosed with FTD have all these core features on initial presentation.³ This creates a challenge for physicians to accurately diagnose FTD, especially on its initial presentation. In this case study, we report a female patient with no past psychiatric history, who presented with profound changes in her behavior and personality, along with apparent mild cognitive impairment.

Case Report

The patient is a 68-year-old woman from a nursing home (NH) who presented to the emergency room (ER) with a history of unspecified dementia, diagnosed in January 2016. 

Prior to her first admission in early 2016, the patient was apprehended by the police after she had stolen beer from a liquor store. She had no history of any such behavior. The patient was discharged to a NH in March 2016; there, she attempted to elope several times and persistently demanded to return to her own apartment. 

During the index admission, we noted the patient to be unkempt, restless, agitated, and extremely intrusive. She followed the treatment team around the unit despite multiple attempts at redirection. The patient was alert and oriented to date but displayed some memory impairment, more so with her long-term memory. The patient was unable to plan a simple menu for her meals. Her mood was euphoric, and she frequently said, “I love you” to staff members. Her impulse control, insight, and judgment were poor; she was extremely preoccupied with getting discharged to her apartment and paying her rent. She was facing eviction due to missed rent payments for the past 5 months.

Upon hospital admission following the ER visit, we found the patient was a poor historian and did not have any living family members. She appeared to have difficulty making sentences; she was substituting words and had a significantly impaired ability to name objects. Collateral information, from her friend, revealed that she was a high-functioning individual who attended an Ivy League institution and then went onto study and teach cultural anthropology. There was no past psychiatric history, head trauma, or illicit drug or alcohol abuse. There was no family history of mental illness. Her past medical history was only significant for hypertension. 

Laboratory tests, including complete blood count, complete metabolic profile, thyroid-stimulating hormone level, vitamin B12 and folate levels, serum rapid plasma reagin, and electrocardiogram, were within normal limits. The patient underwent magnetic resonance imaging (MRI), which revealed differential anterior temporal lobe and hippocampal atrophy, age-appropriate generalized atrophy of lesser magnitude, and ischemic white matter disease. (Figure 1) The patient’s presentation prompted neuropsychological testing. Her Mini-Mental State Examination score was 23 out of 30. 

On the Wechsler’s Adult Intelligence Scale Fourth Edition (WAIS-IV),⁷ her full-scale IQ of 66 was at the first percentile. The results of her WAIS-IV revealed severe impairment in multiple domains of cognitive functioning. Her verbal comprehension, working memory, and processing speed were all in the significant below-average range. However, she displayed relatively preserved perceptual reasoning skills, which were found to be an area of personal strength and in the average range of intellectual functioning. 

The results of the Dementia Rating Scale (DRS-2)⁸ also indicated significant impairment across several areas of functioning consistent with a diagnosis of dementia. Her initiation and preservation abilities were severely impaired; her conceptualization was moderately impaired; her attention was mildly impaired; and her construction ability was below average. Her overall cognitive functioning, as measured by the DRS-2 Total Score, was 91 out of a possible 133 points, which corresponds to an age- and education- corrected scaled score of 0 (< 1st percentile range) and indicates a severely impaired level of performance.

Her scores on the individual subtests of the DRS-2 indicated that her most significant impairment was in her memory (< 1st percentile range) and the verbal skills areas (< 1st percentile range).

On the Boston Naming Test,⁹ she was able to recall only 1 out of 60 line drawings shown. This fell into severe impairment range (< 1st percentile range) indicating severe aphasia. This provided further evidence along with her scores on the DRS-2 and the WAIS-IV that she had severe impairment in the frontal and temporal lobes consistent with an FTD.  

She required 107 seconds to complete part A of Trail Making Test¹⁰ and 214 seconds to complete part B. These scores (< 10th percentile range) indicated deficient processing speed and executive functioning.

Her Controlled Oral Word Association Test¹¹ score was 4, indicating she was able to generate four words beginning with the appropriate letters (< 10th percentile) and her total Animal Naming task¹² score was 1 (<10th percentile), indicating she generated one animal name during the 60-second time period allotted. These scores suggest severe impairment in her verbal fluency ability.

On the Rey Complex Figure Test,¹³ she was able to copy the figure but was unable to reproduce it from memory. Additionally, she was unable to recall any part of the figure when prompted by the examiner. These results indicated some preservation in her constructive skills but significant impairment in her reconstructive abilities when required to reproduce the figure from memory. These results are consistent with her DRS-2 and WAIS-IV tests. On the clock-drawing test,¹⁴ she drew the numbers one through 20 around the clock and was unable to draw the time ten minutes to seven. 

During her hospital course, the patient continued to be intrusive and preoccupied with discharge to her apartment. She was started on memantine 5 mg by mouth daily, risperidone 0.5 mg by mouth daily and titrated to twice a day, and valporic acid 250 mg by mouth daily, titrated to three times a day. The patient’s intrusive behavior and agitation improved, however her preoccupation about going home persisted.

Discussion

FTD accounts for up to 20% of patients with pre-senile dementia and 10% of all patients with dementing disease, making it a significant cause of dementia.^2,3 Yet, it continues to be poorly recognized by physicians. What makes FTD unique is its heterogeneity of clinical presentation. Some patients present with disinhibited, socially inappropriate behavior and fatuous, purposeless overactivity, while others present as apathetic, inert, mentally rigid, and perseverative.⁵ These differences may be due to the area of the brain affected most. Patients with predominately disinhibited behavior may have pathological changes to the orbitomedial frontal and anterior temporal regions, while those with stereotypic and perseverative behavior have marked striatal changes and an emphasis on the temporal lobes.⁵

FTD can be divided into three major subgroups: (1) behavioral variant, (2) semantic dementia, and (3) progressive nonfluent dementia. In the behavioral variant of FTD, behavioral, personality, and executive functioning impairments are the primary symptoms and, on brain imaging, frontal lobe atrophy is often predominent.² Semantic dementia typically starts with a language abnormality in which the patient has difficulty recalling words and their meaning. This variant is most often accompanied by atrophy in the middle and anterior temporal lobes.¹⁵ Lastly, progressive nonfluent aphasia is characterized by non-fluent speech attributed to apraxia of speech and limited mental search for words. This subtype is associated with atrophy that is greater in the left inferior frontal lobe, specifically Brocas area.^16,17

Although FTD has been subdivided into three separate syndromes, it is difficult to make a clear-cut distinction between them. This is due to overlapping symptoms among the three syndromes. It has been found that, more often than not, there is a co-occurrence of behavioral and language impairments across all types of frontotemporal degeneration.¹⁸ This, again, complicates the accurate diagnosing of FTD. In addition, in FTD, behavior, speech, and mood symptoms are typically seen before symptoms of memory impairment. These clinically heterogeneous symptoms, may lead to a misdiagnosis, especially of psychiatric disorders such as depression, bipolar disorder, obsessive-compulsive disorder, or schizophrenia, which can present with certain features seen in FTD as well.^19,20 Other differential diagnoses may include progressive supranuclear palsy, which has a similar behavioral and neuropsychological profile.¹⁹ Table 1 provides additional common differential diagnoses of FTD. 

As a whole, our patient’s neurocognitive evaluation showed an individual with significant impairment across multiple cognitive domains, often found among patients with dementia. The areas with significant impairment included working memory, long-term memory, and verbal fluency. She also displayed significant agnosia and deficits in executive functioning and processing speed. She exhibited a relatively preserved ability to copy complex figures but had an impaired ability to perceptually organize both verbal and visual information when having to reproduce or generate information from memory. Such impairments in the areas of working memory, agnosia, executive functioning, and perceptual organization are frequently linked to degradation in the frontal and temporal lobes.^2,3 This pattern of deterioration was consistent with her MRI, which showed differential atrophy of the anterior temporal lobe and hippocampus, left greater than right, with age-appropriate ischemic white matter disease and generalized atrophy of lesser magnitude.

Upon our initial encounter with this patient, it appeared that her relatively mild cognitive impairment, from a clinical perspective, was disproportionate to her profound behavioral and personality changes; this prompted us to do further investigation. The findings of the MRI and neuropsychological testing facilitated the diagnosis of FTD. Her clinical picture supported the DSM-5 criteria for probable frontotemporal neurocognitive disorder, which includes an insidious onset and gradual progression of behavioral disinhibition, lack of insight, perseverative, compulsive behaviors, decline in social cognition and executive abilities, prominent decline in language abilities with relative sparing of memory and perceptual motor function, and no evidence of other etiological conditions.

Along with the above clinical symptoms, FTD also presents with progressive degeneration of the frontal lobes, anterior temporal lobes, or both as seen on imaging. In our case, structural imaging using MRI was done, which has been found to be more sensitive than computed tomography.⁵ The importance of neuropsychological testing is also crucial in the evaluation of a patient with possible FTD. Neuropsychiatric changes are the most prominent symptoms, and they may often appear well before or overshadow cognitive impairments. On these neuropsychological tests, an early impairment of executive functioning is often seen.³

Conclusion

FTD should be considered in all patients who present with insidious changes in personality and behavior accompanied by lack of insight and speech and language impairments. In such cases, it is important to obtain a full history, neuropsychological testing, and structural brain imaging in order to distinguish between FTD and other neurocognitive and psychiatric disorders. 

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