The Mini-Addenbrooke's Cognitive Examination: a new assessment tool for dementia.

BACKGROUND/AIMS: We developed and validated the Mini-Addenbrooke's Cognitive Examination (M-ACE) in dementia patients. Comparisons were also made with the Mini Mental State Examination (MMSE). METHOD: The M-ACE was developed using Mokken scaling analysis in 117 dementia patients [behavioural variant frontotemporal dementia (bvFTD), n = 25; primary progressive aphasia (PPA), n = 49; Alzheimer's disease (AD), n = 34; corticobasal syndrome (CBS), n = 9] and validated in an independent sample of 164 dementia patients (bvFTD, n = 23; PPA, n = 82; AD, n = 38; CBS, n = 21) and 78 controls, who also completed the MMSE. RESULTS: The M-ACE consists of 5 items with a maximum score of 30. Two cut-offs were identified: (1) ≤25/30 has both high sensitivity and specificity, and (2) ≤21/30 is almost certainly a score to have come from a dementia patient regardless of the clinical setting. The M-ACE is more sensitive than the MMSE and is less likely to have ceiling effects. CONCLUSION: The M-ACE is a brief and sensitive cognitive screening tool for dementia. Two cut-offs (25 or 21) are recommended.This work was supported by funding to Forefront, a collaborative research group dedicated to the study of frontotemporal dementia and motor neurone disease, by the National Health and Medical Research council (NHMRC) of Australia program grant (1037746) and the Australian Research Council (ARC) Centre of Excellence in Cognition and Its Disorders Memory Node (CE110001021). S.H. is supported by the Graham Linford Fellowship from the Motor Neurone Disease Research Institute of Australia. S.M. is supported by Alzheimer Scotland (PhD Studentship). F.L. is supported by an Australian Postgraduate Award (PhD Scholarship). K.D. is supported by NIHR Cambridge Biomedical Research Centre. S.A. is supported by the NIHR Biomedical Research Centre, Oxford. C.R.B. is supported by a Clinician Scientist Fellowship from the Medical Research Council (MR/K010395/1). J.B.R. is supported by the Wellcome Trust (088324), Medical Research Council, McDonnell Foundation and the NIHR (Cambridge Biomedical Research Centre and Biomedical Research Unit in Dementia). E.M. is supported by the NHMRC Early Career Fellowship (1016399) and Alzheimer Association USA. J.R.H. is supported by an ARC Federation Fellowship (FF0776229).This is the final version of the article. It first appeared from Karger via http://dx.doi.org/10.1159/00036604

Behavioral-variant frontotemporal dementia: Distinct phenotypes with unique functional profiles

Objective: To identify distinct behavioral phenotypes of behavioral variant frontotemporal dementia (bvFTD), and elucidate differences in functional, neuroimaging, and progression to residential care placement. Methods: Eighty-eight patients with bvFTD were included in a cluster analysis applying levels of disinhibition and apathy (Cambridge Behavioural Inventory-Revised) to identify phenotypic subgroups. Between-group (Kruskal-Wallis; Mann-Whitney U) functional differences (Disability Assessment for Dementia), and time to residential care placement (survival analyses) were examined. Cortical thickness differences (whole brain MRI) were analyzed in bvFTD patients versus healthy controls (n=30) and between phenotypic subgroups. Results: Four phenotypic subgroups were identified: “Primary severe apathy” (n=26), “Severe apathy and disinhibition” (n=26), “Mild apathy and disinhibition” (n=27), “Primary severe disinhibition” (n= 9). Severely apathetic phenotypes were more functionally impaired and had more extensive brain atrophy than those with mild apathy or severe disinhibition alone. Further imaging analyses indicated that the right middle temporal region is critical for the development of disinhibition, an association that remains with disease progression and in the context of severe apathy. Finally, no difference in time to residential care admission was found between phenotypes. Conclusions: This study reveals that different clinical behavioral phenotypes of bvFTD have differing profiles of functional decline and distinct patterns of associated cortical changes. These findings emphasize the importance of apathy in functional impairment, highlight the role of the right temporal region in disinhibition and suggest that disability may be a sensitive outcome measure for treatments targeting reduction of apathy. These phenotypes could also support understanding of prognosis and clinical management

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 clini- cally 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

Grey and white matter correlates of recent and remote autobiographical memory retrieval:Insights from the dementias

The capacity to remember self-referential past events relies on the integrity of a distributed neural network. Controversy exists, however, regarding the involvement of specific brain structures for the retrieval of recently experienced versus more distant events. Here, we explored how characteristic patterns of atrophy in neurodegenerative disorders differentially disrupt remote versus recent autobiographical memory. Eleven behavioural-variant frontotemporal dementia, 10 semantic dementia, 15 Alzheimer's disease patients and 14 healthy older Controls completed the Autobiographical Interview. All patient groups displayed significant remote memory impairments relative to Controls. Similarly, recent period retrieval was significantly compromised in behavioural-variant frontotemporal dementia and Alzheimer's disease, yet semantic dementia patients scored in line with Controls. Voxel-based morphometry and diffusion tensor imaging analyses, for all participants combined, were conducted to investigate grey and white matter correlates of remote and recent autobiographical memory retrieval. Neural correlates common to both recent and remote time periods were identified, including the hippocampus, medial prefrontal, and frontopolar cortices, and the forceps minor and left hippocampal portion of the cingulum bundle. Regions exclusively implicated in each time period were also identified. The integrity of the anterior temporal cortices was related to the retrieval of remote memories, whereas the posterior cingulate cortex emerged as a structure significantly associated with recent autobiographical memory retrieval. This study represents the first investigation of the grey and white matter correlates of remote and recent autobiographical memory retrieval in neurodegenerative disorders. Our findings demonstrate the importance of core brain structures, including the medial prefrontal cortex and hippocampus, irrespective of time period, and point towards the contribution of discrete regions in mediating successful retrieval of distant versus recently experienced events

Syntactic comprehension deficits across the FTD-ALS continuum

To establish the frequency, severity, relationship to bulbar symptoms, and neural correlates of syntactic comprehension deficits across the frontotemporal dementia–amyotrophic lateral sclerosis (FTD-ALS) disease spectrum. In total, 85 participants were included in the study; 20 amyotrophic lateral sclerosis (ALS), 15 FTD-ALS, 27 progressive nonfluent aphasia (PNFA), and 23 controls. Syntactic comprehension was evaluated in ALS, FTD-ALS, PNFA, and controls using the Test for Reception of Grammar. Voxel-based morphometry examined neuroanatomical correlates of performance. Syntactic comprehension deficits were detected in 25% of ALS (p = 0.011), 92.9% of FTD-ALS (p < 0.001), and 81.5% of PNFA (p < 0.001) patients. FTD-ALS was disproportionately impaired compared to PNFA. Impaired Test for Reception of Grammar performance was frequent in ALS with early bulbar involvement but did not correlate with bulbar impairment overall. Left peri-insular atrophy correlated with syntactic comprehension deficits. Syntactic comprehension deficits are frequent in FTD-ALS, more severe than in PNFA, and related to left peri-insular atrophy. A significant minority of ALS patients are impaired, but the relationship between bulbar symptoms and syntactic impairment is not understood

Back to Analogue: Self-Reporting for Parkinson’s Disease.

We report the process used to create artefacts for self-reporting Parkinson's Disease symptoms. Our premise was that a technology-based approach would provide participants with an effective, flexible, and resilient technique. After testing four prototypes using Bluetooth, NFC, and a microcontroller we accomplished almost full compliance and high acceptance using a paper diary to track day-to-day fluctuations over 49 days. This diary is tailored to each patient's condition, does not require any handwriting, allows for implicit reminders, provides recording flexibility, and its answers can be encoded automatically. We share five design implications for future Parkinson's self-reporting artefacts: reduce participant completion demand, design to offset the effect of tremor on input, enable implicit reminders, design for positive and negative consequences of increased awareness of symptoms, and consider the effects of handwritten notes in compliance, encoding burden, and data quality

The prevalence of mild cognitive impairment in diverse geographical and ethnocultural regions: The COSMIC Collaboration

Background Changes in criteria and differences in populations studied and methodology have produced a wide range of prevalence estimates for mild cognitive impairment (MCI). Methods Uniform criteria were applied to harmonized data from 11 studies from USA, Europe, Asia and Australia, and MCI prevalence estimates determined using three separate definitions of cognitive impairment. Results The published range of MCI prevalence estimates was 5.0%-36.7%. This was reduced with all cognitive impairment definitions: performance in the bottom 6.681% (3.2%-10.8%); Clinical Dementia Rating of 0.5 (1.8%-14.9%); Mini-Mental State Examination score of 24-27 (2.1%-20.7%). Prevalences using the first definition were 5.9% overall, and increased with age (P < .001) but were unaffected by sex or the main races/ethnicities investigated (Whites and Chinese). Not completing high school increased the likelihood of MCI (P = .01). Conclusion Applying uniform criteria to harmonized data greatly reduced the variation in MCI prevalence internationally

Memories and Feelings of Music and Words in the Dementias

To date, very little is known about the memories and feelings of music and words in the dementias. And yet, these are skills we accomplish without much effort and are integral to our social milieu. Whether or not these aspects of knowledge are similarly affected across different dementia syndromes was investigated in this thesis using behavioural and neuroimaging tools. Results showed that ones memory for previously known famous tunes and also the ability to identify feelings conveyed through music and words is most impaired in individuals with the syndrome of semantic dementia. These aspects of cognition, in comparison, remain relatively well-preserved in patients with Alzheimers disease or another condition called behavioural-variant frontotemporal dementia. Distinct profiles of impairment across dementia types may have potential diagnostic and therapeutic value for clinicians and caregivers of loved ones with a dementia. Analysis of brain MRI showed that loss of knowledge for memories and feelings of music was associated with atrophy of the bilateral anterior temporal lobes. Interestingly, the right temporal pole appear critical for memories of music and overlapped with areas known to be important for the recognition of famous faces. In contrast, the identification of feelings in music was, interestingly, associated with left-sided temporal structures previously attributed principally to language and verbal semantics. Overlap in the processing of differing conceptual domains contribute to our understanding of the neural basis of semantic memory. The work presented in this thesis, therefore, illustrates the continuing clinical importance and contribution to cognitive neuroscience of studies involving patients with dementias

Cognitive decline in logopenic aphasia: More than losing words

OBJECTIVE: To track cognitive and language changes over time in patients with logopenic (lv-PPA) and semantic (sv-PPA) variants of primary progressive aphasia (PPA). METHODS: Thirteen consecutive patients with lv-PPA and 11 patients with sv-PPA underwent yearly evaluation for a mean of 3 years. Nineteen patients (11 lv-PPA, 8 sv-PPA) had Pittsburgh compound B PET scans. Outcome variables included the Mini-Mental State Examination, Addenbrooke's Cognitive Examination-revised (ACE-R) with its 5 cognitive subscores, and 3 language tasks based on single word processing. Mixed-models regressions were used to estimate the differential rate of decline between cohorts. RESULTS: Despite equivalent level of baseline impairment, the lv-PPA cohort showed more rapid and generalized cognitive decline that involved nonverbal domains, with the majority of cases meeting criteria for dementia within 12 months. By contrast, cognitive changes in the sv-PPA cohort were slower and remained confined to verbally mediated tasks. CONCLUSIONS: Patients with lv-PPA are on the cusp of global dementia that typically develops quite rapidly, contrasting with the long period of circumscribed semantic impairment seen in patients with sv-PPA. The ACE-R appears capable of monitoring decline, which is relevant to therapeutic trials