Behavior In Frontotemporal Dementia Research Articles

A neuroanatomical and cognitive model of impaired social behaviour in frontotemporal dementia.

Impaired social cognition is a core deficit in frontotemporal dementia (FTD). It is most commonly associated with the behavioural-variant of FTD, with atrophy of the orbitofrontal and ventromedial prefrontal cortex. Social cognitive changes are also common in semantic dementia, with atrophy centred on the anterior temporal lobes. The impairment of social behaviour in FTD has typically been attributed to damage to the orbitofrontal cortex and/or temporal poles and/or the uncinate fasciculus that connects them. However, the relative contributions of each region are unresolved. In this review, we present a unified neurocognitive model of controlled social behaviour that not only explains the observed impairment of social behaviours in FTD, but also assimilates both consistent and potentially contradictory findings from other patient groups, comparative neurology and normative cognitive neuroscience. We propose that impaired social behaviour results from damage to two cognitively- and anatomically-distinct components. The first component is social-semantic knowledge, a part of the general semantic-conceptual system supported by the anterior temporal lobes bilaterally. The second component is social control, supported by the orbitofrontal cortex, medial frontal cortex and ventrolateral frontal cortex, which interacts with social-semantic knowledge to guide and shape social behaviour.

Frontal allographic agraphia in a patient with behavioral variant frontotemporal dementia

ABSTRACT We report a patient with behavioral variant frontotemporal dementia who developed agraphia, irritability, perseverative and stereotyped behavior, and dietary changes. MRI revealed bilateral frontal convexity atrophy. Neuropsychological examination showed fluent aphasia with perseverative allographic agraphia, mild semantic impairment, and dysexecutive syndrome. Allographic agraphia featured unidirectional conversion from hiragana (cursive form of Japanese phonograms) and kanji (Japanese morphograms) to katakana (square form of Japanese phonograms), as opposed to mutual (bidirectional) conversion between hiragana and katakana in parieto-occipital gyri lesions. Furthermore, all letters of the word were converted and this whole-word conversion may be characteristic of perseverative behavior in frontotemporal dementia.

The severity of behavioural symptoms in FTD is linked to the loss of GABRQ-expressing VENs and pyramidal neurons.

AimsThe loss of von Economo neurons (VENs) and GABA receptor subunit theta (GABRQ) containing neurons is linked to early changes in social–emotional cognition and is seen in frontotemporal dementia (FTD) due to C9orf72 repeat expansion. We investigate the vulnerability of VENs and GABRQ‐expressing neurons in sporadic and genetic forms of FTD with different underlying molecular pathology and their association with the presence and severity of behavioural symptoms.MethodsWe quantified VENs and GABRQ‐immunopositive neurons in the anterior cingulate cortex (ACC) in FTD with underlying TDP43 (FTLD‐TDP) (n = 34), tau (FTLD‐tau) (n = 24) or FUS (FTLD‐FUS) (n = 8) pathology, neurologically healthy controls (n = 12) and Alzheimer's disease (AD) (n = 7). Second, we quantified VENs and the GABRQ‐expressing population in relation to presence of behavioural symptoms in the first years of disease onset.ResultsThe number of VENs and GABRQ‐expressing neurons and the ratio of VENs and GABRQ‐expressing neurons over total Layer 5 neuronal population decreased in FTLD‐TDP and FTLD‐FUS, but not in FTLD‐tau, compared to control and AD. The severity of early behavioural symptoms in all donors correlated with a lower VEN and GABRQ neuronal count.ConclusionWe show that in FTD, a loss of VENs together with GABRQ‐expressing pyramidal neurons is associated with TDP43 and FUS pathology. No significant loss was found in donors with FTLD‐tau pathology; however, this could be due to the specific MAPT mutation studied and small sporadic FTLD‐tau sample size. Overall, we show the GABRQ‐expressing population correlates with behavioural changes and suggest they are key in modulating behaviour in FTD.

The brain correlates of behavioral disturbances in frontotemporal dementia

AbstractBackgroundVarious studies have researched singular or clusters of behaviors in frontotemporal dementia (FTD) correlating them with regional brain atrophy in structural MRI data, or hypometabolism in FDG‐PET images, but a multimodal approach is lacking. We identify the brain correlates of modes of variation (i.e., factors) explaining the variability of behavioral and psychological symptoms (BPSD) in frontotemporal dementia (FTD) using multimodal imaging.MethodImaging and behavioral data from 93 FTD patients acquired at NIH were analyzed. They underwent extended neuropsychological assessment including several scales measuring BPSD (UCLA NPI, FrSBe, and Neurobehavioral rating scale), T1‐weighted MRI, and FDG‐PET imaging. Factor analysis was used on the behavioral data to identify modes of variation of BPSD potentially pointing to few common neurobiological substrates across the FTD sample. The identified modes were then related to intersubject brain variability using a newly developed fusion method run on maps of gray matter volume and FDG metabolism obtained.ResultA factor related to decreased emotional/cognitive interaction (loading scores of apathy, executive dysfunction, withdrawal) correlated with volume and function of the right anterior cingulate and orbito‐frontal cortex. A factor expressing variability on mutacism versus disinhibition/euphoria continuum was associated with dysfunction of the right superior primary motor cortex. A factor related to the presence of hallucinations/delusions/suspiciousness was associated with dysfunction of the right anterior insula.ConclusionBPSD variability in patients with FTD can be explained by 3 major modes of variations, each associated with intersubject brain structure/function variability of the right frontal lobe.

Criminal behavior in frontotemporal dementia and Alzheimer's disease

Seniorenkriminalität ist insgesamt ein seltenes Phänomen. Bei älteren Straftätern hat es die Justiz in hohem Maß mit Ersttätern zu tun, die mehrheitlich männlichen Geschlechts sind. Eine mögliche Ursache von Erstkriminalität im höheren Lebensalter stellen Demenzerkrankungen dar. Es ist jedoch wenig dazu bekannt, wie häufig Demenzerkrankungen tatsächlich Ursache delinquenten Verhaltens im höheren Lebensalter sind. Die Demenzprävalenz in Studien mit forensischen Kohorten älterer Straftäter ist sehr heterogen, was vor allem studienmethodisch begründet ist. Längsschnittlich begehen etwa 50 % aller Patienten mit frontotemporaler Demenz und etwa 10 % aller Patienten mit Alzheimer-Demenz Delikte im Erkrankungsverlauf. Die neurobiologischen Entstehungsmechanismen von Delinquenzverhalten im Rahmen von Demenzen sind unvollständig verstanden. Nach aktuellen Erkenntnissen wird davon ausgegangen, dass Erstdelinquenz im Rahmen von Demenzerkrankungen als Folge von Beeinträchtigungen der sozialen Kognition, Empathiefähigkeit und der Verhaltenskontrolle zu verstehen ist. Bedeutsam sind insbesondere frontale und anteriore temporale Hirnstrukturen. Demenzerkrankungen können zu Beeinträchtigungen der Schuldfähigkeit führen, weshalb forensisch-psychiatrische Sachverständige auch mit Demenzerkranken konfrontiert sind. Hierbei müssen ätiologiespezifische Besonderheiten berücksichtigt werden. Insbesondere Erstdelikte im Rahmen wesensuntypischer Persönlichkeitsänderungen nach dem 50. Lebensjahr sollten an eine neurodegenerative Ätiologie denken lassen. Insbesondere frontotemporale Demenzerkrankungen, wie die behaviorale Variante einer frontotemporalen Demenz (bvFTD), aber auch die semantische Demenz (svPPA), prädisponieren zu delinquentem Verhalten.Diese Arbeit fasst aktuelle Erkenntnisse zu dieser forensisch-psychiatrisch, aber auch klinisch relevanten Thematik zusammen.

Cognition and behaviour in frontotemporal dementia with and without amyotrophic lateral sclerosis

ObjectiveThe precise relationship between frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) is incompletely understood. The association has been described as a continuum, yet data suggest that this may be...

Using a second-person approach to identify disease-specific profiles of social behavior in frontotemporal dementia and Alzheimer's disease

Changes in social behavior are recognized as potential symptoms of behavioral-variant frontotemporal dementia (bvFTD) and semantic dementia (SD), yet objective ways to assess these behaviors in natural social situations are lacking. This study takes a truly social (or second-person) approach and examines changes in real-world social behavior in different dementia syndromes, by analyzing non-scripted social interactions in bvFTD patients (n = 20) and SD patients (n = 20), compared to patients with Alzheimer's disease (AD) (n = 20). Video recordings of 10-min conversations between patients and behavioral neurologists were analyzed for the presence of socially engaging (e.g., nodding, smiling, gesturing) and disengaging behavior (e.g., avoiding eye contact, self-grooming, interrupting). Results demonstrated disease-specific profiles, with bvFTD patients showing less nodding and more looking away than AD, and SD patients showing more gesturing than AD. A principal components analysis revealed the presence of four unobserved components, showing atypical disengaging patterns of behavior. Whole-brain voxel-based morphometry analyses revealed distinct neurobiological bases for each of these components, with the brain regions identified previously associated with behavior selection, abstract mentalization and processing of multi-sensory and socially-relevant information, in mediating socially engaging and disengaging behavior. This study demonstrates the utility of systematic behavioral observation of social interactions in the differential diagnosis of dementia.

Frontal Pole Hypometabolism Linked to Reduced Prosocial Sexual Behaviors in Frontotemporal Dementia and Corticobasal Syndrome.

Changes in sexual behaviors in frontotemporal dementia (FTD) are common and multifaceted, but not well characterized. To characterize changes in sexual behaviors and intimacy in FTD compared to corticobasal syndrome (CBS) and normal controls (NC), and to evaluate the neuroanatomical associations of these changes. Spouses of 30 FTD patients, 20 CBS patients, and 35 NC completed the Sexual Symptoms in Neurological Illness and Injury Questionnaire (SNIQ), which captures changes in sexual interest, inappropriate sexual behaviors, and prosocial sexual behaviors. 25 patients with FTD and 14 patients with CBS also received 18-flouorodeoxyglucose positron-emission topography (18FDG-PET) scans to determine the metabolic changes associated with these symptoms. FTD patients showed a greater increase in inappropriate sexual behaviors than CBS patients [p = 0.009] and NC [p < 0.001] and a greater decrease in prosocial sexual behaviors than CBS patients [p = 0.026] and NC [p < 0.001]. Groups did not differ in change in sexual interest. Among both patient groups, the most common change was decreased prosocial sexual behaviors p < 0.01. Hypometabolism in Brodmann's Area 10 (BA10), within the right frontal pole, correlated with decreased prosocial sexual behaviors [p(FWE-corr) <0.05, k = 44]. No anatomical associations were found with other sexual changes. Decreased prosocial sexual behavior was associated with hypometabolism in BA 10, an area tied to social knowledge and theory of mind, supporting the idea that changes reflect social-cognitive deficits due to frontal dysfunction.

Behavioural and Psychological Symptoms of Dementia: Correlates and Impact on Caregiver Distress

Aims: To evaluate the behavioural and psychological symptoms of dementia (BPSD), to determine their correlation with types and stages of dementia and patient demographics, and to assess the impact on caregiver distress. Methods: This cross-sectional study recruited consecutive dementia patients and caregivers who attended our cognitive clinic. Standard criteria were used to classify types of dementia. BPSD were assessed with the Neuropsychiatric Inventory, and its distress scale was used for caregiver distress. Results: Of a total 107 patients, nearly all (99.1%) had at least one BPSD; 71% had ≥4 symptoms. Most frequent were apathy and agitation, followed by irritability, sleep and appetite disorders, and mood disorders; disinhibition and euphoria were least frequent. BPSD were less prominent with increasing age; males showed more agitation. Apathy and eating disorders were more prevalent in the rural community. BPSD were highest in frontotemporal dementia (FTD), followed by dementia with Lewy bodies (DLB), and least in vascular dementia. Hallucinations were more common in DLB, aberrant motor behaviour in FTD. All domains of BPSD, except for anxiety and euphoria, were more prominent with increasing severity of dementia. Increasing BPSD (except for euphoria) caused higher caregiver distress. Conclusion: BPSD are universally present, bear correlates with dementia type and severity, and cause significant caregiver distress.

Clocks, Behavior, and Cognition

The nerve center responsible for controlling our circadian rhythm is located in a cluster of cells known as the suprachiasmatic nucleus in the hypothalamus. Various physiological functions such as sleep, arousal, blood pressure, body temperature, and hormone secretion are regulated in a 24-hour rhythm by this circuit. Somatic cells of other organs have a peripheral clock gene and by synchronizing the rhythm of the central and peripheral clocks, it is possible to live a healthy life. Due to aging and degenerative disease, circadian rhythm gradually collapses. Factors that can contribute to this include reduced expression of the time gene associated with photo stimulation, a reduction in neurotransmitter levels, and reduced melatonin production. Biological clocks play an important role in our emotions, cognitive function, and behavior. Sleep disorders and metabolic disease related to the circadian rhythm affect metabolic and endocrine activities via the autonomic nervous system and the intestinal bacterial flora. Shift work disorder is associated with insomnia and excessive drowsiness as individuals often work during their sleeping hours. Now time management is placed at the center of our society, and it is important to evaluate the medical risk of engaging in shift work. In frontotemporal dementia (FTD), the stereotypical behaviors may be associated with time. In some patients, multiple timed behaviors occupy a considerable part of the patient's daily life. Stereotypical behaviors in FTD are often considered in contrast to obsessive-compulsive disease (OCD). Studies of OCD have found a close correlation between clinical symptoms, cognitive function, and brain function.

Energy expenditure in frontotemporal dementia: a behavioural and imaging study.

SEE FINGER DOI101093/AWW312 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Abnormal eating behaviour and metabolic parameters including insulin resistance, dyslipidaemia and body mass index are increasingly recognized as important components of neurodegenerative disease and may contribute to survival. It has previously been established that behavioural variant frontotemporal dementia is associated with abnormal eating behaviour characterized by increased sweet preference. In this study, it was hypothesized that behavioural variant frontotemporal dementia might also be associated with altered energy expenditure. A cohort of 19 patients with behavioural variant frontotemporal dementia, 13 with Alzheimer's disease and 16 (age- and sex-matched) healthy control subjects were studied using Actiheart devices (CamNtech) to assess resting and stressed heart rate. Actiheart devices were fitted for 7 days to measure sleeping heart rate, activity levels, and resting, active and total energy expenditure. Using high resolution structural magnetic resonance imaging the neural correlates of increased resting heart rate were investigated including cortical thickness and region of interest analyses. In behavioural variant frontotemporal dementia, resting (P = 0.001), stressed (P = 0.037) and sleeping heart rate (P = 0.038) were increased compared to control subjects, and resting heart rate (P = 0.020) compared to Alzheimer disease patients. Behavioural variant frontotemporal dementia was associated with decreased activity levels compared to controls (P = 0.002) and increased resting energy expenditure (P = 0.045) and total energy expenditure (P = 0.035). Increased resting heart rate correlated with behavioural (Cambridge Behavioural Inventory) and cognitive measures (Addenbrooke's Cognitive Examination). Increased resting heart rate in behavioural variant frontotemporal dementia correlated with atrophy involving the mesial temporal cortex, insula, and amygdala, regions previously suggested to be involved exclusively in social and emotion processing in frontotemporal dementia. These neural correlates overlap the network involved in eating behaviour in frontotemporal dementia, suggesting a complex interaction between eating behaviour, autonomic function and energy homeostasis. As such the present study suggests that increased heart rate and autonomic changes are prevalent in behavioural variant frontotemporal dementia, and are associated with changes in energy expenditure. An understanding of these changes and neural correlates may have potential relevance to disease progression and prognosis.

Uncovering Neuroanatomical Networks Responsible for Abnormal Eating Behavior in Frontotemporal Dementia.

Magnetic resonance imaging (MRI) is a powerful tool that allowsus tonotonlyassessatrophicpatternsassociatedwithdisease but to start to unravel the complex associations between regional tissue loss and specific clinical symptoms. Patterns of atrophy associated with frontotemporal dementia (FTD) and its clinical variants have beenwell described and studies have begun to demonstrate that different behavioral symptoms observed across the FTD spectrum have different anatomical loci.1-6 Changes inone’s eatingbehavior is a behavioral feature that is particularly hard tomeasure and, hence, to studyaccuratelywithneuroimaging.Thiscould involvethetendency toovereator cramfood in themouth, indiscriminateeating, oral exploration of inanimate objects, increased selectivity in food choices, or a preference for sweet foods.7 These behaviors are typically best capturedwith caregiver questionnaires sincea lossof insight results inanunderestimationof the presence and severity of the behaviors by the patient. These questionnairesarenotperfect,however,andare limitedbyproblemswith overestimation or underestimation. In addition, the reduced quantitative scale often inherent to these questionnaires (eg,4-point scaleofnormal,mild,moderate, severe) can alsomake neuroimaging analyses difficult. In this issue of JAMA Neurology, Ahmed and colleagues8 aimed to overcome these difficulties by performing prospective well-controlled experiments to assess caloric intake and sucrose preference in patients with FTD, with the additional aimof assessingMRI correlates of performanceon these tests. An ad libitum test meal was used to assess caloric intake and an experiment involving tasting of desserts of varying sugar content was used to assess sucrose preference. These experimentswereperformed in 19patientswith thebehavioral variant of FTD (bvFTD) and 15 patients with semantic dementia (SD), aswell as in2control groupsconsistingof 15patientswith Alzheimer dementia and 25 healthy normal controls. All participants alsounderwent a3-TMRI.Theauthors found that caloric intake was only increased in the patients with bvFTD, while an increasedpreference for the sweetest dessertwasobserved in both bvFTD and SD. This increased preference for the sweetest dessert was not due to difficulty in perceiving sweetness since all groups could correctlyperceivewhichdesert was the sweetest. The MRI analysis was performed using voxel-basedmorphometryandvoxelwisegeneral linearmodel statistics to assess correlationsbetweenperformanceon these 2 tests and gray matter volume. A large number of overlapping regionswere found tocorrelatewithperformanceonboth tests.Within thebvFTDgroup, increasedcaloric intakewasassociatedwith regionsof loss extending fromthe temporal lobe (including inferior andmiddle temporal gyri and fusiform) to theoccipital lobe, aswell as the thalamus,hippocampus,parahippocampal gyrus, cingulate cortex, and cerebellum, particularly in the right hemisphere. These temporal regions and occipital lobe were also found to correlate with caloric intake in SD, although this analysis also identified a number of frontal regions, including the orbitofrontal cortex, and was more predominantly left sided. The correlation analysis for sucrose preference was performed across patients with bvFTD Related article page 282 Editorial Opinion

Eating behavior in frontotemporal dementia: Peripheral hormones vs hypothalamic pathology.

To contrast the relationships of hormonal eating peptides and hypothalamic volumes to eating behavior and metabolic changes (body mass index [BMI]) in behavioral variant frontotemporal dementia (bvFTD) and semantic variant primary progressive aphasia (svPPA). Seventy-five patients with dementia (19 bvFTD, 26 svPPA, and 30 Alzheimer disease dementia) and 23 controls underwent fasting blood analyses of leptin, ghrelin, cholecystokinin, peptide tyrosine tyrosine (PYY), and agouti-related peptide (AgRP) levels. On brain MRI anterior, posterior, and total hypothalamic volumes were measured. Relationships between endocrine measures, hypothalamic volumes, eating behaviors, and BMI were investigated. Levels of AgRP were higher in patients with bvFTD (69 ± 89 pg/mL) and svPPA (62 ± 81 pg/mL) compared with controls (23 ± 19 pg/mL, p < 0.01). No differences were found for leptin, oxytocin, cholecystokinin, ghrelin, and PYY levels. Patients with bvFTD and svPPA had higher scores on questionnaires measuring eating behaviors. Atrophy of the posterior and total hypothalamus was observed in the bvFTD group only. Linear regression modeling revealed that leptin and AgRP levels predicted BMI. Eating abnormalities are multifactorial in FTD. In bvFTD, they are in part related to hypothalamic degeneration, with potential disintegration of the network connections between the hypothalamus and orbitofrontal cortex/reward pathways. In svPPA, although hypothalamic volumes are preserved, this group experiences elevated AgRP levels similar to bvFTD, which predicts BMI in both groups. This finding highlights the potential key role of AgRP in eating and metabolic changes and provides a potential target for treatment to modify disease progression.

Characterizing Sexual Behavior in Frontotemporal Dementia.

Frontotemporal dementia (FTD) is characterized by a number of prominent behavioral changes. While FTD has been associated with the presence of aberrant or unusual sexual behaviors in a proportion of patients, few studies have formally investigated changes in sexual function in this disease. We aimed to systematically quantify changes in sexual behavior, including current symptoms and changes from prior diagnoses, in behavioral-variant (bvFTD) and semantic dementia (SD), compared to Alzheimer's disease (AD). Carers of 49 dementia patients (21 bvFTD, 11 SD, 17 AD) were interviewed using the Sexual Behavior and Intimacy Questionnaire (SIQ), a survey designed to assess changes in sexual function across multiple domains including initiating, level of affection, and aberrant or unusual sexual behavior. BvFTD patients show prominent hyposexual behavior including decreased affection, initiation, and response to advances by partners, and decreased frequency of sexual relations, compared to AD and to SD patients. The greatest changes in sexual behavior compared to pre-diagnoses were found in the bvFTD group with a 90-100% decrease in initiation, response, and frequency of sexual relations. Notably, aberrant or unusual sexual behavior was reported in a minority of bvFTD and SD patients and occurred in patients who also showed hyposexual behavior toward their partner. Overall loss of affection, reduced initiation of sexual activity, and responsiveness is an overwhelming feature of bvFTD. In contrast, aberrant or unusual sexual behavior is observed in the minority of bvFTD patients. The underlying pathophysiology of these changes likely reflects structural and functional changes in frontoinsular and limbic regions including the hypothalamus.

Criminal behavior in frontotemporal dementia and Alzheimer disease.

Neurodegenerative diseases can cause dysfunction of neural structures involved in judgment, executive function, emotional processing, sexual behavior, violence, and self-awareness. Such dysfunctions can lead to antisocial and criminal behavior that appears for the first time in the adult or middle-aged individual or even later in life. To investigate the frequency and type of criminal behavior among patients with a diagnosed dementing disorder. We conducted a retrospective medical record review of 2397 patients who were seen at the University of California, San Francisco, Memory and Aging Center between 1999 and 2012, including 545 patients with Alzheimer disease (AD), 171 patients with behavioral variant of frontotemporal dementia (bvFTD), 89 patients with semantic variant of primary progressive aphasia, and 30 patients with Huntington disease. Patient notes containing specific keywords denoting criminal behavior were reviewed. Data were stratified by criminal behavior type and diagnostic groups. Frequencies of criminal behavior and χ² statistics were calculated. Of the 2397 patients studied, 204 (8.5%) had a history of criminal behavior that emerged during their illness. Of the major diagnostic groups, 42 of 545 patients (7.7%) with AD, 64 of 171 patients (37.4%) with bvFTD, 24 of 89 patients (27.0%) with semantic variant of primary progressive aphasia, and 6 of 30 patients (20%) with Huntington disease exhibited criminal behavior. A total of 14% of patients with bvFTD were statistically significantly more likely to present with criminal behavior compared with 2% of patients with AD (P < .001) and 6.4% were statistically significantly more likely to exhibit violence compared with 2% of patients with AD (P = .003). Common manifestations of criminal behavior in the bvFTD group included theft, traffic violations, sexual advances, trespassing, and public urination in contrast with those in the AD group, who commonly committed traffic violations, often related to cognitive impairment. Criminal behavior is more common in patients with bvFTD and semantic variant of primary progressive aphasia than in those with AD and is more likely to be an early manifestation of the disorder. Judicial evaluations of criminality in the demented individual might require different criteria than the classic "insanity defense" used in the American legal system; these individuals should be treated differently by the law. The appearance of new-onset criminal behavior in an adult should elicit a search for frontal and anterior temporal brain disease and for dementing disorders.

Functional MRI of music emotion processing in frontotemporal dementia.

Frontotemporal dementia is an important neurodegenerative disorder of younger life led by profound emotional and social dysfunction. Here we used fMRI to assess brain mechanisms of music emotion processing in a cohort of patients with frontotemporal dementia (n = 15) in relation to healthy age-matched individuals (n = 11). In a passive-listening paradigm, we manipulated levels of emotion processing in simple arpeggio chords (mode versus dissonance) and emotion modality (music versus human emotional vocalizations). A complex profile of disease-associated functional alterations was identified with separable signatures of musical mode, emotion level, and emotion modality within a common, distributed brain network, including posterior and anterior superior temporal and inferior frontal cortices and dorsal brainstem effector nuclei. Separable functional signatures were identified post-hoc in patients with and without abnormal craving for music (musicophilia): a model for specific abnormal emotional behaviors in frontotemporal dementia. Our findings indicate the potential of music to delineate neural mechanisms of altered emotion processing in dementias, with implications for future disease tracking and therapeutic strategies.

Alterations in microRNA-124 and AMPA receptors contribute to social behavioral deficits in frontotemporal dementia.

Many neurodegenerative diseases, such as frontotemporal dementia (FTD), are associated with behavioral deficits, but the anatomical and molecular bases remain poorly understood. Here we show that forebrain-specific expression of FTD-associated mutant CHMP2B causes several age-dependent neurodegenerative phenotypes, including social behavioral impairments. The social deficits were accompanied by a change in AMPA receptor (AMPAR) composition, leading to imbalance between Ca2+-permeable and -impermeable AMPARs. Expression of most AMPAR subunits was regulated by the brain-enriched microRNA (miR-124), whose abundance was markedly decreased in the superficial layers of cerebral cortex of FTD mice. We found similar changes in miR-124 and AMPAR levels in the frontal cortex and iPSC-derived neurons of subjects with behavioral variant FTD. Moreover, miR-124 expression in the medial prefrontal cortex decreased AMPAR levels and partially rescued behavioral deficits. Knockdown of Gria2 also alleviated social impairments in FTD mice. Our results identify a novel mechanism involving miR-124 and AMAPRs in regulating social behavior in FTD and suggest a potential therapeutic avenue.

Clomipramine in the Treatment of Compulsive Behavior in Frontotemporal Dementia

Compulsive behaviors in patients with behavioral variant frontotemporal dementia (bvFTD) occur frequently and are challenging to manage. We report three cases of probable bvFTD associated with compulsive behaviors that responded well to treatment with clomipramine at daily dosages varying from 20 to 175 mg. The titration approach involved an initial 10-mg dose that was subsequently increased in 10 mg increments on a weekly basis until symptom relief without intolerable side effects. Our case series supports the consideration for a therapeutic trial with clomipramine in bvFTD when compulsive behavior occurs in these patients. It also highlights the need for further research on pharmacological treatments in bvFTD.

Observation of Social Behavior in Frontotemporal Dementia

The most characteristic manifestations of behavioral variant frontotemporal dementia (bvFTD) are abnormalities in social behavior. However, distinguishing bvFTD based on social behavior can be difficult in structured clinical settings. Using a Social Observation Inventory, 10 patients with bvFTD and 10 patients with Alzheimer's disease (AD) were compared to their caregiver interlocutors on 1-hour mealtime, in-home videotaped segments. Compared to caregivers and patients with AD, patients with bvFTD were significantly disturbed in social behavior. In contrast, patients with AD were indistinguishable from their caregivers. The lack of "you" comments and decreased tact and manners distinguished 92.6% of the patients with bvFTD from patients with AD and caregivers. The Social Observation Inventory scores correlated with scores on frontal-executive tests and socioemotional scales. The systematic observation of social behavior during routine activities may be one of the best ways to distinguish patients with bvFTD from normal individuals and from patients with other dementias.

Successful treatment of inappropriate sexual behavior in fronto-temporal dementia with MPA: a case report

Successful treatment of inappropriate sexual behavior in fronto-temporal dementia with MPA: a case report