Abstract
Diagnosis of frontotemporal dementia is challenging in the early stages. Various psychiatric and neurological diseases are misdiagnosed as frontotemporal dementia and vice versa. Here we present a case with right temporal variant of frontotemporal dementia who presented with alcohol dependency and remarkable behavioral symptoms and was first misdiagnosed as having alcohol-related dementia. He then revealed symptoms related to right temporal variant of frontotemporal dementia, such as prosopagnosia, difficulty recognizing his housemates, loss of empathy, ritualistic behaviors, and difficulty finding and comprehending words. Retrospectively, his alcohol dependency itself was considered an early manifestation of right temporal variant of frontotemporal dementia.
Keywords
INTRODUCTION
Clinical diagnosis of frontotemporal dementia or behavioral variant frontotemporal dementia is challenging, particularly in the early stages [1]. Psychiatric and neurological diseases, including other types of dementia, are often misdiagnosed as frontotemporal dementia [2–4], and, according to one study, an initial diagnosis of frontotemporal dementia is changed after follow-up in almost half of all cases, which was mostly reclassified with a psychiatric diagnosis [5]. Conversely, approximately 50% of patients with behavioral variant frontotemporal dementia receive a prior psychiatric diagnosis [6]. According to Ducharme et al. (2020), average diagnostic delay is up to 5–6 years from symptom onset mainly because of difficulty differentiating between frontotemporal dementia and psychiatric disorders [6]. Thus, despite significant efforts to establish clinical guidelines that allow for a differential diagnosis, the diagnostic accuracy for frontotemporal dementia is still not satisfactory [6, 7]. This is especially true for right temporal variant of frontotemporal dementia, which has no separate diagnostic criteria yet due to its relatively equivocal symptoms [8].
Further confusing the diagnosis, alcohol consumption has been proposed to increase in patients during the initial stages of frontotemporal dementia because of changes in their pursuit of rewards [9–11]. Indeed, alcohol use disorder has been described in a case report of frontotemporal dementia [12]. Alcohol use disorder sometimes leads to so-called alcohol-related dementia [13], which includes behavioral symptoms as one of its symptoms [13], a hallmark of frontotemporal dementia [1]. Thus, it is not surprising that clinicians might misdiagnose frontotemporal dementia as alcohol-related dementia. Here we present a case with right temporal variant of frontotemporal dementia who was first misdiagnosed as having alcohol-related dementia. Afterwards, he revealed typical symptoms associated with behavioral variant frontotemporal dementia such as loss of empathy, ritualistic behaviors, and impairment of contextual social cognition [14–16], as well as those associated with semantic dementia (prosopagnosia, difficulty recognizing housemates, and difficulty finding and comprehending words). He was finally diagnosed as having right temporal variant of frontotemporal dementia 8 years post-onset.
CASE PRESENTATION
This study was performed after obtaining informed consent from the patient and his family member.
Alcohol dependency and its associated alcoholic cardiomyopathy
The patient was a right-handed man with 12 years of education and was a hard-working person. He and his family members had no history of neurological or psychiatric disorders. For the following personal details, his wife and his old sister were the informants. He had been a timber dealer in his family-run business and used to drink socially only a few times each month until he was 60 years old, at which point he began to not pay attention to what others said and became a heavy drinker. There were neither lifestyle changes nor medical conditions that precipitated his behavioral changes. Years of heavy drinking resulted in probable alcoholic cardiomyopathy as well as associated heart failure, which was characterized by dilation and impaired contraction of both myocardial ventricles [17], and he was admitted into the cardiovascular unit in our hospital at age 63. During his stay in the hospital, however, he often broke the rules of the facility, including smoking in his hospital room, stopping his intravenous drip without permission, and overeating and overdrinking despite heart failure treatment that involved a reduction in fluid intake. He was thus forced to be discharged from our hospital before full recovery. After being discharged from the hospital, he still showed a strong desire to take alcohol and had continued to drink a large amount of alcohol (> 60 g/day, the amount of which was defined as a heavy drinker for men [18]) from morning to night for almost 4 years, and was unable to control his alcohol dependence, despite repeated warnings from his doctor and his family members. Regarding alcohol withdrawal syndrome, he never showed any episodes. At age 64, his heart failure worsened after a remarkable increase in alcohol consumption over a period of several weeks, and he was again admitted into the cardiovascular unit in our hospital due to heart failure. He was diagnosed as having alcohol dependence according to International Classification of Diseases 10 (ICD-10) criteria by two board-certified specialists for psychiatry who had > 10 years of experience in psychiatry at the time (MF and TT). While in the unit, he did not present with any signs of alcohol withdrawal syndrome such as tremors, sweating, anxiety, seizures, hallucinations, or impaired consciousness. Likewise, he showed no signs of Wernicke encephalopathy, e.g., ophthalmoplegia, nystagmus, ataxia, or mental confusion, which results from vitamin B-1 deficiency mainly due to alcohol dependence. Indeed, no remarkable findings were evident upon his neurological examination.
Abnormal behaviors
He did, however, have a considerable number of behavioral problems, including excessive consumption of soft drinks despite a prescribed reduction in fluid intake, removing his intravenous drip without permission, and frequently barging into other people’s rooms and sometimes taking food items from their refrigerators. He was then transferred to our neuropsychiatric unit for continued medical treatment. In the neuropsychiatric unit, he again barged into other people’s rooms, talked with patients in their rooms, took some food items from their refrigerators, and ate or drank them without permission. He would keep newspapers and magazines in his possession that had been placed in the dayroom for all patients in the unit to use and would draw graffiti on them.
Cognitive function
Upon neuropsychological assessment, his score on the Japanese version of the Mini-Mental State Examination was 21/30 (incorrect answers were related to subscales of orientation and recall), slightly below the passing cut-off point of 23 for dementia [19]. Verbal and performance intelligence quotients were 77 and 69 on the Japanese version of the Wechsler Adult Intelligence Scale—Third Edition [20], both of which were approximately at the lower limit of normal quotients of 70 to 130. The subtest scores were verbal comprehension index 76, perceptual organization index 68, working memory index 94, and processing speed index 84, respectively. The Japanese version of the Rivermead Behavioural Memory Test [21] was used to assess episodic memory function, in which he scored 4 out of a maximum of 12 points, slightly below the cut-off point of 5, with both visual and verbal memory functions being equally impaired. Regarding executive function, his score on the Japanese version of the Behavioral Assessment of the Dysexecutive Syndrome [22] was 63, which was below the lower limit of the normal score of 70. Taken together, his neuropsychological assessment indicated that his intelligence, episodic memory, and executive functions had deteriorated, the results of which were consistent with those of alcohol-related dementia [13]. Computed tomography of his head showed an atrophy in the right anterior temporal pole (Fig. 1), which was not considered as important at that time. During his stay in our hospital, his wife divorced him because of his abnormal behaviors, and he entered a nursing home.
Computed tomography of the patient’s head at age 64. A slight atrophy in the right anterior temporal pole is indicated (arrow).
Symptoms related to frontotemporal dementia
After he entered the nursing home, his old sister and his primary caregiver in the nursing home provided the following personal details. He was forced to stop drinking alcohol and never drank alcohol in the nursing home. His heart failure improved to the point where the amount of his diuretics could be substantially reduced and then he never showed an episode of acute heart failure again, indicating that his heart failure had been a result of alcoholic cardiomyopathy, whose diagnosis relies on the improvement in cardiac function after abstinence from alcohol [17].
Abnormal behaviors and semantic memory deficits
After being discharged, he visited the cognitive function clinic affiliated with our hospital once every few months, where he spoke at length about the same topic concerning his desire to live longer without listening to what a doctor had to say, and he would leave the consultation room immediately after a doctor talked to him. These behaviors suggested that he had lost the ability to understand and share the thoughts or feelings of another, namely, loss of empathy. At this time, he showed obvious semantic memory deficits in his daily living. He began to take eggplants from the garden in the nursing home and to eat raw eggplants immediately without cooking them, which never happens in Japan. At age 68, he could no longer recognize his housemates and his graffiti of people’s faces became strange with green hair and blue faces, all of which reflected semantic memory impairment. He also showed a stereotyped schedule in which he would come to the dining room at exactly 7:30, brush his teeth at 8:00 punctually, and go to the daycare center at exactly 9:00. He tried to live on this fixed schedule no matter what day it was, although the daycare center was closed on Sundays. Regarding behavioral symptoms, he continued to barge into other people’s rooms in the nursing home, took books or magazines from their rooms, and cut out photos from those books or magazines. Thus, the patient’s abnormal behaviors continued and worsened, suggesting that his abnormal behaviors were not caused by alcohol-related dementia, at least those revealed after he entered the nursing home, because, for patients with alcohol-related dementia who has been abstinent from alcohol for more than a year, the cognitive impairment is non-progressive or even partially reversible [23].
Cognitive function
No remarkable findings were evident upon his neurological examination. Upon neuropsychological examination at age 66, the scores on his general cognitive function and intelligence assessments remained at mild impairment or around the lower limits of normal values: his score on the Japanese version of the Mini-Mental State Examination [19] was 20/30 (the passing cut-off point is 23), and his verbal and performance intelligence quotients were 71 and 80 (normal quotients, 70 to 130) on the Japanese version of the Wechsler Adult Intelligence Scale—Third Edition [20]. The subtest scores were verbal comprehension index 71, perceptual organization index 87, working memory index 88, and processing speed index 94, respectively. Notably, his verbal comprehension index and working memory index went down from 77 to 71 and from 94 to 88, indicating that his linguistic function might have deteriorated. On the contrary, his perceptual organization index and processing speed index went up from 69 to 87 and from 84 to 94, respectively, which is considered to be resulted from improvement in visuospatial function and attentional function after abstinence [24]. In contrast, his score of the picture version of the pyramid and palm trees test [25], a semantic memory examination, was extremely poor with a score of 21/52 (45.2±2.6 for healthy Japanese controls [26]) at age 67. Similarly, he scored 0 out of 16 in the famous people naming task in Visual Perception Test for Agnosia (15.2±2.0 for healthy Japanese controls) [27], reflecting his extremely severe prosopagnosia. His semantic memory deficits eventually affected linguistic function; he gradually exhibited difficulty finding and comprehending words and also showed surface dyslexia at age 68. He was finally diagnosed as having right temporal variant of frontotemporal dementia, in which characteristic symptoms for both behavioral variant frontotemporal dementia (loss of empathy, abnormal behaviors, ritualistic behaviors, and impairment of contextual social cognition [14–16]) and semantic dementia (prosopagnosia, difficulty recognizing his housemates, word-finding difficulties, and single word comprehension deficits) were present [8, 29]. Retrospectively, he had suffered from right anterior temporal variant of frontotemporal dementia since he was 60 and his alcohol dependency itself is considered to be an early manifestation of frontotemporal dementia [9–11]. His T1-weighted magnetic resonance imaging of the head at age 69 (Fig. 2A) revealed atrophy in the bilateral anterior temporal lobes. Relative hypoperfusion was evident in the same area by 99 mTc-ethyl cysteinate dimer (Tc-99 m ECD) single-photon emission computed tomography (SPECT), the results of which were analyzed with an easy Z-score imaging system [30] (Fig. 2B).
A) Magnetic resonance imaging of the patient’s head at age 69. A remarkable atrophy is found in the bilateral anterior temporal poles (arrows). B) Area of relative hypoperfusion (Z score > 2) in the patient’s brain at age 69 as demonstrated by a Z-score imaging system with Tc-99m ECD SPECT. From left to right, the brain images indicate the right, left, inferior, and anterior views. Red represents the most severe hypoperfusion (Z score > 5), whereas black represents moderate hypoperfusion (Z score > 2). Prominent hypoperfusion was noted in the bilateral anterior temporal poles.
DISCUSSION
We describe here an individual with right temporal variant of frontotemporal dementia who was first misdiagnosed as having alcohol-related dementia and was finally diagnosed correctly 8 years post-onset. Although impairments in visuospatial function, attention, and episodic memory observed at the initial neuropsychological examination as well as part of behavioral symptoms are considered to be caused by alcohol use disorder [24], most of symptoms in the initial stages and advanced stages, e.g., hyperorality, loss of empathy, prosopagnosia, difficulty recognizing housemates, and most of behavioral symptoms including compulsiveness, are compatible with those of the right temporal variant of frontotemporal dementia [8, 16]. In contrast, these symptoms are not the characteristics of alcohol-related dementia. Rather, the hallmark of alcohol-related dementia is cognitive impairment in executive function, visuospatial function, episodic memory, working memory, and attention as well as postural instability, which continue to be observed even after long-term abstinence [23, 31] and are related to brain areas of frontal-striatal circuit, hypothalamus, and cerebellum [13, 32], but not the temporal pole. He is now considered to have already had the right temporal variant of frontotemporal dementia at the time of his initial misdiagnosis. Retrospectively, his alcohol dependency was one of the initial signs of this type of frontotemporal dementia. We should have placed more importance on his initial symptoms and neuropsychological findings. For example, hyperorality (excessive consumption of soft drinks in this case) is not a typical sign of alcohol-related dementia [13], which might have helped suspect the diagnosis of frontotemporal dementia at the initial stages. In terms of neuroanatomy, the atrophy in his right temporal pole that was demonstrated in the initial imaging should have been taken more seriously. Although this is not the case with this patient, taking a family medical history might help differentiate between frontotemporal dementia and alcohol-related dementia because a strong family history for dementia has been found in patients with right temporal variant of frontotemporal dementia [33].
Although several cognitive dysfunctions of this patient, e.g., executive dysfunction, social cognition deficits, or behavioral symptoms, may be partly related to his behavioral changes, disturbance in the reward system most likely played a key role in developing his alcohol dependency. According to Perry [10], alcohol consumption increases during the initial stages of frontotemporal dementia along with a preference for sweet foods. This is explained by changes in the individuals as the disease progresses in their pursuit of rewards, which include alcohol, food, money, and sex. Insensitivity to negative information is thought to be a key component of the reward-seeking behaviors in frontotemporal dementia and may be related to the degeneration of regions that are involved in emotional representation [11], which include the right anterior temporal pole [28]. In fact, altered food preference and excessive alcohol consumption are more prevalent in patient with right temporal variant of frontotemporal dementia when compared with those of left temporal variant [8, 34]. Another potential background behind the altered food preference in this case is semantic memory impairment for taste, which is related to the temporal lobe [35–37]. This might explain the difference of the dietary changes between semantic dementia and behavior variant of frontotemporal dementia [38] or between right temporal variant of frontotemporal dementia and behavior variant of frontotemporal dementia [8]. Thus, it is probable that some patients with right anterior temporal atrophy present with alcohol dependency and/or alcohol-related dementia. Diagnose of alcohol-related dementia should be applied after all other possible diagnoses have been ruled out because there are various confounding factors, such as concomitant use disorder of other substances; associated complications, such as head injury and psychiatric comorbidities; and a higher rate of vascular risk factors, all of which may independently predispose an individual to cognitive decline [23].
In conclusion, alcohol dependency and/or alcohol-related dementia might be an early manifestation of right temporal variant of frontotemporal dementia in some cases, and clinicians should thus consider a patient’s medical history, a family medical history, symptoms, and imaging findings carefully.
