Implementation of the MiNDToolkit intervention for the management of behavioral symptoms in MND by healthcare professionals: a mixed-methods process evaluation.

OBJECTIVE: MiNDToolkit is a novel psychoeducational intervention for carers to support management of behavioral symptoms in people living with motor neuron disease (PlwMND). Implementation of MiNDToolkit involves delivery of an online intervention to carers, which is reinforced by trained healthcare professionals (HCPs). METHODS: A mixed-methods process evaluation of the MiNDToolkit feasibility trial was conducted, focusing on reinforcement of the intervention by HCPs. Quantitative data, descriptively analyzed, were included from platform analytics, questionnaire, and 10 semi-structured interviews with HCPs. Interviews were transcribed verbatim; data were inductively analyzed using Reflective Thematic Analysis. RESULTS: The MiNDToolkit training and platform is a beneficial and acceptable resource for HCPs with potential to increase knowledge and confidence in identifying and managing behavioral symptoms in MND. Implementation barriers included HCPs' perceptions that highlighting behavior changes would be burdensome to carers and assumptions that carers would take the initiative to ask for support from clinicians. Degree of intervention reinforcement varied, with most HCPs delegating intervention delivery solely to the online platform. CONCLUSIONS: Implementation of the MiNDToolkit was viewed to be feasible and the platform thought to increase accessibility of support to carers. The flexible approach to delivery (online platform and optional HCP reinforcement) is acceptable as an intervention for supporting carers of PlwMND with behavioral symptoms. However, MiNDToolkit should not negate HCP involvement in providing medical and practical information to PlwMND and families. Future research should explore ways to incorporate support for carers in the management of PlwMND alongside standard care, alongside tools such as the MiNDToolkit.

An online intervention for carers to manage behavioral symptoms in motor neuron disease (MiNDToolkit): a randomized parallel multi-center feasibility trial.

BACKGROUND: Evidence on management of behavioral symptoms in motor neuron disease (MND) is lacking. The MiNDToolkit, an online psychoeducational platform, supports carers dealing with behavioral symptoms (BehSymp). The study objectives were to ascertain recruitment and retention rates, carer and healthcare professional (HCP) use of the platform, and completion of online assessments, to inform a full-scale trial. Design: Randomized, parallel, multi-center, feasibility trial. SETTING: England and Wales, across diverse MND services; recruitment from July/21 to November/22; last participant follow-up in March/23. PARTICIPANTS: Carers of people with motor neuron disease (PwMND) with BehSymp, recruited through MND services. After confirming eligibility, participants completed screening and baseline assessments online via the MiNDToolkit platform and were randomized centrally in a 1:1 ratio to MiNDToolkit or control. INTERVENTION: MiNDToolkit offered tailored modules to carers for the 3-month study period. Carers in the intervention group could receive additional support from MiNDToolkit trained HCPs. The control group was offered access to the intervention at the end of the study. Data were collected on platform usage and psychosocial variables. MAIN OUTCOMES: One hundred and fifty-one carers from 11 sites were invited to join the study (letter, face-to-face); 30 were screened; 29 were randomized. Fifteen people were allocated to the control arm; 14 to intervention. Carers were mostly female; median age for was 62.5 (IQR: 58, 68; intervention) and 57 (IQR: 56, 70; controls). Study retention was high (24/29 = 82.76%); carers engaged with the platform on average 14 times (median (IQR):14.0 (10.0, 18.5)) during the study period. CONCLUSION: The MiNDToolkit study was feasible and well accepted by carers and trained HCPs. A definitive trial is warranted.

Suitability of memory aids and strategies for people with posterior cortical atrophy: protocol for a scoping review.

BACKGROUND: Posterior cortical atrophy (PCA) is a neurodegenerative syndrome characterised by progressive visuospatial and visuoperceptual impairment. Recent research shows that memory impairment can also occur as an early symptom of the condition and that the impairment can be ameliorated by providing support in the memory recall phase, for example, by presenting a related cue. In Alzheimer's disease (AD), which is defined by an amnestic syndrome, memory aids and strategies have been used to help support everyday memory, which in turn can have a positive impact on patient and carer outcomes. Similar support for PCA could be achieved by using memory aids and strategies which help to encode and/or retrieve information, yet there are currently no guidelines for memory strategies that may be suitable in PCA. Due to the central visual disorder that defines PCA, careful consideration is needed when making recommendations. METHODS: A scoping review will be conducted of published studies that have assessed memory aids and strategies in people with AD and related dementias where memory is considered a core or supplementary feature, with the aim of distinguishing those that may be suitable or adaptable for PCA. The systematic search will include the electronic databases MEDLINE, PsycINFO and CINAHL, using search terms for dementia and memory aids and strategies identified in pilot searches. Findings will be mapped and described based on methods used, population, clinical data and memory aids and strategies identified. DISCUSSION: The scoping review will give an overview of the memory aids and strategies used in people with AD and related dementias and identify characteristics, modality and pragmatics to evaluate their suitability and adaptability for a PCA population. Tailored memory support strategies for people living with PCA could improve memory performance, with knock-on positive effects on patient and carer outcomes.

The behavioural variant frontotemporal dementia phenocopy syndrome is a distinct entity - evidence from a longitudinal study.

BACKGROUND: This study aimed to i) examine the frequency of C9orf72 expansions in a cohort of patients with the behavioural variant frontotemporal dementia (bvFTD) phenocopy syndrome, ii) observe outcomes in a group of phenocopy syndrome with very long term follow-up and iii) compare progression in a cohort of patients with the phenocopy syndrome to a cohort of patients with probable bvFTD. METHODS: Blood was obtained from 16 phenocopy cases. All met criteria for possible bvFTD and were labeled as phenocopy cases if they showed no functional decline, normal cognitive performance on the Addenbrooke's Cognitive Examination-Revised (ACE-R) and a lack of atrophy on brain imaging, over at least 3 years of follow-up. In addition, we obtained very long term follow-up data in 6 cases. A mixed model analysis approach determined the pattern of change in cognition and behaviour over time in phenocopy cases compared to 27 probable bvFTD cases. RESULTS: All 16 patients were screened for the C9orf72 expansion that was present in only one (6.25%). Of the 6 cases available for very long-term follow-up (13 - 21 years) none showed progression to frank dementia. Moreover, there was a decrease in the caregiver ratings of behavioural symptoms over time. Phenocopy cases showed significantly slower rates of progression compared to probable bvFTD patients (p < 0.006). CONCLUSION: The vast majority of patients with the bvFTD phenocopy syndrome remain stable over many years. An occasional patient can harbor the C9orf72 expansion. The aetiology of the remaining cases remains unknown but it appears very unlikely to reflect a neurodegenerative syndrome due to lack of clinical progression or atrophy on imaging.

Adaptación y validación de la Frontotemporal Dementia Rating Scale (FTD-FRS) al castellano / Adaptation and validation of a Spanish-language version of the Frontotemporal Dementia Rating Scale (FTD-FRS)

Introducción: La Frontotemporal Dementia Rating Scale (FTD-FRS) es una escala diseñada para facilitar la estadificación clínica y la evaluación de la progresión de pacientes con demencia frontotemporal (DFT). Objetivo: Realizar un estudio multicéntrico de adaptación y validación al castellano de la FTD-FRS. Metodología: La adaptación se realizó mediante 2 procesos de traducción y retrotraducción inglés-español español-inglés y se verificó con los autores originales. El proceso de validación se llevó a cabo en una muestra consecutiva de pacientes diagnosticados de DFT. Se evaluó la consistencia interna, se determinó la unidimensionalidad con el método Rasch, se analizaron la validez de constructo y la validez discriminante, y se calculó el grado de acuerdo entre la Clinical Dementia Rating scale y la FTD-FRS para los casos con DFT. Resultados: Se incluyeron 60 pacientes con DFT. La puntuación media de la FTD-FRS fue de 12,1 puntos (DE = 6,5; rango = 2-25) mostrando diferencias intergrupos (F = 120,3; gl = 3; p < 0,001). El α de Cronbach = 0,897, el análisis de componentes principales de los residuos produjo un aceptable autovalor para 5 contrastes (1,6-2,7) y una varianza respecto al origen del 36,1%. La FTD-FRS correlacionó con el Mini-mental test (r = 0,572; p < 0,001) y capacidad funcional (DAD; r = 0,790; p < 0,001). La FTD-FRS correlacionó significativamente con la Clinical Dementia Rating scale (r = −0,641; p < 0,001) pero se observó variabilidad entre la distribución de la gravedad, siendo valorados como más leves según la Clinical Dementia Rating scale que con la FTD-FRS (kappa = 0,055). Conclusiones: El estudio de traducción y validación al español mostró resultados de validez y unidimensionalidad (gravedad) satisfactorios para el uso de la FTD-FRS en el estudio de la gravedad en pacientes con DFT (AU)

Introduction: The Frontotemporal Dementia Rating Scale (FTD-FRS) is a tool designed to aid with clinical staging and assessment of the progression of frontotemporal dementia (FTD-FRS). Objective: Present a multicentre adaptation and validation study of a Spanish version of the FRS. Methodology: The adapted version was created using 2 translation-back translation processes (English to Spanish, Spanish to English) and verified by the scale's original authors. We validated the adapted version in a sample of consecutive patients diagnosed with FTD. The procedure included evaluating internal consistency, testing unidimensionality with the Rasch model, analysing construct validity and discriminant validity, and calculating the degree of agreement between the Clinical Dementia Rating scale (CDR) and FTD-FRS for FTD cases. Results: The study included 60 patients with DFT. The mean score on the FRS was 12.1 points (SD = 6.5; range, 2-25) with inter-group differences (F = 120.3; df = 3; P < .001). Cronbach's alpha was 0.897 and principal component analysis of residuals delivered an acceptable eigenvalue for 5 contrasts (1.6-2.7) and 36.1% raw variance. FRS was correlated with the Mini-mental State Examination (r = 0.572; P < .001) and functional capacity (DAD; r = 0.790; P < .001). FTD-FRS also showed a significant correlation with CDR (r = −0.641; P < .001), but we did observe variability in the severity levels; cases appeared to be less severe according to the CDR than when measured with the FTD-FRS (kappa = 0.055). Conclusions: This process of validating the Spanish translation of the FTD-FRS yielded satisfactory results for validity and unidimensionality (severity) in the assessment of patients with FTD (AU)

Adaptation and validation of a Spanish-language version of the Frontotemporal Dementia Rating Scale (FTD-FRS). / Adaptación y validación de la Frontotemporal Dementia Rating Scale (FTD-FRS) al castellano.

INTRODUCTION: The Frontotemporal Dementia Rating Scale (FTD-FRS) is a tool designed to aid with clinical staging and assessment of the progression of frontotemporal dementia (FTD-FRS). OBJECTIVE: Present a multicentre adaptation and validation study of a Spanish version of the FRS. METHODOLOGY: The adapted version was created using 2 translation-back translation processes (English to Spanish, Spanish to English) and verified by the scale's original authors. We validated the adapted version in a sample of consecutive patients diagnosed with FTD. The procedure included evaluating internal consistency, testing unidimensionality with the Rasch model, analysing construct validity and discriminant validity, and calculating the degree of agreement between the Clinical Dementia Rating scale (CDR) and FTD-FRS for FTD cases. RESULTS: The study included 60 patients with DFT. The mean score on the FRS was 12.1 points (SD=6.5; range, 2-25) with inter-group differences (F=120.3; df=3; P<.001). Cronbach's alpha was 0.897 and principal component analysis of residuals delivered an acceptable eigenvalue for 5 contrasts (1.6-2.7) and 36.1% raw variance. FRS was correlated with the Mini-mental State Examination (r=0.572; P<.001) and functional capacity (DAD; r=0.790; P<.001). FTD-FRS also showed a significant correlation with CDR (r=-0.641; P<.001), but we did observe variability in the severity levels; cases appeared to be less severe according to the CDR than when measured with the FTD-FRS (kappa=0.055). CONCLUSIONS: This process of validating the Spanish translation of the FTD-FRS yielded satisfactory results for validity and unidimensionality (severity) in the assessment of patients with FTD.

Apathy is associated with poor prognosis in amyotrophic lateral sclerosis.

BACKGROUND AND PURPOSE: Apathy is the most commonly reported behavioural change in amyotrophic lateral sclerosis (ALS). However, the degree to which it affects prognosis and overlaps with depression in this population is unknown. The present study examined the relationship between level of apathy, mortality and survival time and whether apathy was linked to specific symptom clusters of depression. METHODS: A cohort of 76 consecutive ALS patients attending specialized multidisciplinary clinics were classified according to level of apathy. The effects of clinical factors and apathy on survival time were analysed using univariate and multivariate methods. RESULTS: The majority of patients with moderate to severe apathy died during the study (P = 0.003) and had a median survival time of 21.7 months, considerably shorter than patients with mild apathy (46.9 months) and no apathy (51.9 months) (P = 0.0001). Apathy remained a significant predictor of survival even after controlling for clinical factors and symptom duration at the time of study entry (hazard ratio 3.8, 95% confidence interval 1.9-7.5, P = 0.0001). Depression with demoralization was not associated with level of apathy (P = 0.172) whereas depression with anhedonia was more common in patients with apathy than in those without apathy (P = 0.006). CONCLUSIONS: The presence of severe apathy is an independent, negative prognostic factor in ALS.

Motor function and behaviour across the ALS-FTD spectrum.

BACKGROUND: Behavioural/functional disturbances, characteristic of frontotemporal dementia (FTD), are also a feature of amyotrophic lateral sclerosis (ALS) and patients with combined ALS and FTD (FTD-ALS). AIM OF THE STUDY: To investigate the progression of behavioural disturbances in ALS and FTD using the FTD functional rating scale (FTDFRS). METHODS: Patients with ALS, FTD-ALS and FTD were recruited from specialist clinics. Baseline assessments included the FTDFRS and the ALS functional rating scale-revised (ALSFRS-R). Baseline assessments were included, as were longitudinal assessments in a proportion of patients. RESULTS: In total, 21 ALS, 12 FTD-ALS and 14 behavioural variant FTD (bvFTD) patients were included in the study. Moderate or severe behavioural disturbance was common in patients with ALS at baseline (47.6%), although less frequent than in bvFTD patients; patients with FTD-ALS displayed intermediate impairment. The ALSFRS-R showed the opposite pattern and did not correlate with the FTDFRS. During the follow-up period, significant (P < 0.05) behavioural deterioration was demonstrated in patients with bvFTD and FTD-ALS, with a trend for decline in patients with ALS (P = 0.06). CONCLUSION: Motor disturbance is the primary marker of disease severity in ALS, but behavioural and functional impairment are common, and may decline independently of motor function. As such, the FTDFRS may provide valuable information in the assessment and monitoring of ALS.

Body mass index delineates ALS from FTD: implications for metabolic health.

Weight loss and catabolic changes are increasingly recognized as factors that influence outcomes in patients with amyotrophic lateral sclerosis (ALS). An association between disease progression and low BMI has been reported in ALS; however, it remains unknown whether low BMI occurs across all forms of ALS and whether BMI changes with the development of cognitive impairment across the spectrum between ALS and frontotemporal dementia (FTD). One hundred and three ALS patients (56 limb predominant, 18 bulbar predominant, 13 ALS plus, 16 ALSFTD) were recruited and compared to 19 behavioral variant FTD (bvFTD) patients and a group of age-matched healthy controls. BMI was measured at the initial clinical visit. Patients were characterized as underweight, normal, overweight or obese, based on the current World Health Organization (WHO) guidelines. Limb and bulbar ALS patients had significantly lower BMI than ALS plus, ALSFTD, and bvFTD patient groups. When BMI was categorized using WHO guidelines the majority of the limb and bulbar ALS patients were either underweight or normal weight, whilst the majority of the ALS plus, ALSFTD and bvFTD patients were either overweight or obese. On follow-up BMI assessment the limb and bulbar groups tended to decline whilst ALS plus, ALSFTD and bvFTD groups remained stable or increased. BMI is significantly higher in ALS individuals with cognitive deficits. The present findings have prognostic implications for disease progression and may help delineate the metabolic profile across the ALSFTD spectrum.

Use of the Tailored Activities Program to reduce neuropsychiatric behaviors in dementia: an Australian protocol for a randomized trial to evaluate its effectiveness.

BACKGROUND: Behavioral and psychological symptoms of dementia (BPSD) are often considered to be the greatest challenge in dementia care, leading to increased healthcare costs, caregiver burden, and placement into care facilities. With potential for pharmacological intervention to exacerbate behaviors or even lead to mortality, the development and rigorous testing of non-pharmacological interventions is vital. A pilot of the Tailored Activities Program (TAP) for reducing problem behaviors in people with dementia was conducted in the United States with promising results. This randomized trial will investigate the effectiveness of TAP for reducing the burden of BPSD on persons with dementia and family caregivers within an Australian population. This trial will also examine the cost-effectiveness and willingness to pay for TAP compared with a control group. METHODS: This randomized trial aims to recruit 180 participant dyads of a person with dementia and their caregivers. Participants will have a diagnosis of dementia, exhibit behaviors as scored by the Neuropsychiatric Inventory, and the caregiver must have at least 7 h per week contact. Participants will be randomly allocated to intervention (TAP) or control (phone-based education sessions) groups, both provided by a trained occupational therapist. Primary outcome measure will be the revised Neuropsychiatric Inventory - Clinician rating scale (NPI-C) to measure BPSD exhibited by the person with dementia. CONCLUSIONS: This trial investigates the effectiveness and cost-effectiveness of TAP within an Australian population. Results will address a significant gap in the current Australian community-support base for people living with dementia and their caregivers.

Disability in atypical parkinsonian syndromes is more dependent on memory dysfunction than motor symptoms.

BACKGROUND: There is a gap in the systematic description and investigation of functional disability in corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP). Additionally, the relations between disability, apraxia, cognitive and behavioural changes are not well understood in atypical parkinsonian syndromes. METHODS: Fifty patients were included in this study (CBS = 18; PSP = 11), including a subgroup of primary progressive aphasia-nonfluent variant (PPA-nfv = 21) who were used as a control group given the clinic-pathological overlap. Functional disability (basic and instrumental activities of daily living), general cognition and behavioural changes were evaluated at baseline, with a subgroup of patients being reassessed after 16 months. RESULTS: The corticobasal syndrome group had the most marked disability in basic activities in comparison to progressive supranuclear palsy and primary progressive aphasia-nonfluent variant. Longitudinal decline was marked for all three groups. In a linear regression examining factors behind functional disability in CBS and PSP, memory dysfunction emerged as the main factor (48.5%), followed by apraxia (14.9%) and atypical parkinsonian symptoms (9.6%). CONCLUSIONS: Memory dysfunction is the most important factor in functional disability in CBS and PSP, which has to be taken into consideration in disease management, prognosis and planning of services to fully address patients' and families' needs.

Neural correlates of activities of daily living in frontotemporal dementia.

BACKGROUND: Little research to date has investigated neural correlates of functional disability in frontotemporal dementia (FTD). METHODS: Activities of daily living (ADL) were covaried against gray matter atrophy regions via Voxel-based morphometry in FTD (n = 52) and contrasted against a dementia control Alzheimer disease (AD) group (n = 20) and healthy age-matched controls (n = 18). RESULTS: Both patient groups had similar ADL scores. However, FTD and AD differed on the gray matter atrophy areas associated with ADL scores. The FTD showed involvement of prefrontal and thalamus regions while AD showed widespread temporal, parietal, frontal, and caudate atrophy correlating with ADL dysfunction. Importantly, only the left superior frontal gyrus was implicated in ADL dysfunction for both FTD and AD. CONCLUSIONS: Differences in underlying neural correlates of ADL impairment have important clinical implications as these differences should be taken into account when interventions are planned. Dementia subtypes might require specifically tailored interventions for functional disability.

Dissociation of explicit and implicit long-term memory consolidation in semantic dementia: a case study.

We report a case study of a semantic dementia patient, whose episodic memory consolidation was tested over a 2-month period. The results reveal that despite early retention of information, the patient lost all explicit information of the newly learnt material after 2 weeks. By contrast, he retained implicit word information even after a 4-week delay. These findings highlight the critical time window of 2-4 weeks in which newly learnt information should be re-encoded in rehabilitations studies. The results also indicate that learnt information can be still accessed with implicit retrieval strategies when explicit retrieval fails.

Longitudinal changes in primary progressive aphasias: differences in cognitive and dementia staging measures.

BACKGROUND/AIMS: The longitudinal course of three primary progressive aphasia (PPA) variants was examined using Addenbrooke's Cognitive Examination-Revised (ACE-R) and the Frontotemporal dementia Rating Scale (FRS). METHODS: Cases with two assessments on the ACE-R and FRS were selected. A total of 220 assessments were obtained on 55 patients: 17 Alzheimer's disease (AD) and 38 PPA [17 semantic variant (svPPA), 12 non-fluent/agrammatic (naPPA) and 9 logopenic variant (lvPPA) cases]. RESULTS: The annualized rate of change was greater in all PPA variants in comparison with the AD group on the ACE-R whereas only the svPPA and naPPA groups differed from AD on the FRS. CONCLUSIONS: The longitudinal profile differs across PPA syndromes on cognitive and functional measures. Findings have theoretical implications and are relevant to the care of patients with dementia.

Activities of daily living in progressive non-fluent aphasia, logopenic progressive aphasia and Alzheimer's disease.

BACKGROUND/AIMS: This study examined functional changes in progressive non-fluent aphasia (PNFA) and logopenic progressive aphasia (LPA) and Alzheimer's disease (AD) and the association between function, cognition and behaviour. METHODS: 59 patients were assessed with the Disability Assessment of Dementia (DAD), Addenbrooke's Cognitive Examination Revised (ACE-R) and the Cambridge Behavioural Inventory Revised (CBI-R). RESULTS: No differences between groups in basic and instrumental activities of daily living (ADLs), and total ACE-R scores were found; there were correlations between total DAD and ACE-R scores for PNFA and LPA. Over 12 months, PNFA showed the marked decline of basic ADLs, whereas all three groups showed marked decline of instrumental ADLs. CONCLUSION: PNFA, LPA and AD appear functionally similar when matched for disease duration. The rate of decline of ADLs depends, however, on disease diagnosis.

Activities of daily living in motor neuron disease: role of behavioural and motor changes.

Impairment in the activities of daily living (ADL) in motor neuron disease (MND) has been little investigated. The contributions of both behavioural and motor changes on functional performance have not been explored. A postal survey in New South Wales, Australia, included assessments of ADL, behavioural change (carer-based) and MND severity. Eighty-two patients were subdivided into groups according to onset presentation: bulbar (n=23) and limb (n=59). There were significant differences in ADL performance between limb and bulbar onset groups depending on ADL task. Disability was also dependent on disease severity as measured by the Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised (ALSFRS - R) score. Importantly, variance in ADL scores was dependent on both motor and behavioural factors. This study confirms the progressive disabling nature of MND, which is dependent on disease severity and shows qualitative differences depending on onset presentation. A model combining motor and behavioural changes explained 57% of variance on ADL performance, with important implications for clinical intervention.

Validation study of the Italian Addenbrooke's Cognitive Examination Revised in a young-old and old-old population.

AIMS: The main aims of the study were the translation and the subsequent validation in Italian of the Addenbrooke's Cognitive Examination Revised (ACE-R), and the evaluation of its usefulness in discriminating cognitively normal subjects from patients with mild dementia in an elderly population. METHODS: The ACE-R was translated and adapted into Italian. The Italian ACE-R was administered to a group of 179 elderly subjects (72 cognitively healthy and 107 subjects with mild dementia, mean age 75.4±6.4 years). The group was stratified into two subsamples according to age, i.e. a young-old (<75 years) and an old-old (≥75 years) group, in order to evaluate the sensitivity and specificity of the test in detecting dementia in different age strata of elderly subjects. RESULTS: The reliability of the Italian ACE-R was extremely good (α-coefficient=0.85). Two different cutoffs were identified for young-old (cutoff 79; sensitivity 90% and specificity 80%) and old-old subjects (cutoff 60; sensitivity 82% and specificity 100%). CONCLUSIONS: The Italian ACE-R is a valid screening tool to detect dementia, especially in the old-old population, which represents not only the fastest growing age group but also the group at the highest risk of dementia in Western countries.

Clinical staging and disease progression in frontotemporal dementia.

OBJECTIVE: We aimed to develop a novel tool capable of staging disease severity in frontotemporal dementia (FTD) based upon functional dependence and behavioral changes, and to assess change over time in the 3 main FTD variants (behavioral variant FTD [bvFTD]; progressive nonfluent aphasia [PNFA]; and semantic dementia [SemD]). METHODS: The Frontotemporal Dementia Rating Scale (FRS) was developed in a validation cohort of 77 consecutive clinic attendees (bvFTD = 29; PNFA = 20; SemD = 28) and applied to an independent sample of 75 patients (bvFTD = 28; PNFA = 21; SemD = 26) to establish intergroup differences. Assessments from 42 patients followed up after 12 months were used to determine annual progression. Finally, a combined sample (n = 152) was used to determine length of symptoms in each severity category. RESULTS: Six severity stages were identified and operationalized based upon a 30-item questionnaire (very mild to profound). The cross-sectional study revealed much greater levels of impairment in bvFTD than in the language variants, with limited correlation with general cognitive measures. Patients with SemD showed the closest association between length of symptoms and stage, taking, on average, 10 years to reach the severe stage. Patients with bvFTD appear to move most quickly between stages and patients with PNFA were intermediate. The FRS was capable of detecting functional deterioration in all 3 variants over 12 months. CONCLUSIONS: Disease progression differs across frontotemporal dementia (FTD) variants. Patients with behavioral variant FTD progress rapidly whereas those with semantic dementia progress more slowly. The Frontotemporal Dementia Rating Scale can aid in staging and determining disease progression. Length of symptoms and global cognitive assessments alone do not reflect disease severity and progression in FTD.

Orbitofrontal dysfunction discriminates behavioral variant frontotemporal dementia from Alzheimer's disease.

BACKGROUND: Behavioral variant frontotemporal dementia (bvFTD) patients show prefrontal cortex dysfunction and atrophy. METHODS: We investigated whether executive function in conjunction with prefrontal cortex atrophy discriminates bvFTD and Alzheimer's disease (AD) patients efficiently at presentation. RESULTS: AD and bvFTD patients were distinguishable by 89.5% on their performance of 3 executive tasks: the Hayling Test of Inhibitory Control, Digit Span Backward and Letter Fluency. Similarly, scan ratings showed that orbitofrontal cortex (OFC) and dorsolateral prefrontal cortex regions distinguish both patient groups. More importantly, employing the Hayling error score in conjunction with the OFC atrophy rating showed that 92% of patients can be correctly classified into bvFTD and AD. CONCLUSION: A combination of OFC and disinhibition measures appears to be a powerful diagnostic tool in differentiating bvFTD from AD patients in this preliminary study.