Symptoms Of Frontotemporal Lobar Degeneration Research Articles

Sensitivity of the Social Behavior Observer Checklist to Early Symptoms of Patients With Frontotemporal Dementia.

Changes in social behavior are common symptoms of frontotemporal lobar degeneration (FTLD) and Alzheimer disease syndromes. For early identification of individual patients and differential diagnosis, sensitive clinical measures are required that are able to assess patterns of behaviors and detect syndromic differences in both asymptomatic and symptomatic stages. We investigated whether the examiner-based Social Behavior Observer Checklist (SBOCL) is sensitive to early behavior changes and reflects disease severity within and between neurodegenerative syndromes. Asymptomatic individuals and patients with neurodegenerative disease were selected from the multisite ALLFTD cohort study. In a sample of participants with at least 1 time point of SBOCL data, we investigated whether the Disorganized, Reactive, and Insensitive subscales of the SBOCL change as a function of disease stage within and between these syndromes. In a longitudinal subsample with both SBOCL and neuroimaging data, we examined whether change over time on each subscale corresponds to progressive gray matter atrophy. A total of 1,082 FTLD pathogenic variant carriers and noncarriers were enrolled (282 asymptomatic, 341 behavioral variant frontotemporal dementia, 114 semantic and 95 nonfluent variant primary progressive aphasia, 137 progressive supranuclear palsy, and 113 Alzheimer disease syndrome). The Disorganized score increased between asymptomatic to very mild (p = 0.016, estimate = -1.10, 95% CI = -1.99 to -0.22), very mild to mild (p = 0.013, estimate = -1.17, 95% CI = -2.08 to -0.26), and mild to moderate/severe (p < 0.001, estimate = -2.00, 95% CI = -2.55 to -1.45) disease stages in behavioral variant frontotemporal dementia regardless of pathogenic variant status. Asymptomatic GRN pathogenic gene variant carriers showed more reactive behaviors (preoccupation with time: p = 0.001, estimate = 1.11, 95% CI = 1.06 to 1.16; self-consciousness: p = 0.003, estimate = 1.77, 95% CI = 1.52 to 2.01) than asymptomatic noncarriers (estimate = 1.01, 95% CI = 0.98 to 1.03; estimate = 1.31, 95% CI = 1.20 to 1.41). The Insensitive score increased to a clinically abnormal level in advanced stages of behavioral variant frontotemporal dementia (p = 0.003, estimate = -0.73, 95% CI = -1.18 to -0.29). Higher scores on each subscale corresponded with higher caregiver burden (p < 0.001). Greater change over time corresponded to greater fronto-subcortical atrophy in the semantic-appraisal and fronto-parietal intrinsically connected networks. The SBOCL is sensitive to early symptoms and reflects disease severity, with some evidence for progression across asymptomatic and symptomatic stages of FTLD syndromes; thus, it may hold promise for early measurement and monitoring of behavioral symptoms in clinical practice and treatment trials. This study provides Class II evidence that the SBOCL is sensitive to early behavioral changes in FTLD pathogenic variants and early symptomatic individuals in a highly educated patient cohort.

[Coping and Supporting Patients and Families of Frontotemporal Lobar Degeneration].

Frontotemporal lobar degeneration (FTLD) is a comprehensive term encompassing a group of clinically overlapping but heterogeneous conditions with selective frontal and temporal lobar neurodegeneration. Among the three clinical subtypes of FTLD, behavioral variant frontotemporal dementia (bvFTD) and semantic dementia (SD) were specified as "designated intractable diseases" by the Japanese Ministry of Health, Labor and Welfare in 2015. Under this designation system, relatively young patient with bvFTD or SD of certain severities can receive partial financial support from the Japanese local government. Here we introduce financial and social support for FTLD, including utilization of the designated intractable disease system and other support available in Japan. In addition, we describe the methods for coping and care of prominent symptoms in FTLD. Lastly, we address the current status of a nationwide Japanese FTLD study cohort named FTLD-J.

Effect of Functional BDNF and COMT Polymorphisms on Symptoms and Regional Brain Volume in Frontotemporal Dementia and Corticobasal Syndrome.

The authors examined the effects of two common functional polymorphisms-brain-derived neurotrophic factor (BDNF) Val66Met and catechol-O-methyltransferase (COMT) Val158Met-on cognitive, neuropsychiatric, and motor symptoms and MRI findings in persons with frontotemporal lobar degeneration (FTLD) syndromes. The BDNF Val66Met and COMT Val158Met polymorphisms were genotyped in 174 participants with FTLD syndromes, including behavioral variant frontotemporal dementia, primary progressive aphasia, and corticobasal syndrome. Gray matter volumes and scores on the Delis-Kaplan Executive Function System, Mattis Dementia Rating Scale, Wechsler Memory Scale, and Neuropsychiatric Inventory were compared between allele groups. The BDNF Met allele at position 66 was associated with a decrease in depressive symptoms (F=9.50, df=1, 136, p=0.002). The COMT Val allele at position 158 was associated with impairment of executive function (F=6.14, df=1, 76, p=0.015) and decreased bilateral volume of the head of the caudate in patients with FTLD (uncorrected voxel-level threshold of p<0.001). Neither polymorphism had a significant effect on motor function. These findings suggest that common functional polymorphisms likely contribute to the phenotypic variability seen in patients with FTLD syndromes. This is the first study to implicate BDNF polymorphisms in depressive symptoms in FTLD. These results also support an association between COMT polymorphisms and degeneration patterns and cognition in FTLD.

Translation, cross-cultural adaptation and applicability of the Brazilian version of the Frontotemporal Dementia Rating Scale (FTD-FRS).

BACKGROUNDStaging scales for dementia have been devised for grading Alzheimer's disease (AD) but do not include the specific symptoms of frontotemporal lobar degeneration (FTLD).OBJECTIVETo translate and adapt the Frontotemporal Dementia Rating Scale (FTD-FRS) to Brazilian Portuguese.METHODSThe cross-cultural adaptation process consisted of the following steps: translation, back-translation (prepared by independent translators), discussion with specialists, and development of a final version after minor adjustments. A pilot application was carried out with 12 patients diagnosed with bvFTD and 11 with AD, matched for disease severity (CDR=1.0). The evaluation protocol included: Addenbrooke's Cognitive Examination-Revised (ACE-R), Mini-Mental State Examination (MMSE), Executive Interview (EXIT-25), Neuropsychiatric Inventory (NPI), Frontotemporal Dementia Rating Scale (FTD-FRS) and Clinical Dementia Rating scale (CDR).RESULTSThe Brazilian version of the FTD-FRS seemed appropriate for use in this country. Preliminary results revealed greater levels of disability in bvFTD than in AD patients (bvFTD: 25% mild, 50% moderate and 25% severe; AD: 36.36% mild, 63.64% moderate). It appears that the CDR underrates disease severity in bvFTD since a relevant proportion of patients rated as having mild dementia (CDR=1.0) in fact had moderate or severe levels of disability according to the FTD-FRS.CONCLUSIONThe Brazilian version of the FTD-FRS seems suitable to aid staging and determining disease progression.

Pharmacological treatment of frontotemporal lobar degeneration: systematic review

To identify the therapeutic options available for treatment of cognitive and behavioral symptoms in frontotemporal lobar degeneration. Systematic review using the descriptors "frontotemporal lobar degeneration" OR "frontotemporal dementia" OR "fronto-temporal dementia" OR "fronto-temporal degeneration" OR "Pick's disease" OR "Pick's atrophy" OR "semantic dementia" OR "progressive aphasia" AND "pharmacotherapy" OR "treatment" OR "efficacy" OR "effects" OR "management" was performed in the Medline and Lilacs databases. Quality A - randomized clinical trials. Quality B - open studies or reports of six or more cases. Quality C - reports of five or fewer cases. Two reviewers independently assessed the clinical studies. Information collected included diagnostic criteria used, sample size, duration, efficacy and tolerability measures used and results obtained. From the 532 studies found, 29 complied with the inclusion criteria. All studies worked with a small sample, had short duration of treatment and used non-uniform measures in evaluating efficacy and tolerability. Studies showed disparate results with respect to behavior and cognition. There is still little, and poor, evidence available for treatment of frontotemporal lobar degeneration and studies with better methodological background are needed.

Effect of ferulic acid and Angelica archangelica extract on behavioral and psychological symptoms of dementia in frontotemporal lobar degeneration and dementia with Lewy bodies

The behavioral and psychological symptoms of dementia place a heavy burden on caregivers. Antipsychotic drugs, though used to reduce the symptoms, frequently decrease patients' activities of daily living and reduce their quality of life. Recently, it was suggested that ferulic acid is an effective treatment for behavioral and psychological symptoms. We have also reported several patients with dementia with Lewy bodies showing good responses to ferulic acid and Angelica archangelica extract (Feru-guard). The present study investigated the efficacy of Feru-guard in the treatment of behavioral and psychological symptoms in frontotemporal lobar degeneration and dementia with Lewy bodies. We designed a prospective, open-label trial of daily Feru-guard (3.0 g/day) lasting 4 weeks in 20 patients with frontotemporal lobar degeneration or dementia with Lewy bodies. Behavioral and psychological symptoms of dementia were assessed at baseline and 4 weeks after the start of treatment, using the Neuropsychiatric Inventory. The Neuropsychiatric Inventory scores were analyzed using the Wilcoxon rank sum test. Treatment with Feru-guard led to decreased scores on the Neuropsychiatric Inventory in 19 of 20 patients and significantly decreased the score overall. The treatment also led to significantly reduced subscale scores on the Neuropsychiatric Inventory ("delusions", "hallucinations", "agitation/aggression", "anxiety", "apathy/indifference", "irritability/lability" and "aberrant behavior"). There were no adverse effects or significant changes in physical findings or laboratory data. Feru-guard may be effective and valuable for treating the behavioral and psychological symptoms of dementia in frontotemporal lobar degeneration and dementia with Lewy bodies.

Effects of prescribed medications on cognition and behavior in frontotemporal lobar degeneration.

A retrospective chart review of 21 patients meeting core clinical criteria for behavioral or aphasic variants of frontotemporal lobar degeneration (FTLD) was conducted. Data recorded included Folstein Mini-Mental State Examination (MMSE) scores, medications prescribed, and subjective reports of behavioral symptoms from each visit. Behaviors were graded on a scale from 1 to 3 and totaled for each visit. Changes in MMSE and behavior scores between visits 1 month and 6 months apart where a new medication was started were analyzed using a paired t test and were compared between medication classes using an unpaired t test. Acetylcholinesterase inhibitors (AChEIs) were associated with a decrease in MMSE scores by 1.6 (P = .02) and an increase in total behavior scores by 1.0 (P = .03). Mean MMSE and behavior scores were statistically more improved by selective serotonin reuptake inhibitors than AChEIs (P = .04). This data suggest a potential worsening of objective measures of cognitive and behavioral symptoms in FTLD with AChEI treatment.

Executive and behavioral deficits share common neural substrates in frontotemporal lobar degeneration — A pilot FDG-PET study

Behavioral and executive dysfunctions are typical symptoms of frontotemporal lobar degeneration, associated with its subtypes frontotemporal and semantic dementia. Although both functions depend on the frontal lobes, no study has yet compared their neural correlates in frontotemporal lobar degeneration. Accordingly, we correlated clinical scores of behavioral and executive deficits with glucose utilization as measured by [18F]fluorodeoxyglucose positron emission tomography in 17 patients with frontotemporal lobar degeneration and 9 age- and sex-matched control subjects. Impairment in executive functions was measured by the Behavioral Assessment of the Dysexecutive Syndrome, a modified Stroop paradigm and/or the Tower of Toronto Test. Behavioral deficits were examined with the Neuropsychiatric Inventory. Executive dysfunction was correlated with diminished glucose utilization in frontomedial and frontolateral cortices. Brain regions included the anterior cingulate and midcingulate gyri, anterior medial frontal cortex, and left frontolateral cortex. Behavioral deficits were associated with mainly frontomedial networks, particularly the anterior medial frontal cortex, gyrus rectus, and area subcallosa. Our pilot study reveals partially overlapping neural correlates of executive and behavioral dysfunction in frontotemporal lobar degeneration. The results suggest that some behavioral deficits, namely disinhibition and appetite and eating abnormalities, are particularly related to executive dysfunction. This hypothesis might be further explored in studies involving larger patient groups.

Neuroanatomy of Apathy and Disinhibition in Frontotemporal Lobar Degeneration

Objective: To investigate the neural basis for the behavioral symptoms of frontotemporal lobar degeneration (FTLD) that cause the greatest caregiver distress. Background: FTLD is a progressive neurodegenerative disease associated with behavioral disturbances. Group studies have related these behaviors to volume loss on MRI. Methods: Forty caregivers of patients with the clinical diagnosis of FTLD completed the Neuropsychiatric Inventory. Twelve neuropsychiatric symptoms and the associated caregiver distress were assessed. Optimized voxel-based morphometry identified significant atrophy in subgroups of FTLD patients with isolated behavioral symptoms corresponding to the most distressing behaviors, and we correlated cortical atrophy directly with these distressing behavioral disorders in an unbiased group analysis. Results: The greatest stressors for caregivers were apathy and disinhibition (p < 0.005 for both contrasts). Partially distinct areas of cortical atrophy were associated with these behaviors in both individual patients with these symptoms and group-wide analyses, including the dorsal anterior cingulate cortex and dorsolateral prefrontal cortex in apathetic patients, and the medial orbital frontal cortex in disinhibited patients. Conclusions: Caregiver stress in families of FTLD patients is due in large part to apathy and disinhibition. The anatomic distribution of cortical loss corresponding to these distressing social behaviors includes partially distinct areas within the frontal lobe.

Difficulties in Detecting Behavioral Symptoms of Frontotemporal Lobar Degeneration Across Cultures

Cross-cultural studies of neurodegenerative disorders are especially important when the disease in question is difficult to diagnose, particularly if symptoms of the illness include behavioral disturbances that may be interpreted differently in different cultures. One such disease is frontotemporal lobar degeneration (FTLD), an early-age-of-onset dementia that disproportionately affects social behavior. We report the demographic and neuropsychologic characteristics of more than 300 patients diagnosed with FTLD in the United States, Greece, and Turkey. We find that patients with the frontal variant of frontotemporal dementia (FTD) are diagnosed at an earlier age and report earlier symptom onset in the United States than in Greece or Turkey. Furthermore, neuropsychologic measures indicate that at diagnosis, FTD patients in the United States are less impaired than patients in Greece and Turkey. Patients with FTD in Greece and Turkey are diagnosed later in the disease, presumably because their behavioral symptoms are not easily detected by the medical system in these countries. Our study underscores the need to create culturally appropriate indices of the behavioral symptoms of FTLD, so that patients may be diagnosed and treated at an earlier stage.

A Case of Frontotemporal Lobar Degeneration (FTLD) With Panic Attack as the First Symptom

Back to table of contents Previous article Next article LETTERFull AccessA Case of Frontotemporal Lobar Degeneration (FTLD) With Panic Attack as the First SymptomShutaro Nakaaki M.D., Ph.D.,Yoshie Murata M.Sc.,Yoshihiro Shinagawa M.D.,Jin Hongo M.D.,Toshi A. Furukawa M.D., Ph.D.,Junko Sato M.Sc.,Hiroshi Tatsumi M.Sc.,Shutaro Nakaaki M.D., Ph.D.Search for more papers by this author,Yoshie Murata M.Sc.Search for more papers by this author,Yoshihiro Shinagawa M.D.Search for more papers by this author,Jin Hongo M.D.Search for more papers by this author,Toshi A. Furukawa M.D., Ph.D.Search for more papers by this author,Junko Sato M.Sc.Search for more papers by this author,Hiroshi Tatsumi M.Sc.Search for more papers by this author,Published Online:1 Oct 2007AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail SIR: It is well known that frontotemporal lobar degeneration (FTLD) is characterized by marked changes in behavior and personality. Although anxiety is identified in 39% of FTLD subjects, agitation ,irritability and depression may also be observed. 1 Compulsive behaviors like OCD symptoms have also frequently been reported as early symptoms. 2 These compulsive behaviors are not associated with overt anxiety that is observed in OCD subjects. However, in the early stages of the FTLD, the symptoms of anxiety may not always distinguish typical anxiety disorder subjects from those suffering from a primary psychiatric disorder. Here, we report a case of FTLD who presented with panic attack as the first symptom. To the best of our knowledge, this is the first case of FTLD manifesting panic attack as the first symptom. Case ReportA 48–year-old married, right-handed woman with 20 years of formal education first experienced a panic attack in April 1997, at the age of 44 years. She had no previous history of psychiatric disease. Her first panic attack occurred when she was going home in the subway from the hospital where her husband’s sister was hospitalized with a diagnosis of lung tumor. The panic attack was characterized by the sudden onset of symptoms such as palpitations, trembling, sensation of shortness of breath, and a feeling of choking, etc., which reached a peak within 10 minutes. During the next 1 month, she suffered from recurrent unexpected panic attacks several times a day in subways or buses, that is, in situations from which escape would have been difficult. In September 1997, she was admitted to the hospital for examination. At admission, she had no abnormal clinical neurological signs. She was therefore diagnosed as a case of panic disorder with agoraphobia. During the next few months, her panic attacks reduced in frequency despite her not having been prescribed any benzodiazepines or other psychotropic medication. In 1998, she gradually started showing diminished interest in her daily activities .In 2001, at the age of 48, her behavior and personality began to show gross changes. She sometimes jogged inappropriately and hugged unfamiliar people, and sang the same TV CM song repeatedly. She began to often exhibit imitation behavior, imitating medical staff’s sign or OK signs repeatedly. In addition, she started showing stereotypic and ritualistic behaviors, such as going to the same restaurant at a certain time. She lost insight into her behavioral and personality changes. MRI showed bilateral frontal lobe atrophy. No other abnormal findings could be detected on MRI. Brain ECD-SPECT showed hypoperfusion in the frontal lobes. Her neuropsychological assessment, including that of memory, language, and attention and executive functions, could not be completed because of both perseverative behavior and lack of interest. However, her episodic and semantic memory and visuospatial ability were relatively well preserved.CommentThis case presented with a panic attack as a symptom of the initial phase of FTLD. Her behavior and personality gradually changed after the appearance of the panic attacks. Her previous medical and psychiatric history were unremarkable. Thus, it is likely that the patient’s first symptom of panic attack at the age of 44 years was a symptom of early stage FTLD. Both substance use and underlying systemic disease were ruled out as the cause of the panic attacks. The patient in the initial phase fulfilled the DSM-IV diagnostic criteria for panic disorder without agoraphobia. The progressive behavioral and personality changes observed in this case, such as loss of insight and decline in social interpersonal conduct, impairments in the regulation of personal conduct, perseveration, stereotypic behavior, and disinhibition, were consistent with the clinical features of FTLD as defined by Neary et al. 3 Both the findings of frontal lobe atrophy on MRI and frontal lobe hypoperfusion on ECD-SPECT supported the diagnosis of FTLD. On the other hand, episodic and semantic memory, perception, and spatial skills were all well preserved. Therefore, the patient was diagnosed as a case of the frontal variant of frontotemporal dementia (fv-FTD). Various behavioral symptoms have been reported as the first symptoms of FTLD. Compulsive behaviors and dietary changes are often observed in the initial stage of FTLD. 2 A recent study indicated that euphoria and aberrant motor activity, and disinhibition are prominent clinical features of FTLD. 4 Thus, to the best of our knowledge, panic attack has never yet been reported as a first symptom in cases of FTLD. A neuroanatomical hypothesis has suggested that panic disorder may result from the dysfunction of a fear network in the brain located in the center of the amygdala. A recent neuroimaging study 5 indicated that subjects with panic disorder have a smaller volume of the amygdala as compared with normal healthy subjects. Even in the early stage of FTLD, not only frontal lobe but also atrophy of the amygdala has been shown by quantitative structural neuroimaging. 6 Therefore, it is likely that dysfunction of the amygdala might be associated with the panic attack in this case. In conclusion, we must carefully observe the course of subjects with panic disorder, especially if the subjects have associated symptoms of apathy, disinbition and stereotypic behaviors. Further study may be expected to lend support to our contention in this case.Department of Psychiatry and Cognitive-Behavioral Medicine, Nagoya City University Graduate School of Medical Sciences, Mizuho-cho, Mizuho-ku, Nagoya, JapanDepartment of Psychiatry and Cognitive-Behavioral Medicine, Nagoya City University Graduate School of Medical Sciences, Mizuho-cho, Mizuho-ku, Nagoya, JapanDepartment of Psychiatry and Cognitive-Behavioral Medicine, Nagoya City University Graduate School of Medical Sciences, Mizuho-cho, Mizuho-ku, Nagoya, JapanDepartment of Psychiatry and Cognitive-Behavioral Medicine, Nagoya City University Graduate School of Medical Sciences, Mizuho-cho, Mizuho-ku, Nagoya, JapanDepartment of Psychiatry and Cognitive-Behavioral Medicine, Nagoya City University Graduate School of Medical Sciences, Mizuho-cho, Mizuho-ku, Nagoya, JapanYagoto HospitalNagoya Daini Red Cross HospitalReferences1 . Porter VR, Buxton WG, Fairbanks LA, et al: Frequency and characteristics of anxiety among patients with Alzheimer’s disease and related dementias. J Neuropsychiatry Clin Neurosci 2003; 15:180–186Google Scholar2 . Mendez MF, Perryman KM, Miller BL, et al: Compulsive behaviors as presenting symptoms of frontotemporal dementia. J Geriatr Psychiatry Neurol 1997; 10:154–157Google Scholar3 . Neary D, Snowden JS, Gustafson L, et al: Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology 1998;51:1546–1554Google Scholar4 . Levy ML, Miller BL, Cummings JL, et al: Alzheimer disease and frontotemporal dementias. behavioral distinctions. Arch Neurol 1996; 53:687–690Google Scholar5 . Massana G, Serra-Grabulosa JM, Salgado-Pineda P, et al: Amygdalar atrophy in panic disorder patients detected by volumetric magnetic resonance imaging. Neuroimage 2003; 19:80–90Google Scholar6 . Boccardi M, Pennanen C, Laakso MP, et al: Amygdaloid atrophy in frontotemporal dementia and Alzheimer’s disease. Neurosci Lett 2002; 25:139–143Google Scholar FiguresReferencesCited byDetailsCited ByJournal of Neurology, Neurosurgery & Psychiatry, Vol. 87, No. 5Primary progressive aphasia beginning with a psychiatric disorderClinics, Vol. 66, No. 8Two Patients with DelusionsPsychiatric Annals, Vol. 40, No. 5Two Patients with DelusionsPsychiatric Annals, Vol. 40, No. 5 Volume 19Issue 4 Fall, 2007Pages 485-487 Metrics PDF download History Published online 1 October 2007 Published in print 1 October 2007

A Model for Management of Behavioral Symptoms in Frontotemporal Lobar Degeneration

Frontotemporal lobar degeneration is a neurologic condition that manifests profound behavioral, personality, and language symptoms. These changes, often unique to each person, may include social misconduct, eating disturbances, apathy, emotional blunting, childlike behavior, habits and rituals, executive dysfunction, and marked difficulty with speech and language. These symptoms occur as the result of cell loss in discrete areas of the brain, the frontal and/or anterior temporal lobes. Little is known about effective management of the behavioral symptoms that result from this disease. The purpose of this paper is to describe a model that could be used in the assessment and potential management of frontotemporal lobar degeneration behavioral symptoms. Suggestions for interventions are given for some of the more common FTD behaviors. The impact of behavioral symptoms on the family caregiver is discussed along with strategies for supportive services and recommendations for future study.