Everyday Memory Disturbance in Primary Progressive Aphasia.

INTRODUCTION: Mounting evidence indicates distinct memory profiles among the primary progressive aphasia (PPA) variants. Neuropsychological tests reveal disproportionate memory impairments in the logopenic variant PPA (lv-PPA) relative to the non-fluent variant PPA (nfv-PPA) and semantic variant PPA (sv-PPA). The real-world experience of day-to-day memory disturbances in PPA, however, remains poorly understood. METHODS: Everyday expressions of memory in 26 lv-PPA, 24 nfv-PPA, and 40 sv-PPA patients, and 70 healthy controls were examined using the Cambridge Behavioural Inventory-Revised (CBI-R) carer questionnaire. Kruskal-Wallis tests compared CBI-R Memory items (1-8) across groups. Receiver operating characteristic curves evaluated the most discriminative items to distinguish lv-PPA from nfv-PPA. RESULTS: Compared to controls, lv-PPA and sv-PPA patients were reported to experience more day-to-day memory issues (item 1), increased repetition of questions (2), forgetting the names of familiar people and objects (4, 5), and poor concentration (6). lv-PPA patients were also reported to exhibit more occurrences of losing or misplacing items (3) and forgetting the day (7). All PPA groups experienced more confusion in unfamiliar environments (8) than controls. Direct comparisons among PPA groups revealed distinct profiles, with lv-PPA and sv-PPA patients exhibiting more frequent forgetting of names and objects (3, 4) than nfv-PPA, and sv-PPA demonstrating greater day-to-day memory impairment (1), repeated questions (2), and poor concentration (6) compared to nfv-PPA. Forgetting the names of familiar objects (5) was the most sensitive and specific item to distinguish lv-PPA from nfv-PPA. CONCLUSIONS: Our findings demonstrate distinct day-to-day memory profiles in PPA. Future research should explore the influence of language impairments on these profiles.

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.

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.

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.

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.

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).

Characterisation of "Positive" Behaviours in Primary Progressive Aphasias.

BACKGROUND/AIMS: Although some patients with primary progressive aphasia (PPA) exhibit novel or improved skills after the onset of dementia, these changes have yet to be quantified. Therefore, this study systematically explored and identified the emergence of positive behaviours after dementia onset. METHODS: This study included 48 carers of patients with PPA: 12 nonfluent/agrammatic PPA (nfvPPA), 22 semantic variant PPA (svPPA), and 14 logopenic variant PPA (lvPPA). The presence and frequency of positive behaviour changes after dementia onset were established using the Hypersensory and Social/Emotional Scale (HSS). RESULTS: Scores on Sensitivity to Details, Visuospatial Activities, and Music Activities differed significantly among the groups. More specifically, svPPA was associated with increased visuospatial activity, but only in the mild stage of the disease; nfvPPA was associated with increased visuospatial activity and decreased music activity, while lvPPA exhibited the reverse profile. CONCLUSIONS: The results demonstrate that subsets of PPA patients show novel or increased positive behaviours following dementia onset, and differences among subtypes may be helpful for improving diagnostic accuracy. Additionally, harnessing these skills may improve the quality of life of both patients and carers.

Cognitive and Behavioral Symptoms in ALSFTD: Detection, Differentiation, and Progression.

Brief screening tools that detect and differentiate patients with amyotrophic lateral sclerosis and frontotemporal dementia (ALSFTD) from those more subtle cognitive or behavioral symptoms (ALS plus) and motor symptoms only (ALS pure) is pertinent in a clinical setting. The utility of 2 validated and data-driven tests (Mini-Addenbrooke's Cognitive Examination [M-ACE] and Motor Neuron Disease Behavioral Scale [MiND-B]) was investigated in 70 ALS patients (24 ALSFTD, 19 ALS plus, and 27 ALS pure). More than 90% of patients with ALSFTD scored at or below the cutoff on the M-ACE, whereas this was seen in only about 20% of ALS patients without dementia. The MiND-B differentiated between ALS pure and ALS plus diagnostic categories. Rasch modeling of M-ACE and MiND-B items revealed early cognitive (fluency, memory recall) and behavioral (apathy) symptoms in ALSFTD. The combined use of the M-ACE and MiND-B detects patients with ALSFTD, differentiates along the ALS continuum, and offers insight into the progression of nonmotor symptomatology in ALSFTD.

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.