Psychiatric Screening Measures in Behavioral Variant Frontotemporal Dementia.

OBJECTIVE: Behavioral variant frontotemporal dementia (bvFTD) is sometimes misdiagnosed as a primary psychiatric disorder, such as major depressive disorder, bipolar disorder, an anxiety disorder, autism spectrum disorder (ASD), or attention-deficit hyperactivity disorder (ADHD). Nonspecialists often use screening measures for primary psychiatric disorders in early assessments of persons with bvFTD. The investigators aimed to evaluate the manifestations of bvFTD in surveys intended to screen for primary psychiatric disorders. METHODS: Patients with bvFTD (N=27) presenting to an academic neurobehavior specialty clinic and their caregivers were provided questionnaire packets including the Mood Disorder Questionnaire (MDQ), the Patient Health Questionnaire-9 (PHQ-9), the Generalized Anxiety Disorder-7 scale (GAD-7), the Adult ADHD Self-Report Scale, version 1.1, the Ritvo Autism and Asperger Diagnostic Scale, and the Neuropsychiatric Inventory Questionnaire. Established cutoff scores suggesting the presence of a primary psychiatric disorder were used to define a "positive" response. Individual questions from each screening questionnaire were examined for a more granular characterization of bvFTD. RESULTS: Overall, 15% of bvFTD patients screened positive for bipolar disorder, 54% screened positive for ADHD, and 89% screened positive for ASD. Hyperactivity or hypersensitivity symptoms were infrequently endorsed. In addition, 57% of respondents screened positive for depressive symptoms on the PHQ-9, and 43% screened positive for anxiety symptoms on the GAD-7. CONCLUSIONS: The use of cutoff scores on screening measures for primary psychiatric disorders resulted in potentially problematic positive screens of primary psychiatric disorders among persons with bvFTD. Identifying specific questions that distinguish between bvFTD and primary psychiatric disorders requires further study.

Sleep and circadian rhythm disruptions in behavioral variant frontotemporal dementia.

INTRODUCTION: Sleep and rest-activity rhythm alterations are common in neurodegenerative diseases. However, their characterization in patients with behavioral variant frontotemporal dementia (bvFTD) has proven elusive. We investigated rest-activity rhythm alterations, sleep disturbances, and their neural correlates in bvFTD. METHODS: Twenty-seven bvFTD patients and 25 healthy controls completed sleep questionnaires and underwent 7 days of actigraphy while concurrently maintaining a sleep diary. Cortical complexity and thickness were calculated from T1-weighted magnetic resonance (MR) images. RESULTS: Compared to controls, bvFTD patients showed longer time in bed (95% confidence interval [CI]: 79.31, 321.83) and total sleep time (95% CI: 24.38, 321.88), lower sleep efficiency (95% CI: -12.58, -95.54), and rest-activity rhythm alterations in the morning and early afternoon. Increased sleep duration was associated with reduced cortical thickness in frontal regions. DISCUSSION: Patients with bvFTD showed longer sleep duration, lower sleep quality, and rest-activity rhythm alterations. Actigraphy could serve as a cost-effective and accessible tool for ecologically monitoring changes in sleep duration in bvFTD patients. HIGHLIGHTS: We assessed sleep and circadian rhythms in behavioral variant frontotemporal dementia (bvFTD) using actigraphy. Patients with bvFTD show increased sleep duration and reduced sleep quality. Patients with bvFTD show rest-activity alterations in the morning and early afternoon. Sleep duration is associated with reduced cortical thickness in frontal regions. These alterations may represent an early sign of neurodegeneration.

Social and non-social working memory in neurodegeneration.

Although social functioning relies on working memory, whether a social-specific mechanism exists remains unclear. This undermines the characterization of neurodegenerative conditions with both working memory and social deficits. We assessed working memory domain-specificity across behavioral, electrophysiological, and neuroimaging dimensions in 245 participants. A novel working memory task involving social and non-social stimuli with three load levels was assessed across controls and different neurodegenerative conditions with recognized impairments in: working memory and social cognition (behavioral-variant frontotemporal dementia); general cognition (Alzheimer's disease); and unspecific patterns (Parkinson's disease). We also examined resting-state theta oscillations and functional connectivity correlates of working memory domain-specificity. Results in controls and all groups together evidenced increased working memory demands for social stimuli associated with frontocinguloparietal theta oscillations and salience network connectivity. Canonical frontal theta oscillations and executive-default mode network anticorrelation indexed non-social stimuli. Behavioral-variant frontotemporal dementia presented generalized working memory deficits related to posterior theta oscillations, with social stimuli linked to salience network connectivity. In Alzheimer's disease, generalized working memory impairments were related to temporoparietal theta oscillations, with non-social stimuli linked to the executive network. Parkinson's disease showed spared working memory performance and canonical brain correlates. Findings support a social-specific working memory and related disease-selective pathophysiological mechanisms.

Brain Sagging Dementia.

PURPOSE OF REVIEW: Brain sagging dementia (BSD) is a rare but devastating form of early-onset dementia characterized by intracranial hypotension and behavioral changes resembling behavioral variant frontotemporal dementia. This review aims to provide a comprehensive overview of BSD, highlighting its pathomechanism, diagnostic tools, and available treatment options. RECENT FINDINGS: BSD exhibits a complex clinical manifestation with insidious onset and gradual progression of behavioral disinhibition, apathy, inertia, and speech alterations. Additionally, patients may exhibit brainstem and cerebellar signs such as hypersomnolence and gait disturbance. Although headaches are common, they may not always demonstrate typical orthostatic features. Recent radiological advances have improved the detection of CSF leaks, enabling targeted treatment and favorable outcomes. Understanding the pathomechanism and available diagnostic tools for BSD is crucial for a systematic approach to timely diagnosis and treatment of this reversible form of early-onset dementia, as patients often endure a complex and lengthy clinical course.

Measuring Antisocial Behaviors in Behavioral Variant Frontotemporal Dementia With a Novel Informant-Based Questionnaire.

OBJECTIVE: Antisocial behaviors are common and problematic among patients with behavioral variant frontotemporal dementia (bvFTD). In the present study, the investigators aimed to validate an informant-based questionnaire developed to measure the extent and severity of antisocial behaviors among patients with dementia. METHODS: The Social Behavior Questionnaire (SBQ) was developed to measure 26 antisocial behaviors on a scale from absent (0) to very severe (5). It was administered to 23 patients with bvFTD, 19 patients with Alzheimer's disease, and 14 patients with other frontotemporal lobar degeneration syndromes. Group-level differences in the presence and severity of antisocial behaviors were measured. Psychometric properties of the SBQ were assessed by using Cronbach's alpha, exploratory factor analysis, and comparisons with a psychopathy questionnaire. Cluster analysis was used to determine whether the SBQ identifies different subgroups of patients. RESULTS: Antisocial behaviors identified by using the SBQ were common and severe among patients with bvFTD, with at least one such behavior endorsed for 21 of 23 (91%) patients. Antisocial behaviors were more severe among patients with bvFTD, including the subsets of patients with milder cognitive impairment and milder disease severity, than among patients in the other groups. The SBQ was internally consistent (Cronbach's α=0.81). Exploratory factor analysis supported separate factors for aggressive and nonaggressive behaviors. Among the patients with bvFTD, the factor scores for aggressive behavior on the SBQ were correlated with those for antisocial behavior measured on the psychopathy scale, but the nonaggressive scores were not correlated with psychopathy scale measures. The k-means clustering analysis identified a subset of patients with severe antisocial behaviors. CONCLUSIONS: The SBQ is a useful tool to identify, characterize, and measure the severity of antisocial behaviors among patients with dementia.

Prenatal gyrification pattern affects age at onset in frontotemporal dementia.

The paracingulate sulcus is a tertiary sulcus formed during the third trimester. In healthy individuals paracingulate sulcation is more prevalent in the left hemisphere. The anterior cingulate and paracingulate gyri are focal points of neurodegeneration in behavioral variant frontotemporal dementia (bvFTD). This study aims to determine the prevalence and impact of paracingulate sulcation in bvFTD. Structural magnetic resonance images of individuals with bvFTD (n = 105, mean age 66.9 years), Alzheimer's disease (n = 92, 73.3), and healthy controls (n = 110, 62.4) were evaluated using standard protocol for hemispheric paracingulate sulcal presence. No difference in left hemisphere paracingulate sulcal frequency was observed between groups; 0.72, 0.79, and 0.70, respectively, in the bvFTD, Alzheimer's disease, and healthy control groups, (P = 0.3). A significant impact of right (but not left) hemispheric paracingulate sulcation on age at disease onset was identified in bvFTD (mean 60.4 years where absent vs. 63.8 where present [P = 0.04, Cohen's d = 0.42]). This relationship was not observed in Alzheimer's disease. These findings demonstrate a relationship between prenatal neuronal development and the expression of a neurodegenerative disease providing a gross morphological example of brain reserve.

Multidimensional inhibitory signatures of sentential negation in behavioral variant frontotemporal dementia.

BACKGROUND: Processing of linguistic negation has been associated to inhibitory brain mechanisms. However, no study has tapped this link via multimodal measures in patients with core inhibitory alterations, a critical approach to reveal direct neural correlates and potential disease markers. METHODS: Here we examined oscillatory, neuroanatomical, and functional connectivity signatures of a recently reported Go/No-go negation task in healthy controls and behavioral variant frontotemporal dementia (bvFTD) patients, typified by primary and generalized inhibitory disruptions. To test for specificity, we also recruited persons with Alzheimer's disease (AD), a disease involving frequent but nonprimary inhibitory deficits. RESULTS: In controls, negative sentences in the No-go condition distinctly involved frontocentral delta (2-3 Hz) suppression, a canonical inhibitory marker. In bvFTD patients, this modulation was selectively abolished and significantly correlated with the volume and functional connectivity of regions supporting inhibition (e.g. precentral gyrus, caudate nucleus, and cerebellum). Such canonical delta suppression was preserved in the AD group and associated with widespread anatomo-functional patterns across non-inhibitory regions. DISCUSSION: These findings suggest that negation hinges on the integrity and interaction of spatiotemporal inhibitory mechanisms. Moreover, our results reveal potential neurocognitive markers of bvFTD, opening a new agenda at the crossing of cognitive neuroscience and behavioral neurology.

Error profiles of facial emotion recognition in frontotemporal dementia and Alzheimer's disease.

OBJECTIVES: To identify the patterns of errors in facial emotion recognition in frontotemporal dementia (FTD) subtypes compared with Alzheimer's disease (AD) and healthy controls. DESIGN: Retrospective analysis. SETTING: Participants were recruited from FRONTIER, the frontotemporal dementia research group at the University of Sydney, Australia. PARTICIPANTS: A total of 356 participants (behavioral-variant FTD (bvFTD): 62, semantic dementia (SD)-left: 29, SD-right: 14, progressive non-fluent aphasia (PNFA): 21, AD: 76, controls: 90) were included. MEASUREMENTS: Facial emotion recognition was assessed using the Facial Affect Selection Task, a word-face matching task measuring recognition of the six basic emotions (anger, disgust, fear, happiness, sadness, and surprise), as well as neutral emotion, portrayed by black and white faces. RESULTS: Overall, all clinical groups performed significantly worse than controls with the exception of the PNFA subgroup (p = .051). The SD-right group scored worse than all other clinical groups (all p values < .027) and the bvFTD subgroup performed worse than the PNFA group (p < .001). The most frequent errors were in response to the facial emotions disgust (26.1%) and fear (22.9%). The primary error response to each target emotion was identified; patterns of errors were similar across all clinical groups. CONCLUSIONS: Facial emotion recognition is impaired in FTD and AD compared to healthy controls. Within FTD, bvFTD and SD-right are particularly impaired. Dementia groups cannot be distinguished based on error responses alone. Implications for future clinical diagnosis and research are discussed.

Multisite ALLFTD study modeling progressive empathy loss from the earliest stages of behavioral variant frontotemporal dementia.

INTRODUCTION: Empathy relies on fronto-cingular and temporal networks that are selectively vulnerable in behavioral variant frontotemporal dementia (bvFTD). This study modeled when in the disease process empathy changes begin, and how they progress. METHODS: Four hundred thirty-one individuals with asymptomatic genetic FTD (n = 114), genetic and sporadic bvFTD (n = 317), and 163 asymptomatic non-carrier controls were enrolled. In sub-samples, we investigated empathy measured by the informant-based Interpersonal Reactivity Index (IRI) at each disease stage and over time (n = 91), and its correspondence to underlying atrophy (n = 51). RESULTS: Empathic concern (estimate = 4.38, 95% confidence interval [CI] = 2.79, 5.97; p < 0.001) and perspective taking (estimate = 5.64, 95% CI = 3.81, 7.48; p < 0.001) scores declined between the asymptomatic and very mild symptomatic stages regardless of pathogenic variant status. More rapid loss of empathy corresponded with subcortical atrophy. DISCUSSION: Loss of empathy is an early and progressive symptom of bvFTD that is measurable by IRI informant ratings and can be used to monitor behavior in neuropsychiatry practice and treatment trials.

Interoception Primes Emotional Processing: Multimodal Evidence from Neurodegeneration.

Recent frameworks in cognitive neuroscience and behavioral neurology underscore interoceptive priors as core modulators of negative emotions. However, the field lacks experimental designs manipulating the priming of emotions via interoception and exploring their multimodal signatures in neurodegenerative models. Here, we designed a novel task that involves interoceptive and control-exteroceptive priming conditions followed by post-interoception and post-exteroception facial emotion recognition (FER). We recruited 114 participants, including healthy controls (HCs) as well as patients with behavioral variant frontotemporal dementia (bvFTD), Parkinson's disease (PD), and Alzheimer's disease (AD). We measured online EEG modulations of the heart-evoked potential (HEP), and associations with both brain structural and resting-state functional connectivity patterns. Behaviorally, post-interoception negative FER was enhanced in HCs but selectively disrupted in bvFTD and PD, with AD presenting generalized disruptions across emotion types. Only bvFTD presented impaired interoceptive accuracy. Increased HEP modulations during post-interoception negative FER was observed in HCs and AD, but not in bvFTD or PD patients. Across all groups, post-interoception negative FER correlated with the volume of the insula and the ACC. Also, negative FER was associated with functional connectivity along the (a) salience network in the post-interoception condition, and along the (b) executive network in the post-exteroception condition. These patterns were selectively disrupted in bvFTD (a) and PD (b), respectively. Our approach underscores the multidimensional impact of interoception on emotion, while revealing a specific pathophysiological marker of bvFTD. These findings inform a promising theoretical and clinical agenda in the fields of nteroception, emotion, allostasis, and neurodegeneration.SIGNIFICANCE STATEMENT We examined whether and how emotions are primed by interoceptive states combining multimodal measures in healthy controls and neurodegenerative models. In controls, negative emotion recognition and ongoing HEP modulations were increased after interoception. These patterns were selectively disrupted in patients with atrophy across key interoceptive-emotional regions (e.g., the insula and the cingulate in frontotemporal dementia, frontostriatal networks in Parkinson's disease), whereas persons with Alzheimer's disease presented generalized emotional processing abnormalities with preserved interoceptive mechanisms. The integration of both domains was associated with the volume and connectivity (salience network) of canonical interoceptive-emotional hubs, critically involving the insula and the anterior cingulate. Our study reveals multimodal markers of interoceptive-emotional priming, laying the groundwork for new agendas in cognitive neuroscience and behavioral neurology.

Influence of periaqueductal gray on other salience network nodes predicts social sensitivity.

The intrinsic connectivity of the salience network (SN) plays an important role in social behavior, however the directional influence that individual nodes have on each other has not yet been fully determined. In this study, we used spectral dynamic causal modeling to characterize the effective connectivity patterns in the SN for 44 healthy older adults and for 44 patients with behavioral variant frontotemporal dementia (bvFTD) who have focal SN dysfunction. We examined the relationship of SN effective connections with individuals' socioemotional sensitivity, using the revised self-monitoring scale, an informant-facing questionnaire that assesses sensitivity to expressive behavior. Overall, average SN effective connectivity for bvFTD patients differs from healthy older adults in cortical, hypothalamic, and thalamic nodes. For the majority of healthy individuals, strong periaqueductal gray (PAG) output to right cortical (p < .01) and thalamic nodes (p < .05), but not PAG output to other central pattern generators contributed to sensitivity to socioemotional cues. This effect did not exist for the majority of bvFTD patients; PAG output toward other SN nodes was weak, and this lack of output negatively influenced socioemotional sensitivity. Instead, input to the left vAI from other SN nodes supported patients' sensitivity to others' socioemotional behavior (p < .05), though less effectively. The key role of PAG output to cortical and thalamic nodes for socioemotional sensitivity suggests that its core functions, that is, generating autonomic changes in the body, and moreover representing the internal state of the body, is necessary for optimal social responsiveness, and its breakdown is central to bvFTD patients' social behavior deficits.

Differences in aphasia syndromes between progressive supranuclear palsy-Richardson's syndrome, behavioral variant frontotemporal dementia and Alzheimer's dementia.

Language impairments, hallmarks of speech/language variant progressive supranuclear palsy, also occur in Richardson's syndrome (PSP-RS). Impaired communication may interfere with daily activities. Therefore, assessment of language functions is crucial. It is uncertain whether the Aachen Aphasia Test (AAT) is practicable in PSP-RS, behavioral variant frontotemporal dementia (bvFTD) and Alzheimer's dementia (AD) and language deficits differ in these disorders. 28 PSP-RS, 24 AD, and 24 bvFTD patients were investigated using the AAT and the CERAD-Plus battery. 16-25% of all patients failed in AAT subtests for various reasons. The AAT syndrome algorithm diagnosed amnestic aphasia in 5 (23%) PSP-RS, 7 (36%) bvFTD and 6 (30%) AD patients, Broca aphasia in 1 PSP-RS and 1 bvFTD patient, Wernicke aphasia in 1 bvFTD and 3 (15%) AD patients. However, aphasic symptoms resembled non-fluent primary progressive aphasia in 14 PSP-RS patients. In up to 46% of PSP-RS patients, 61% of bvFTD and 64% of AD patients significant impairments were found in the AAT subtests spontaneous speech, written language, naming, language repetition, language comprehension and the Token subtest. The CERAD-Plus subtest semantic fluency revealed significant impairment in 81% of PSP-RS, 61% of bvFTD, 44% of AD patients, the phonemic fluency subtest in 31, 40 and 31%, respectively. In contrast to bvFTD and AD, severity of language impairment did not correlate with cognitive decline in PSP-RS. In summary, the patterns of aphasia differ between the diagnoses. Local frontal language networks might be impaired in PSP-RS, whereas in AD and bvFTD, more widespread neuropathology might underly language impairment.

Empathy and Impaired Socioemotional Self-Perception in Frontotemporal Dementia.

OBJECTIVE: Impaired empathy is a core feature of behavioral variant frontotemporal dementia (bvFTD). Patients with bvFTD are also prominently impaired in experiencing self-conscious emotions. The investigators explored whether impaired empathy in bvFTD, such as self-conscious emotions, may result from impaired self-consciousness in social situations (socioemotional self-perception). METHODS: This pilot study evaluated 25 patients with bvFTD and compared them with 25 patients with Alzheimer's disease who had comparable dementia severity. Their caregivers completed the Social Dysfunction Scale (SDS), which quantifies empathy, and an extensive intake interview that included questions regarding self-consciousness and insight. The patients completed two measures of self-perception in social situations, the Schutte Self-Report Emotional Intelligence Test (SSEIT) scale and the Embarrassability Scale (EMB). RESULTS: Caregivers of patients with bvFTD, but not of patients with Alzheimer's disease, reported a high correlation between significantly decreased empathy (SDS) and decreased self-consciousness (intake interview questions). Consistent with lack of insight, the patients with bvFTD, unlike the patients with Alzheimer's disease, did not report decreases on the SSEIT and EMB measures. CONCLUSIONS: These preliminary findings suggest that impaired socioemotional self-perception plays a role in the loss of empathy among patients with bvFTD. A lack of self-consciousness in social situations may contribute to a loss of empathy resulting from an inability to co-represent another's emotion in relation to oneself.

Pupillometry as an index for cognitive processing in behavioral variant FrontoTemporal Dementia: a series of case studies.

We investigated whether pupil size can variate with the intensity of cognitive processing in patients with behavioral-variant-Frontotemporal-Dementia (bvFTD). We invited five bvFTD participants and 21 controls to perform forward spans and backward spans, and, in a control condition, to count aloud. We recorded pupil activity using eye-tracking-glasses during the spans and control condition. Analysis demonstrated larger pupil sizes during backward spans than during forward spans, and larger pupil sizes during forward spans than during counting in both bvFTD and control participants. These findings demonstrate how increased cognitive load triggers increased pupil size and how this connection is maintained in bvFTD.

Hippocampal atrophy and intrinsic brain network dysfunction relate to alterations in mind wandering in neurodegeneration.

Mind wandering represents the human capacity for internally focused thought and relies upon the brain's default network and its interactions with attentional networks. Studies have characterized mind wandering in healthy people, yet there is limited understanding of how this capacity is affected in clinical populations. This paper used a validated thought-sampling task to probe mind wandering capacity in two neurodegenerative disorders: behavioral variant frontotemporal dementia [(bvFTD); n = 35] and Alzheimer's disease [(AD); n = 24], compared with older controls (n = 37). These patient groups were selected due to canonical structural and functional changes across sites of the default and frontoparietal networks and well-defined impairments in cognitive processes that support mind wandering. Relative to the controls, bvFTD patients displayed significantly reduced mind wandering capacity, offset by a significant increase in stimulus-bound thought. In contrast, AD patients demonstrated comparable levels of mind wandering to controls, in the context of a relatively subtle shift toward stimulus-/task-related forms of thought. In the patient groups, mind wandering was associated with gray matter integrity in the hippocampus/parahippocampus, striatum, insula, and orbitofrontal cortex. Resting-state functional connectivity revealed associations between mind wandering capacity and connectivity within and between regions of the frontoparietal and default networks with distinct patterns evident in patients vs. controls. These findings support a relationship between altered mind wandering capacity in neurodegenerative disorders and structural and functional integrity of the default and frontoparietal networks. This paper highlights a dimension of cognitive dysfunction not well documented in neurodegenerative disorders and validates current models of mind wandering in a clinical population.

Multidimensional Apathy in Behavioral Variant Frontotemporal Dementia, Primary Progressive Aphasia, and Alzheimer Disease.

Apathy is prevalent in dementia, such as behavioral variant frontotemporal dementia (bvFTD), primary progressive aphasia (PPA), and Alzheimer disease (AD). As a multidimensional construct, it can be assessed and subsumed under a Dimensional Apathy Framework. A consistent apathy profile in bvFTD and PPA has yet to be established. The aim was to explore apathy profiles and awareness in bvFTD, PPA, and AD. A total of 12 patients with bvFTD, 12 patients with PPA, 28 patients with AD, and 20 matched controls, as well as their informants/carers, were recruited. All participants completed the Dimensional Apathy Scale (DAS), assessing executive, emotional, and initiation apathy subtypes, a 1-dimensional apathy measure, depression measure, and functional and cognitive screens. Apathy subtype awareness was determined through DAS informant/carer and self-rating discrepancy. Apathy profile comparison showed patients with bvFTD had significantly higher emotional apathy than patients with AD (P < .01) and significantly higher apathy over all subtypes than patients with PPA (Ps < .05). Additionally, patients with bvFTD had significantly lower awareness for emotional apathy (P < .01) when compared to patients with AD and PPA. All patient groups had significant global apathy over all subtypes compared to controls. The emergent apathy profile for bvFTD seems to be emotional apathy (indifference or emotional/affective neutrality), with lower self-awareness in this subtype. Further, lower self-awareness for executive apathy (lack of motivation for planning, organization, or attention) differentiates bvFTD from PPA. Future research should investigate the cognitive and neural correlates as well as the practical impact of apathy subtypes.

The bvFTD phenocopy syndrome: a case study supported by repeated MRI, [18F]FDG-PET and pathological assessment.

A clinical syndrome with neuropsychiatric features of bvFTD without neuroimaging abnormalities and a lack of decline is a phenocopy of bvFTD (phFTD). Growing evidence suggests that psychological, psychiatric and environmental factors underlie phFTD. We describe a patient diagnosed with bvFTD prior to the revision of the diagnostic guidelines of FTD. Repeated neuroimaging was normal and there was no FTD pathology at autopsy, rejecting the diagnosis. We hypothesize on etiological factors that on hindsight might have played a role. This case report contributes to the understanding of phFTD and adds to the sparse literature of the postmortem assessment of phFTD.

Measuring Behavior and Social Cognition in FTLD.

Because changes to socioemotional cognition and behavior are an early and central symptom in many of the FTLD syndromes, an objective and standardized approach to patient identification and staging relies on availability of validated socioemotional measures. Such tests should reflect functioning in key selectively vulnerable brain networks central to socioemotional behavior, specifically the intrinsically connected networks underpinning salience (SN) and semantic appraisal (SAN). There have been many challenges to the development of appropriate tests for patients with the FTLD syndromes, including the difficulty of creating standardized evaluations for the highly idiosyncratic deficits caused by salience-driven attention impairments, the trade-off between behaviorally or psychophysiologically precise measures versus the need for easily administered measures that can scale to broader clinical contexts, and the complexities of measuring socioemotional behavior across linguistically and culturally diverse samples. A subset of available socioemotional tests are reviewed with respect to evidence for their ability to reflect structural and functional changes to the FTLD-specific SN and SAN networks, and their differential diagnostic utility in the neurodegenerative disease syndromes is discussed.

The Relationship between the Most Common Subtypes of Dementia and Orthostatic Hypotension in Older Adults.

BACKGROUND: It is crucial to evaluate the causes of morbidity and mortality in elderly patients with dementia, such as orthostatic hypotension (OH), which may affect their daily life activities, reduce the quality of life, and increase the caregiver burden. OBJECTIVE: We aimed to investigate the relationship between OH and the most common subtypes of dementia in detail. METHODS: A total of 268 older adults with dementia diagnosed with Alzheimer's disease (AD), dementia with Lewy bodies (DLB), vascular dementia (VaD), and behavioral variant frontotemporal dementia (bvFTD), and 539 older adults without dementia were included in this prospective study. Comprehensive geriatric assessment including comorbidity, medication evaluation, and the head-up tilt test was also performed. RESULTS: Of the participants, 13.8, 8.3, 6.4, and 4.8% had AD, DLB, bvFTD, and VaD, respectively. After adjusting for age, gender, the presence of comorbidities, and usage of OH-induced drugs; AD, DLB, and VaD were associated with OH (odds ratio [OR]: 2.23 confidence interval [CI] 95% 1.31-3.80; p = 0.003; OR: 3.68 CI 95% 1.98-6.83; p < 0.001, and OR: 3.56 CI 95% 1.46-8.69; p = 0.005, respectively). Furthermore, VaD was independently related to diastolic OH (OR: 4.19 CI 95% 1.66-10.57; p = 0.002), whereas AD and DLB were not. CONCLUSIONS: This study shows that elderly patients with DLB, AD, and VaD often have OH, a disabling autonomic dysfunction feature. Moreover, diastolic OH may play a role in the development of VaD. Therefore, considering potential complications of OH, it is essential to evaluate OH in the follow-up and management of those patients.

Neuropsychiatric Effects on Decision-Making in Early Alzheimer Disease.

BACKGROUND: Neuropsychiatric symptoms can impact decision-making in patients with Alzheimer disease (AD). METHODS: Using a simple decision-making task, a variant of the ultimatum game (UG) modified to control feelings of unfairness, this study investigated rejection responses among responders to unfair offers. The UG was administered to 11 patients with AD, 10 comparably demented patients with behavioral variant frontotemporal dementia (bvFTD), and 9 healthy controls (HC). The results were further compared with differences on the caregiver Neuropsychiatric Inventory (NPI). RESULTS: Overall, patients with AD significantly rejected more total offers than did the patients with bvFTD and the HC (P < .01). On the NPI, the only domain that was significantly worse among the patients with AD compared to the other groups was dysphoria/depression. CONCLUSIONS: These results suggest that early AD can be distinguished based on increased rejections of offers in decision-making, possibly consequent to a heightened sense of unfairness from dysphoria/depression.