Detecting clinical change with the CDR-FTLD:differences between FTLD and AD dementia

Objective: To investigate the psychometric properties of the Clinical Dementia Scale—frontotemporal lobar degeneration (CDR-FTLD) psychometric properties using Rasch analysis and its sensitivity distinguishing disease progression between FTLD and Alzheimer's disease (AD).  Methods: Of 603 consecutive patients from the National Alzheimer Coordinating Center dataset (FTLD = 350; AD = 253), 120 FTLDs were included in a Rasch analysis to verify CDR-FTLD psychometric properties; 483 (FTLD = 230; AD = 253) were included to analyse disease progression, with 195 (FTLD = 82; AD = 113) followed-up (24 months).  Results: The CDR-FTLD demonstrated good consistency, construct and concurrent validity and correlated well with mini-mental state examination (MMSE) and disease duration (ps < 0.05). At baseline, FTLD showed greater dementia severity than AD after matched for MMSE and disease duration (p < 0.001). Independent Rasch analyses demonstrated different patterns of progression for FTLD and AD in terms of the domains initially and then subsequently affected with disease progression. At follow-up, although MMSE showed significant changes (p < 0.05), these were greater on the CDR-FTLD (p < 0.001).  Conclusion: The CDR-FTLD satisfactorily measures dementia severity and change in FTLD, distinguishing disease progression between FTLD and AD, with clear implications for care, prognosis and future clinical trials. © 2016 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons, Ltd

Delusions in frontotemporal lobar degeneration

We assessed the significance and nature of delusions in frontotemporal lobar degeneration (FTLD), an important cause of young-onset dementia with prominent neuropsychiatric features that remain incompletely characterised. The case notes of all patients meeting diagnostic criteria for FTLD attending a tertiary level cognitive disorders clinic over a three year period were retrospectively reviewed and eight patients with a history of delusions were identified. All patients underwent detailed clinical and neuropsychological evaluation and brain MRI. The diagnosis was confirmed pathologically in two cases. The estimated prevalence of delusions was 14 %. Delusions were an early, prominent and persistent feature. They were phenomenologically diverse; however paranoid and somatic delusions were prominent. Behavioural variant FTLD was the most frequently associated clinical subtype and cerebral atrophy was bilateral or predominantly right-sided in most cases. We conclude that delusions may be a clinical issue in FTLD, and this should be explored further in future work

Altered sense of humor in dementia.

Sense of humor is potentially relevant to social functioning in dementias, but has been little studied in these diseases. We designed a semi-structured informant questionnaire to assess humor behavior and preferences in patients with behavioral variant frontotemporal dementia (bvFTD; n = 15), semantic dementia (SD; n = 7), progressive nonfluent aphasia (PNFA; n = 10), and Alzheimer's disease (AD; n = 16) versus healthy age-matched individuals (n = 21). Altered (including frankly inappropriate) humor responses were significantly more frequent in bvFTD and SD (all patients) than PNFA or AD (around 40% of patients). All patient groups liked satirical and absurdist comedy significantly less than did healthy controls. This pattern was reported premorbidly for satirical comedy in bvFTD, PNFA, and AD. Liking for slapstick comedy did not differ between groups. Altered sense of humor is particularly salient in bvFTD and SD, but also frequent in AD and PNFA. Humor may be a sensitive probe of social cognitive impairment in dementia, with diagnostic, biomarker and social implications

Longitudinal grey and white matter changes in frontotemporal dementia and Alzheimer's disease

Behavioural variant frontotemporal dementia (bvFTD) and Alzheimer's disease (AD) dementia are characterised by progressive brain atrophy. Longitudinal MRI volumetry may help to characterise ongoing structural degeneration and support the differential diagnosis of dementia subtypes. Automated, observer-independent atlas-based MRI volumetry was applied to analyse 102 MRI data sets from 15 bvFTD, 14 AD, and 10 healthy elderly control participants with consecutive scans over at least 12 months. Anatomically defined targets were chosen a priori as brain structures of interest. Groups were compared regarding volumes at clinic presentation and annual change rates. Baseline volumes, especially of grey matter compartments, were significantly reduced in bvFTD and AD patients. Grey matter volumes of the caudate and the gyrus rectus were significantly smaller in bvFTD than AD. The bvFTD group could be separated from AD on the basis of caudate volume with high accuracy (79% cases correct). Annual volume decline was markedly larger in bvFTD and AD than controls, predominantly in white matter of temporal structures. Decline in grey matter volume of the lateral orbitofrontal gyrus separated bvFTD from AD and controls. Automated longitudinal MRI volumetry discriminates bvFTD from AD. In particular, greater reduction of orbitofrontal grey matter and temporal white matter structures after 12 months is indicative of bvFTD

A comparison of magnetic resonance imaging and neuropsychological examination in the diagnostic distinction of Alzheimer’s disease and behavioral variant frontotemporal dementia

The clinical distinction between Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) remains challenging and largely dependent on the experience of the clinician. This study investigates whether objective machine learning algorithms using supportive neuroimaging and neuropsychological clinical features can aid the distinction between both diseases. Retrospective neuroimaging and neuropsychological data of 166 participants (54 AD; 55 bvFTD; 57 healthy controls) was analyzed via a Naïve Bayes classification model. A subgroup of patients (n = 22) had pathologically-confirmed diagnoses. Results show that a combination of gray matter atrophy and neuropsychological features allowed a correct classification of 61.47% of cases at clinical presentation. More importantly, there was a clear dissociation between imaging and neuropsychological features, with the latter having the greater diagnostic accuracy (respectively 51.38 vs. 62.39%). These findings indicate that, at presentation, machine learning classification of bvFTD and AD is mostly based on cognitive and not imaging features. This clearly highlights the urgent need to develop better biomarkers for both diseases, but also emphasizes the value of machine learning in determining the predictive diagnostic features in neurodegeneration

Estimating frontal and parietal involvement in cognitive estimation: a study of focal neurodegenerative diseases

We often estimate an unknown value based on available relevant information, a process known as cognitive estimation. In this study, we assess the cognitive and neuroanatomic basis for quantitative estimation by examining deficits in patients with focal neurodegenerative disease in frontal and parietal cortex. Executive function and number knowledge are key components in cognitive estimation. Prefrontal cortex has been implicated in multilevel reasoning and planning processes, and parietal cortex has been associated with number knowledge required for such estimations. We administered the Biber Cognitive Estimation Test (BCET) to assess cognitive estimation in 22 patients with prefrontal disease due to behavioral variant frontotemporal dementia (bvFTD), to 17 patients with parietal disease due to corticobasal syndrome (CBS) or posterior cortical atrophy (PCA) and 11 patients with mild cognitive impairment (MCI). Both bvFTD and CBS/PCA patients had significantly more difficulty with cognitive estimation than controls. MCI were not impaired on BCET relative to controls. Regression analyses related BCET performance to gray matter atrophy in right lateral prefrontal and orbital frontal cortices in bvFTD, and to atrophy in right inferior parietal cortex, right insula and fusiform cortices in CBS/PCA. These results are consistent with the hypothesis that a frontal-parietal network plays a crucial role in cognitive estimation

Detección de displasias corticales asistida mediante métodos semiautomáticos de espesor cortical

 Objetivo: Evaluar la detección de displasias corticales utilizando un método semiautomá- tico de cuantificación morfométrica basado en superficie mediante la localización de zonas con espesor cortical anormal. Materiales y métodos: Se seleccionó un grupo de pacientes remitidos por diagnóstico de epilepsia refractaria para la detección de lesiones cerebrales. El espesor cortical se midió utilizando algoritmos automáticos de morfometría basado en superficie de imágenes de resonancia magnética en cada uno de los pacientes, los cuales fueron comparados con un grupo control de sujetos sanos pareados por edad. Resultados: Se realizó la cuantificación de espesor cortical en 4 de los 5 pacientes selec- cionados. Se encontraron áreas de engrosamiento cortical en las zonas de displasia cortical conocidas que se relacionaron con las zonas detectadas previamente por el radiólogo en la secuencia FLAIR de cada paciente. Se hallaron diferencias en los mapas de espesor cortical de cada paciente respecto al grupo control. Conclusión: La cuantificación morfométrica de espesor cortical es una técnica que promete ser de utilidad como asistencia computarizada al diagnóstico de las displasias corticales

Comparison of prefrontal atrophy and episodic memory performance in dysexecutive Alzheimer’s disease and behavioural-variant frontotemporal dementia

Alzheimer’s disease (AD) sometimes presents with prominent executive dysfunction and associated prefrontal cortex atrophy. The impact of such executive deficits on episodic memory performance as well as their neural correlates in AD, however, remains unclear. The aim of the current study was to investigate episodic memory and brain atrophy in AD patients with relatively spared executive functioning (SEF-AD; n = 12) and AD patients with relatively impaired executive functioning (IEF-AD; n = 23). We also compared the AD subgroups with a group of behavioral-variant frontotemporal dementia patients (bvFTD; n = 22), who typically exhibit significant executive deficits, and age-matched healthy controls (n = 38). On cognitive testing, the three patient groups showed comparable memory profiles on standard episodic memory tests, with significant impairment relative to controls. Voxel-based morphometry analyses revealed extensive prefrontal and medial temporal lobe atrophy in IEF-AD and bvFTD, whereas this was limited to the middle frontal gyrus and hippocampus in SEF-AD. Moreover, the additional prefrontal atrophy in IEF-AD and bvFTD correlated with memory performance, whereas this was not the case for SEF-AD. These findings indicate that IEF-AD patients show prefrontal atrophy in regions similar to bvFTD, and suggest that this contributes to episodic memory performance. This has implications for the differential diagnosis of bvFTD and subtypes of AD

Prospective memory impairments in Alzheimer's Disease and behavioral variant frontotemporal dementia: Clinical and neural correlates

BACKGROUND: Prospective memory (PM) refers to a future-oriented form of memory in which the individual must remember to execute an intended action either at a future point in time (Time-based) or in response to a specific event (Event-based). Lapses in PM are commonly exhibited in neurodegenerative disorders including Alzheimer's disease (AD) and frontotemporal dementia (FTD), however, the neurocognitive mechanisms driving these deficits remain unknown. OBJECTIVE: To investigate the clinical and neural correlates of Time- and Event-based PM disruption in AD and the behavioral-variant FTD (bvFTD). METHODS: Twelve AD, 12 bvFTD, and 12 healthy older Control participants completed a modified version of the Cambridge Prospective Memory test, which examines Time- and Event-based aspects of PM. All participants completed a standard neuropsychological assessment and underwent whole-brain structural MRI. RESULTS: AD and bvFTD patients displayed striking impairments across Time- and Event-based PM relative to Controls, however, Time-based PM was disproportionately affected in the AD group. Episodic memory dysfunction and hippocampal atrophy was found to correlate strongly with PM integrity in both patient groups, however, dissociable neural substrates were also evident for PM performance across dementia syndromes. CONCLUSION: Our study reveals the multifaceted nature of PM dysfunction in neurodegenerative disorders, and suggests common and dissociable neurocognitive mechanisms, which subtend these deficits in each patient group. Future studies of PM disturbance in dementia syndromes will be crucial for the development of successful interventions to improve functional independence in the patient's daily life

Lost in spatial translation - A novel tool to objectively assess spatial disorientation in Alzheimer's disease and frontotemporal dementia

Spatial disorientation is a prominent feature of early Alzheimer's disease (AD) attributed to degeneration of medial temporal and parietal brain regions, including the retrosplenial cortex (RSC). By contrast, frontotemporal dementia (FTD) syndromes show generally intact spatial orientation at presentation. However, currently no clinical tasks are routinely administered to objectively assess spatial orientation in these neurodegenerative conditions. In this study we investigated spatial orientation in 58 dementia patients and 23 healthy controls using a novel virtual supermarket task as well as voxel-based morphometry (VBM). We compared performance on this task with visual and verbal memory function, which has traditionally been used to discriminate between AD and FTD. Participants viewed a series of videos from a first person perspective travelling through a virtual supermarket and were required to maintain orientation to a starting location. Analyses revealed significantly impaired spatial orientation in AD, compared to FTD patient groups. Spatial orientation performance was found to discriminate AD and FTD patient groups to a very high degree at presentation. More importantly, integrity of the RSC was identified as a key neural correlate of orientation performance. These findings confirm the notion that i) it is feasible to assess spatial orientation objectively via our novel Supermarket task; ii) impaired orientation is a prominent feature that can be applied clinically to discriminate between AD and FTD and iii) the RSC emerges as a critical biomarker to assess spatial orientation deficits in these neurodegenerative conditions