Background and purpose Predicting the course of behavioural variant frontotemporal dementia (bvFTD) remains a major clinical challenge. This study aimed to identify factors that predict survival and clinical progression in bvFTD. Methods Consecutive patients with clinically probable bvFTD were prospectively followed up over an 8‐year period. Baseline neuropsychological variables, presence of a known pathogenic frontotemporal dementia gene mutation and a systematic visual magnetic resonance imaging assessment at baseline were examined as candidate predictors using multivariate modelling. Results After screening 121 cases, the study cohort consisted of 75 patients with probable bvFTD, with a mean age of 60.8 ± 8.5 years, followed up for a mean duration of 7.2 ± 3.5 years from symptom onset. Median survival time from disease onset was 10.8 years and median survival, prior to transition to nursing home, was 8.9 years. A total of 25 of the 75 patients died during the study follow‐up period. Survival without dependence was predicted by shorter disease duration at presentation (hazard ratio, 0.49, P = 0.001), greater atrophy in the anterior cingulate cortex (hazard ratio, 1.75, P = 0.047), older age (hazard ratio, 1.07, P = 0.026) and a higher burden of behavioural symptoms (hazard ratio, 1.04, P = 0.015). In terms of disease progression, presence of a known pathogenic frontotemporal dementia mutation (β = 0.46, P < 0.001) was the strongest predictor of progression. Deficits in letter fluency (β = −0.43, P = 0.017) and greater atrophy in the motor cortex (β = 0.51, P = 0.03) were also associated with faster progression. Conclusions This study provides novel clinical predictors of survival and progression in bvFTD. Our findings are likely to have an impact on prognostication and care planning in this difficult disease.

Background: Major prevention trials for Alzheimer's disease (AD) are now focusing on multidomain lifestyle interventions. However, the exact combination of behavioral factors related to AD pathology remains unclear. In two cohorts of cognitively unimpaired individuals at risk of AD, we examined which combinations of personality traits, neuropsychiatric symptoms, and cognitive lifestyle (years of education or lifetime cognitive activity) related to the pathological hallmarks of AD, amyloid-beta and tau deposits.Methods: Some 115 older adults with a parental or multiple-sibling family history of sporadic AD (PREVENT-AD cohort) underwent amyloid and tau positron emission tomography (PET) and answered several questionnaires related to behavioral attributes. Separately, we studied 117 mutation carriers from the Dominantly Inherited AD (DIAN) cohort with amyloid PET and behavioral data. Using partial least squares analysis, we identified latent variables relating amyloid or tau pathology with combinations of personality traits, neuropsychiatric symptoms, and cognitive lifestyle. Results:In PREVENT-AD, lower neuroticism, neuropsychiatric burden and higher education were associated with less amyloid deposition (p=0.014). Lower neuroticism and neuropsychiatric features, along with higher measures of openness and extraversion, were related to less tau deposition (p=0.006). In DIAN, lower neuropsychiatric burden and higher education were also associated with less amyloid (p=0.005). The combination of these factors accounted for up to 14% of AD pathology. Conclusions:In the preclinical phase of both sporadic and autosomal dominant AD, multiple behavioral features were associated with AD pathology. These results may suggest potential pathways by which multi-domain interventions might help delay AD onset or progression.

Objective: Amyotrophic lateral sclerosis (ALS) is a multisystem neurodegenerative disorder which includes cognitive and behavioural symptoms akin to frontotemporal dementia (FTD).Despite the necessity of caregiver intervention to assist with the management of cognitive and behavioural symptoms, there has been a lack of research on the topic. A focus on caregiver coping may offer a promising foundation to guide the development of interventions as part of ALS care. Accordingly, the aim of the present study was to examine the relationships between caregiver coping, psychological morbidity and burden of care in the context of ALS cognitive and behavioural symptoms.Methods: Fifty-five patient-caregiver dyads were recruited from specialised ALS and FTD clinics. Specific coping strategies were examined using the COPE Inventory/Brief COPE and psychological morbidity and burden were assessed using the Depression, Anxiety, and Stress Scale-21 and Zarit Burden Interview. The relationship between coping, psychological morbidity and burden of care were analysed using univariate and multivariate methods.Results: High-burden caregivers were more likely to be caring for patients with a diagnosis of ALS-FTD (p =.0001). Caregivers used problem-focused strategies (particularly planning) more frequently (M=71.4, SD=15.3) compared to emotion-focused (M=60.8, SD=12.3) and dysfunctional coping strategies (M=42.2, SD=8.6). A diagnosis of ALS-FTD (p=.0001) and problem-focused strategies (p=.024) emerged as significant predictors of caregiver burden.Caregiver anxiety, depression and stress were not predictive of caregiver burden (p=.151).Conclusions: Timely provision of caregiver support optimising problem-focused coping strategies as part of multidisciplinary ALS care, particularly for caregivers of ALS-FTD patients may mitigate caregiver burden.

Objective: Differentiating the primary progressive aphasia (PPA) variants in clinical settings remains complex and challenging, especially for the logopenic (lv-PPA) and nonfluent variants (nfv-PPA). Recent studies suggest that visuospatial memory is more compromised in lv-PPA than in nfv-PPA and is relatively spared in the semantic variant (sv-PPA). Accordingly, assessment of visuospatial memory performance may assist in the differential diagnosis of PPA variants. Here, we investigated the utility of a novel computerised visuospatial working memory test-the Box Task-to differentiate the three PPA variants and typical Alzheimer's disease (AD).Methods: Eighteen lv-PPA, 14 nfv-PPA, 23 sv-PPA, 33 AD patients, and 32 healthy controls matched for age and education were recruited. All participants completed the computerised Box Task and WMS-III Spatial Span as measures of visuospatial working memory. Results:The lv-PPA group made significantly more Box Task between-search errors than nfv-PPA, sv-PPA and control groups. The AD group, however, displayed the greatest impairments on this measure relative to the PPA variants. Logistic regression analyses in lv-PPA and nfv-PPA demonstrated that the combination of Box Task between-search error variables (i.e., 4-and 6-box levels) could correctly classify 72% of lv-PPA patients and nearly 79% of nfv-PPA patients. Area under the receiver operator characteristics curve (AUC) analyses revealed the Box Task was more sensitive than Spatial Span at differentiating lv-PPA from nfv-PPA. Conclusions:Our findings suggest that a simple, computerised measure of visuospatial working memory-the Box Task-shows potential diagnostic utility in differentiating lv-PPA from the other PPA variants.