The contribution of behavioral features to caregiver burden in FTLD spectrum disorders.

INTRODUCTION: Caregivers of patients with frontotemporal lobar degeneration (FTLD) spectrum disorders experience tremendous burden, which has been associated with the neuropsychiatric and behavioral features of the disorders. METHODS: In a sample of 558 participants with FTLD spectrum disorders, we performed multiple-variable regressions to identify the behavioral features that were most strongly associated with caregiver burden, as measured by the Zarit Burden Interview, at each stage of disease. RESULTS: Apathy and disinhibition, as rated by both clinicians and caregivers, as well as clinician-rated psychosis, showed the strongest associations with caregiver burden, a pattern that was consistent when participants were separated cross-sectionally by disease stage. In addition, behavioral features appeared to contribute most to caregiver burden in patients with early dementia. DISCUSSION: Caregivers should be provided with early education on the management of the behavioral features of FTLD spectrum disorders. Interventions targeting apathy, disinhibition, and psychosis may be most useful to reduce caregiver burden.

Links Between the C9orf72 Repeat Expansion and Psychiatric Symptoms.

PURPOSE OF REVIEW: To present recent findings on the links between the C9orf72 expansion and psychiatric impairment. RECENT FINDINGS: Repeat hexanucleotide expansions in the C9orf72 gene are a cause of familial frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), and the mixed phenotype, FTD-ALS. Symptomatic expansion carriers display higher rates of psychotic and other psychiatric symptoms than non-carriers. Neuroanatomical associations of these symptoms have been found in cortical and subcortical areas. Family members of symptomatic carriers have higher rates of primary neuropsychiatric disorders than control populations, and the C9orf72 expansion may contribute to this association. However, the expansion does not appear to directly cause primary psychiatric disorders. While there is strong evidence associating the C9orf72 expansion with psychotic symptoms in carriers and psychiatric disorders in their kindreds, the link between these two phenomena, if any, remains unclear.

Psychiatric symptoms in preclinical behavioural-variant frontotemporal dementia in MAPT mutation carriers.

OBJECTIVE: To characterise psychiatric symptoms in preclinical and early behavioural-variant frontotemporal dementia (bvFTD), a neurodegenerative disorder whose symptoms overlap with and are often mistaken for psychiatric illness. METHODS: The present study reports findings from a systematic, global, prospective evaluation of psychiatric symptoms in 12 preclinical carriers of pathogenic MAPT mutations, not yet meeting bvFTD diagnostic criteria, and 46 familial non-carrier controls. Current psychiatric symptoms, informant-reported symptoms and lifetime prevalence of psychiatric disorders were assessed with The Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) and the Neuropsychiatric Inventory Questionnaire. Fisher exact test was used to compare carriers and non-carriers' lifetime prevalence of six DSM-IV disorders: major depressive disorder, panic attacks, alcohol abuse, generalised anxiety disorder, panic disorder, and depressive disorder not otherwise specified. Other DSM-IV disorders had insufficient prevalence across our sample for between-group comparisons, but are reported. RESULTS: Non-carriers had greater prevalence of mood and anxiety disorders than has been reported for a general reference population. Preclinical carriers had lower lifetime prevalence of mood and anxiety disorders than non-carriers, except for depressive disorder not otherwise specified, an atypical syndrome comprising clinically significant depressive symptoms which fail to meet criteria for major depressive disorder. CONCLUSION: Findings suggest that early psychiatric symptoms of emergent bvFTD may manifest as emotional blunting or mood changes not cleanly conforming to criteria for a DSM-defined mood disorder.

Establishing dimensionality of sexual behaviours in patients with regional brain dysfunction.

OBJECTIVE: To develop a validated, caregiver-based measurement scale to assess sexual changes across several domains in a sample of 86 patients with penetrating traumatic brain injury (TBI) and 65 patients with neurodegeneration due to frontotemporal dementia and corticobasal syndrome. METHODS: A new measure, the Sexual Symptoms in Neurological Illness and Injury Questionnaire (SNIQ), was constructed. Dimensionality, monotonicity, item discrimination power, and scalability were evaluated using nonparametric Mokken item response theory (IRT) methodology. RESULTS: Three primary domains were established. The domains presented with sufficient reliability (rho .70 to .80), while meeting the Mokken IRT criteria of medium scalability. The domains were labeled 'Prosocial sexual behaviour' (H = .42), 'Sexual interest' (H = .50), and 'Inappropriate sexual behaviour' (H = .41). A fourth dimension emerged, 'Detachment' (H = .47), but with very few items. CONCLUSIONS: Construct validity was established for groups of items pertaining to three unique aspects of sexuality. These findings support further use of the SNIQ in assessing and researching sexual behaviours in patients with dementia and brain injury.

Modulating what is and what could have been: The effect of transcranial direct current stimulation on the evaluation of attained and unattained decision outcomes.

The affective evaluation of decision outcomes, whether attained (e.g., disappointment) or based on the conscious realization that a decision made differently would have led to a better or worse outcome (e.g., regret), greatly influence future decisions. Prior research has demonstrated a role of the medial and orbitofrontal cortex (M/OFC) in decision valuation and the experience of regret and relief. Here we examined whether inhibitory transcranial direct current stimulation (tDCS) could dampen the experience of decision-induced affect, with a focus on regret and relief. Thirty-eight participants completed a previously used gambling task and were asked to rate their happiness with attained outcomes of a chosen gamble before and after being shown unattained, counterfactual outcomes (i.e., what would have happened had they selected the other gamble). The difference in happiness rating before and after revealing these unattained counterfactual outcomes was taken as a measure of regret (negative shift) or relief (positive shift). During this task, 20 participants received 2 mA cathodal tDCS over EEG coordinate Fp1 for 20 minutes, and 18 participants received sham stimulation over the same location. Linear mixed-model results showed that, compared to sham, participants who received cathodal tDCS reported less intense emotions in response to attained as well as counterfactual outcomes. These findings were not due to the groups differing in the gambles they selected or attained monetary outcomes, demonstrating that tDCS can modulate decision-induced (counterfactual) affect. This may have implications for the ability to modulate value-based decision-making using brain stimulation techniques more broadly.

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

BACKGROUND: Changes in sexual behaviors in frontotemporal dementia (FTD) are common and multifaceted, but not well characterized. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.