Visuospatial working memory in behavioural variant frontotemporal dementia: a comparative analysis with Alzheimer's disease using the box task.

OBJECTIVE: This study investigated the visuospatial working memory profiles of behavioural variant frontotemporal dementia (bvFTD) and Alzheimer's disease (AD) using a novel computerised test of visuospatial working memory: the Box Task. METHODS: Twenty-eight bvFTD and 28 AD patients, as well as 32 age-matched control participants were recruited. All participants completed the Box Task and conventional neuropsychological tests of working memory, episodic memory, and visuospatial function. RESULTS: Both the bvFTD and AD groups exhibited significantly more Box Task between-search errors than the control group across all set sizes. Notably, the AD group demonstrated a significantly higher error rate compared to the bvFTD group. Regression analysis revealed that whilst episodic memory impairment significantly predicted Box Task error performance in AD, this was not the case for bvFTD. Additionally, a noticeable trend was observed for attention in predicting Box Task errors in both bvFTD and AD groups. The Box Task demonstrated high utility in differentiating between bvFTD and AD, with a decision tree correctly classifying 82.1% of bvFTD patients and 75% of AD patients. CONCLUSIONS: Our findings reveal significant visuospatial working memory impairments in bvFTD, albeit of lesser severity compared to disease-matched AD patients. The Box Task, a novel measure of visuospatial working memory, proved effective in differentiating between bvFTD and AD, outperforming many traditional neuropsychological measures. Overall, our findings highlight the utility of assessing visuospatial memory when differentiating between bvFTD and AD in the clinical setting.

Dementia in Australia: Clinical recommendations post-diagnosis.

The delivery of a dementia diagnosis, the information provided, and the practical advice and support arranged can have a long-lasting impact on patients and their families and deserves attention equal to that given to the assessment and investigation process. Patients and their families need a constructive yet sensitive conversation about the nature and cause of their difficulties, communicated in plain language, and tailored to their main concerns and needs. This conversation should lead to the provision of high-quality, easily accessible information. Following this, clinicians may wish to consider broaching the following dementia topics: (1) pharmacological and non-pharmacological interventions, (2) connection and integration with relevant organisations, (3, 4) application for formal support services and engagement with support teams, (5) safety in the home, (6, 7) financial planning, guardianship and legal matters, (8) driving eligibility, (9) support and education resources to family carers and (10) research initiatives and genetic information. Addressing these topics will contribute to improved disease management, which is likely to improve the dementia journey for the patient, their carer(s), and family.

Frequency of cognitive "super-aging" in three Australian samples using different diagnostic criteria.

OBJECTIVES: To investigate the frequency of exceptional cognition (cognitive super-aging) in Australian older adults using different published definitions, agreement between definitions, and the relationship of super-aging status with function, brain imaging markers, and incident dementia. DESIGN: Three longitudinal cohort studies. SETTING: Participants recruited from the electoral roll, Australian Twins Registry, and community advertisements. PARTICIPANTS: Older adults (aged 65-106) without dementia from the Sydney Memory and Ageing Study (n = 1037; median age 78), Older Australian Twins Study (n = 361; median age 68), and Sydney Centenarian Study (n = 217; median age 97). MEASUREMENTS: Frequency of super-aging was assessed using nine super-aging definitions based on performance on neuropsychological testing. Levels of agreement between definitions were calculated, and associations between super-aging status for each definition and functioning (Bayer ADL score), structural brain imaging measures, and incident dementia were explored. RESULTS: Frequency of super-aging varied between 2.9 and 43.4 percent with more stringent definitions associated with lower frequency. Agreement between different criteria varied from poor (K = 0.04, AC1 = .24) to very good (K = 0.83, AC1 = .91) with better agreement between definitions using similar tests and cutoffs. Super-aging was associated with better functional performance (4.7-11%) and lower rates of incident dementia (hazard ratios 0.08-0.48) for most definitions. Super-aging status was associated with a lower burden of white matter hyperintensities (3.8-33.2%) for all definitions. CONCLUSIONS: The frequency of super-aging is strongly affected by the demographic and neuropsychological testing parameters used. Greater consistency in defining super-aging would enable better characterization of this exceptional minority.

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.

Olfactory Bulb Integrity in Frontotemporal Dementia and Alzheimer's Disease.

BACKGROUND: Olfactory dysfunction is highly prevalent in dementia syndromes, including Alzheimer's disease (AD) and frontotemporal dementia (FTD). The structural integrity of the olfactory bulb (OB) is thought to play a critical role in odor detection and identification, but no MRI study has measured OB volume in FTD, or measured OB volume longitudinally in AD. OBJECTIVE: To measure OB volume in FTD and AD patients longitudinally using MRI. METHODS: This study measured OB volumes using MRI in patients diagnosed with behavioral-variant FTD (n = 55), semantic dementia (n = 34), progressive non-fluent aphasia (n = 30), AD (n = 50), and healthy age-matched controls (n = 55) at their first visit to a dementia research clinic ('baseline'). Imaging data in patients 12-months later were analyzed where available (n = 84) for longitudinal assessment. Volumes of subcortical and cortical olfactory regions ('olfactory network') were obtained via surface-based morphometry. RESULTS: Results revealed that in AD and FTD at baseline, OB volumes were similar to controls, whereas volumes of olfactory network regions were significantly reduced in all patient groups except in progressive non-fluent aphasia. Longitudinal data revealed that OB volume became significantly reduced (10-25% volume reduction) in all dementia groups with disease progression. CONCLUSION: Olfactory dysfunction is common in patients diagnosed with AD or FTD, but our results indicate that there is no detectable volume loss to the OBs upon first presentation to the clinic. Our findings indicate that the OBs become detectably atrophied later in the disease process. OB atrophy indicates the potential usefulness for OBs to be targeted in interventions to improve olfactory function.

Longitudinal changes in behaviour, mood and functional capacity in the primary progressive aphasia variants.

Primary progressive aphasia (PPA) is a neurodegenerative clinical syndrome characterised by a progressive decline in speech and language functions. Deficits in behaviour, mood and functional capacity are reported in PPA but are less well understood. This study examined the PPA variants' profiles on these domains at initial presentation and over time and evaluated their relations to overall cognitive ability. Behaviour, mood and functional capacity were measured annually (over ~6 years) in 145 individuals diagnosed with PPA (41 logopenic [lv-PPA], 44 non-fluent [nfv-PPA] and 60 semantic variants [sv-PPA]) using the Cambridge Behavioural Inventory-Revised (CBI-R) carer questionnaire. Overall cognition was assessed annually with the Addenbrooke's Cognitive Examination-III. Distinct profiles were observed across PPA syndromes. Notably, sv-PPA carers reported greater behavioural, eating and motivational disturbances than the other PPA variants throughout the disease course. Reported memory problems were also greater in sv-PPA and lv-PPA than in nfv-PPA across all time points. These disturbances occurred in the context of the sv-PPA group demonstrating a slower rate of cognitive decline than the lv-PPA group and a parallel rate to that found in the nfv-PPA group. Associations between overall cognition and the CBI-R domains were trivial at baseline assessment; however, distinct profiles emerged when mapping each syndrome's overall cognitive decline with their behavioural, mood and functional trajectories. Our findings demonstrate that the evolving behaviour, mood and functional capacity profiles of the PPA variants are distinct and extend beyond the primary disorder of language. These findings have important implications for clinical management and caregiver education in PPA.

Cognitive and Neural Mechanisms of Social Communication Dysfunction in Primary Progressive Aphasia.

Mounting evidence suggests that, in parallel with well-defined changes in language, primary progressive aphasia (PPA) syndromes display co-occurring social cognitive impairments. Here, we explored multidimensional profiles of carer-rated social communication using the La Trobe Communication Questionnaire (LCQ) in 11 semantic dementia (SD), 12 logopenic progressive aphasia (LPA) and 9 progressive non-fluent aphasia (PNFA) cases and contrasted their performance with 19 Alzheimer's disease (AD) cases, 26 behavioural variant frontotemporal dementia (bvFTD) cases and 31 healthy older controls. Relative to the controls, the majority of patient groups displayed significant overall social communication difficulties, with common and unique profiles of impairment evident on the LCQ subscales. Correlation analyses revealed a differential impact of social communication disturbances on functional outcomes in patient and carer well-being, most pronounced for SD and bvFTD. Finally, voxel-based morphometry analyses based on a structural brain MRI pointed to the degradation of a distributed brain network in mediating social communication dysfunction in dementia. Our findings suggest that social communication difficulties are an important feature of PPA, with significant implications for patient function and carer well-being. The origins of these changes are likely to be multifactorial, reflecting the breakdown of fronto-thalamic brain circuits specialised in the integration of complex information.

Evidence for a pervasive autobiographical memory impairment in Logopenic Progressive Aphasia.

Although characterized primarily as a language disorder, mounting evidence indicates episodic amnesia in Logopenic Progressive Aphasia (LPA). Whether such memory disturbances extend to information encoded pre-disease onset remains unclear. To address this question, we examined autobiographical memory in 10 LPA patients, contrasted with 18 typical amnestic Alzheimer's disease and 16 healthy Control participants. A validated assessment, the Autobiographical Interview, was employed to explore autobiographical memory performance across the lifespan under free and probed recall conditions. Relative to Controls, LPA patients showed global impairments across all time periods for free recall, scoring at the same level as disease-matched cases of Alzheimer's disease. Importantly, these retrieval deficits persisted in LPA, even when structured probing was provided, and could not be explained by overall level of language disruption or amount of information generated during autobiographical narration. Autobiographical memory impairments in LPA related to gray matter intensity decrease in predominantly posterior parietal brain regions implicated in memory retrieval. Together, our results suggest that episodic memory disturbances may be an under-appreciated clinical feature of LPA.

Verbal Short-Term Memory Disturbance in the Primary Progressive Aphasias: Challenges and Distinctions in a Clinical Setting.

Impaired verbal 'phonological' short-term memory is considered a cardinal feature of the logopenic variant of primary progressive aphasia (lv-PPA) and is assumed to underpin most of the language deficits in this syndrome. Clinically, examination of verbal short-term memory in individuals presenting with PPA is common practice and serves two objectives: (i) to help understand the possible mechanisms underlying the patient's language profile and (ii) to help differentiate lv-PPA from other PPA variants or from other dementia syndromes. Distinction between lv-PPA and the non-fluent variant of PPA (nfv-PPA), however, can be especially challenging due to overlapping language profiles and comparable psychometric performances on verbal short-term memory tests. Here, we present case vignettes of the three PPA variants (lv-PPA, nfv-PPA, and the semantic variant (sv-PPA)) and typical Alzheimer's disease (AD). These vignettes provide a detailed description of the short-term and working memory profiles typically found in these patients and highlight how speech output and language comprehension deficits across the PPA variants differentially interfere with verbal memory performance. We demonstrate that a combination of verbal short-term and working memory measures provides crucial information regarding the cognitive mechanisms underlying language disturbances in PPA. In addition, we propose that analogous visuospatial span tasks are essential for the assessment of PPA as they measure memory capacity without language contamination.

The Box Task: A novel tool to differentiate the primary progressive aphasias.

OBJECTIVE: Differentiating the primary progressive aphasia (PPA) variants in clinical settings remains complex and challenging, especially for the logopenic (lv-PPA) and non-fluent 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.

Heterogeneity of behavioural and language deficits in FTD-MND.

OBJECTIVE: To comprehensively examine the clinical presentation of patients diagnosed with frontotemporal dementia-motor neuron disease (FTD-MND) compared to FTD subtypes. To clarify the heterogeneity of behavioural and language deficits in FTD-MND using a data-driven approach. METHODS: Patients with FTD-MND (n = 31), behavioural variant FTD (n = 119), non-fluent variant primary progressive aphasia (n = 47), semantic variant primary progressive aphasia (n = 42), and controls (n = 127) underwent comprehensive clinical, cognitive and behavioural assessments. Two-step cluster analysis examined patterns of behavioural and language impairment. Voxel-based morphometry and tract-based spatial statistics were used to investigate differences across the subgroups that emerged from cluster analysis. RESULTS: More than half of FTD-MND patients initially presented with variable combinations of deficits (e.g., mixed behaviour/cognitive, mixed behaviour/cognitive/motor deficits), with 74% of them meeting criteria for FTD-MND within 24 months with a median of 12 months. The frequency and severity of behavioural and language abnormalities in FTD-MND lie between that seen in the three FTD phenotypes. Cluster analysis identified three patterns of behavioural and language impairment in FTD-MND. The three FTD-MND subgroups demonstrated different profiles of white matter tract disruption, but did not differ in age at onset, disease duration or patterns of cortical atrophy. CONCLUSIONS: While highly heterogeneous, in terms of behavioural and language deficits, and disease severity, the presentation of FTD-MND may be distinct to that of FTD. Distinct white matter degeneration patterns may underpin heterogeneous clinical profiles in FTD-MND. FTD presenting with mixed behavioural-language disturbances should be monitored closely for at least 12-24 months for the emergence of MND symptoms/signs.

Longitudinal cognitive and functional changes in primary progressive aphasia.

OBJECTIVE: The variants of primary progressive aphasia (PPA) are predominantly diagnosed on the basis of specific profiles of language impairments. Deficits in other cognitive domains and their evolution over time are less well documented. This study examined the cognitive profiles of the PPA variants over time and determined the contribution of cognition on functional capacity. METHODS: Longitudinal performance on the Addenbrooke's Cognitive Examination-III (ACE-III) total and cognitive subdomains were investigated in 147 PPA individuals (41 logopenic [lv-PPA], 44 non-fluent [nfv-PPA], and 62 semantic variants [sv-PPA]). The relative contribution of ACE-III subdomain scores to overall functional capacity over time was identified using mixed and hierarchical regression modelling. RESULTS: The annual rate of global ACE-III decline was twice that in lv-PPA than in nfv-PPA and sv-PPA, despite lv-PPA performing intermediate to the other variants at baseline assessment. Notably, attention and visuospatial subdomains declined faster in lv-PPA than in nfv-PPA and sv-PPA; and memory impairment was more severe in lv-PPA than in nfv-PPA at all time points. Functional decline was comparable across PPA variants; however, the contribution of cognition on functional capacity varied across variants and over time. CONCLUSION: The cognitive profiles of the PPA variants are distinct at baseline and over time. Crucially, cognitive decline in lv-PPA was more widespread and pervasive than in nfv-PPA and sv-PPA. Our findings also demonstrate the complex interplay between cognition and functional capacity. This study underscores the importance of routinely assessing cognition and functional capacity in PPA to improve diagnostic accuracy and provide targeted support services.

Problem-focused coping underlying lower caregiver burden in ALS-FTD: implications for caregiver intervention.

Objective: Amyotrophic lateral sclerosis (ALS) is a multisystem neurodegenerative disorder which includes cognitive and behavioral symptoms akin to frontotemporal dementia (FTD). Despite the necessity of caregiver intervention to assist with the management of cognitive and behavioral 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 behavioral symptoms. Methods: Fifty-five patient-caregiver dyads were recruited from specialized 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 analyzed 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 optimizing problem-focused coping strategies as part of multidisciplinary ALS care, particularly for caregivers of ALS-FTD patients may mitigate caregiver burden.

Visuospatial short-term and working memory disturbance in the primary progressive aphasias: Neuroanatomical and clinical implications.

INTRODUCTION: Primary progressive aphasia (PPA) comprises three main variants: logopenic (lv-PPA), non-fluent (nfv-PPA) and semantic variant (sv-PPA). Differentiating the language profiles of the PPA variants remains challenging, especially for lv-PPA and nfv-PPA. As such, diagnostic tools that do not rely on speech and language may offer some utility. Here, we investigated the short-term and working memory profiles of the PPA variants and typical Alzheimer's disease (AD), with a particular interest in the visuospatial system. We hypothesised visuospatial short-term and working memory would be more compromised in lv-PPA and AD than in the other PPA variants, and that this would relate to degeneration of posterior temporoparietal brain regions. METHOD: Thirty-three lv-PPA, 26 nfv-PPA, 31 sv-PPA and 58 AD patients, and 45 matched healthy controls were recruited. All participants completed the WMS-III Spatial and Digit Span tasks and underwent a structural brain MRI for voxel-based morphometry analyses. RESULTS: Relative to Controls, Spatial Span Forward (SSF) performance was impaired in lv-PPA and AD but not in nfv-PPA or sv-PPA. In contrast, Digit Span Forward (DSF) performance was impaired in lv-PPA and nfv-PPA (to a similar level), and AD, but was relatively intact in sv-PPA. As expected, most backward span scores across both modalities were lower than forward span scores. Neuroimaging analyses revealed that SSF and SSB performance in all patients combined correlated with grey matter intensity decrease in several clusters located in temporo-parieto-occipital brain regions. Post-hoc group comparisons of these regions showed that grey matter loss was more extensive in the lv-PPA and AD groups than in the nfv-PPA and sv-PPA groups. CONCLUSIONS: The findings suggest that the visuospatial short-term and working memory profiles of the PPA variants are separable and likely reflect their distinct patterns of temporo-parieto-occipital brain atrophy.

What to make of equivocal amyloid imaging results.

INTRODUCTION: Six patients with equivocal amyloid-PET results are discussed. METHODS: Patients underwent clinical/neuropsychological assessment, MRI, and amyloid-PET. Equivocal amyloid-PET was defined as cortical ligand binding with SUVR < 1.40. Follow-up for up to 5 years is presented. RESULTS: 6 patients (4 males, 2 females, mean age 71.8 +/- 2.5 years) with equivocal amyloid-PET were included from 136 patients who underwent amyloid-PET (4.4% of cases). Patients had variable language, behavioral, and cognitive deficits. Progression varied from no deterioration to residential care within 3 years. DISCUSSION: Equivocal amyloid-PET should be interpreted cautiously. Improved biomarkers of AD and other neurodegenerative diseases are needed.

Visuospatial dysfunction in Alzheimer's disease and behavioural variant frontotemporal dementia.

OBJECTIVES: Approximately 30% of Alzheimer's disease (AD) patients are misdiagnosed due to overlapping and evolving clinical features. In particular, the distinction of AD from behavioural variant frontotemporal dementia (bvFTD) can be challenging. Measures of visuospatial ability, which rely on parietal lobe function, show promise as markers of AD as the parietal lobe is preferentially affected early in the disease course. We hypothesise that traditional measures of visuospatial function may help distinguish AD from bvFTD. MATERIALS & METHODS: The Addenbrooke's Cognitive Examination (ACE) visuospatial subtask, Rey-Osterrieth Complex Figure (RCF) task, and subtests of the visual object and space perception battery (VOSP) were used to examine visuospatial abilities in 55 AD patients, 51 bvFTD patients, and 54 healthy Controls. A subgroup analysis was performed in patients with Pittsburgh Compound B positron emission tomography (PiB-PET) data. RESULTS: Relative to Controls, AD and bvFTD patients were impaired on almost all visuospatial tasks. Significantly worse performance was observed in AD relative to bvFTD patients on drawing tasks (ACE pentagons/loops copy, cube copy, and all RCF scores) and tasks of spatial orientation (VOSP cube analysis), when controlling for disease severity. CONCLUSIONS: Visuospatial measures demonstrate limited ability to distinguish between AD and bvFTD unless disease severity is taken into consideration. Controlling for disease severity reveals a disproportionate visuospatial impairment in AD compared to bvFTD. Development of targeted measures of visuospatial function is required to improve differential diagnosis of these syndromes.

Sustained attention failures on a 3-min reaction time task is a sensitive marker of dementia.

The objective of the study is to determine the utility of a simple reaction time task as a marker of general cognitive decline across the frontotemporal lobar degeneration (FTLD) spectrum and in Alzheimer's disease (AD). One hundred and twelve patients presenting with AD or FTLD affecting behaviour (behavioural-variant frontotemporal dementia), language (progressive non fluent aphasia, logopenic progressive aphasia, semantic dementia) or motor function (corticobasal syndrome, progressive supranuclear palsy, frontotemporal dementia-motor neuron disease) and 25 age-matched healthy controls completed the Psychomotor Vigilance Task (PVT), a 3-min reaction time (RT) task. The proportion of lapses (RT > 500 ms) was significantly increased in dementia patients compared to healthy controls, except for semantic dementia, and correlated with all cognitive functions except language. Discrimination of individuals (dementia patients versus healthy controls) based on the proportion of lapses yielded the highest classification performance (Area Under the Curve, AUC, 0.90) compared to standard neuropsychological tests. Only the complete and lengthy neuropsychological battery had a higher predictive value (AUC 0.96). The basic ability to sustain attention is fundamental to perform any cognitive task. Lapses, interpreted as momentary shifts in goal-directed processing, can therefore, be used as a marker of general cognitive decline indicative of possible dementia.

Lexical retrieval treatment in primary progressive aphasia: An investigation of treatment duration in a heterogeneous case series.

Word-finding difficulty is typically an early and frustrating symptom of primary progressive aphasia (PPA), prompting investigations of lexical retrieval treatment in PPA. This study aimed to investigate immediate treatment gains following two versus four weeks of treatment, item generalisation, and maintenance of gains with ongoing treatment in a single case series of eight individuals with heterogeneous PPA presentations (three non-fluent/agrammatic, two logopenic, two semantic, and one mixed PPA). Three individuals made initial gains in picture naming and maintained them over 6 months or more with ongoing treatment. By contrast, three individuals made marginal initial gains but were unable to continue treatment, and two individuals did not make the typically-reported initial gains with two or four weeks of treatment. There was little evidence of generalisation to untreated items. Our results add to the evidence that daily home practice of Repetition and Reading in the Presence of a Picture over extended periods can increase and maintain retrieval of personally-relevant words in picture naming for some individuals with semantic or nonfluent/agrammatic variant PPA. Further research is needed into the factors associated with long-term treatment adherence and gains, and the factors associated with nonadherence to treatment.

Intrafamilial Phenotypic Variability in the C9orf72 Gene Expansion: 2 Case Studies.

The C9orf72 genetic mutation is the most common cause of familial frontotemporal dementia (FTD) and motor neuron disease (MND). Previous family studies suggest that while some common clinical features may distinguish gene carriers from sporadic patients, the clinical features, age of onset and disease progression vary considerably in affected patients. Whilst disease presentations may vary across families, age at disease onset appears to be relatively uniform within each family. Here, we report two individuals with a C9orf72 repeat expansion from two generations of the same family with markedly different age at disease onset, clinical presentation and disease progression: one who developed motor neuron and behavioural symptoms in their mid 40s and died 3 years later with confirmed TDP-43 pathology and MND; and a second who developed cognitive and mild behavioural symptoms in their mid 70s and 8 years later remains alive with only slow deterioration. This report highlights the phenotypic variability, including age of onset, within a family with the C9orf72 repeat expansion.

Addenbrooke's Cognitive Examination III: Psychometric Characteristics and Relations to Functional Ability in Dementia.

OBJECTIVES: The Addenbrooke's Cognitive Examination (ACE) is a common cognitive screening test for dementia. Here, we examined the relationship between the most recent version (ACE-III) and its predecessor (ACE-R), determined ACE-III cutoff scores for the detection of dementia, and explored its relationship with functional ability. METHODS: Study 1 included 199 dementia patients and 52 healthy controls who completed the ACE-III and ACE-R. ACE-III total and domain scores were regressed on their corresponding ACE-R values to obtain conversion formulae. Study 2 included 331 mixed dementia patients and 87 controls to establish the optimal ACE-III cutoff scores for the detection of dementia using receiver operator curve analysis. Study 3 included 194 dementia patients and their carers to investigate the relationship between ACE-III total score and functional ability. RESULTS: Study 1: ACE-III and ACE-R scores differed by ≤1 point overall, the magnitude varying according to dementia type. Study 2: a new lower bound cutoff ACE-III score of 84/100 to detect dementia was identified (compared with 82 for the ACE-R). The upper bound cutoff score of 88/100 was retained. Study 3: ACE-III scores were significantly related to functional ability on the Clinical Dementia Rating Scale across all dementia syndromes, except for semantic dementia. CONCLUSIONS: This study represents one of the largest and most clinically diverse investigations of the ACE-III. Our results demonstrate that the ACE-III is an acceptable alternative to the ACE-R. In addition, ACE-III performance has broader clinical implications in that it relates to carer reports of functional impairment in most common dementias. (JINS, 2018, 24, 854-863).