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

Progression in behavioral variant frontotemporal dementia:A longitudinal study

Importance: A gap in the literature exists regarding progression in behavioral variant frontotemporal dementia (BVFTD). Guidance is needed concerning markers that will enable clinicians to discriminate FTD more effectively from phenocopies and to identify factors that determine progression and thereby prognosis.  Objectives: To observe longitudinal outcomes and progression in probable and possible BVFTD in accordance with international diagnostic criteria and to identify features that may aid clinicians to prognosticate better in cases of possible BVFTD.  Design, Setting, and Participants: Longitudinal cohort study performed in a specialist tertiary FTD research clinic. Fifty-eight consecutive patients were followed up longitudinally from January 1, 2008, through December 31, 2013, and classified as having possible, probable, or definite BVFTD at presentation and latest review. Final follow-up was completed on December 31, 2013, and data were analyzed from January 1 to August 1, 2014.  Main Outcomes and Measures: Clinical, pathological, genetic, neuropsychological, and neuroimaging data were analyzed to categorize patients, to compare differences between groups with changed and unchanged diagnoses, to determine rates of progression in BVFTD, and to identify prognostic features in possible BVFTD.  Results: At presentation, 38 of the 58 patients fulfilled criteria for probable BVFTD; of these, 36 continued to satisfy probable criteria or underwent conversion to definite criteria over time. The remaining 20 patients satisfied possible criteria only, and 11 of these patients changed categories over time to probable or definite BVFTD and showed progression on cognitive and functional measures (termed changed status). Of these 11 patients, 8 (73%) carried the C9orf72 expansion. A positive family history, memory impairment, and clinical abnormalities at presentation were key features of progression (P < .05). A continuum of neuropsychological scores, progression rates, and atrophy severity emerged across patients in probable, possible, changed status, and nonchanged status groups; patients with probable BVFTD exhibited the most severe abnormalities.  Conclusions and Relevance: Behavioral variant FTD shows variable progression over time. Clinicians can use a detailed neurologic and cognitive assessment to identify key predictive features of progression when faced with possible BVFTD, whereas a diagnosis of probable BVFTD is accurate in a clinical setting

Should I trust you? Learning and memory of social interactions in dementia

Social relevance has an enhancing effect on learning and subsequent memory retrieval. The ability to learn from and remember social interactions may impact on susceptibility to financial exploitation, which is elevated in individuals with dementia. The current study aimed to investigate learning and memory of social interactions, the relationship between performance and financial vulnerability and the neural substrates underpinning performance in 14 Alzheimer's disease (AD) and 20 behavioural-variant frontotemporal dementia (bvFTD) patients and 20 age-matched healthy controls. On a “trust game” task, participants invested virtual money with counterparts who acted either in a trustworthy or untrustworthy manner over repeated interactions. A non-social “lottery” condition was also included. Participants’ learning of trust/distrust responses and subsequent memory for the counterparts and nature of the interactions was assessed. Carer-rated profiles of financial vulnerability were also collected. Relative to controls, both patient groups showed attenuated learning of trust/distrust responses, and lower overall memory for social interactions. Despite poor learning performance, both AD and bvFTD patients showed better memory of social compared to non-social interactions. Importantly, better memory for social interactions was associated with lower financial vulnerability in AD, but not bvFTD. Learning and memory of social interactions was associated with medial temporal and temporoparietal atrophy in AD, whereas a wider network of frontostriatal, insular, fusiform and medial temporal regions was implicated in bvFTD. Our findings suggest that although social relevance influences memory to an extent in both AD and bvFTD, this is associated with vulnerability to financial exploitation in AD only, and is underpinned by changes to different neural substrates. Theoretically, these findings provide novel insights into potential mechanisms that give rise to vulnerability in people with dementia, and open avenues for possible interventions

Dementia in Latin America:Assessing the present and envisioning the future

The demographic structure of Latin American countries (LAC) is fast approaching that of developing countries, and the predicted prevalence of dementia in the former already exceeds the latter. Dementia has been declared a global challenge, yet regions around the world show differences in both the nature and magnitude of such a challenge. This article provides evidence and insights on barriers which, if overcome, would enable the harmonization of strategies to tackle the dementia challenge in LAC. First, we analyze the lack of available epidemiologic data, the need for standardizing clinical practice and improving physician training, and the existing barriers regarding resources, culture, and stigmas. We discuss how these are preventing timely care and research. Regarding specific health actions, most LAC have minimal mental health facilities and do not have specific mental health policies or budgets specific to dementia. In addition, local regulations may need to consider the regional context when developing treatment and prevention strategies. The support needed nationally and internationally to enable a smooth and timely transition of LAC to a position that integrates global strategies is highlighted. We focus on shared issues of poverty, cultural barriers, and socioeconomic vulnerability. We identify avenues for collaboration aimed to study unique populations, improve valid assessment methods, and generate opportunities for translational research, thus establishing a regional network. The issues identified here point to future specific actions aimed at tackling the dementia challenge in LAC.Alzheimer's Society UK grants AS-R42303 AS-SF-14-008 CONICYT-Fondecyt 117001

Examining the presence and nature of delusions in Alzheimer's disease and frontotemporal dementia syndromes

Objectives Abnormal beliefs and delusions have been reported in some people with dementia, however, the prevalence of delusions, and their neurocognitive basis has been underexplored. This study aimed to examine the presence, severity, content and neural correlates of delusions in a large, well-characterised cohort of dementia patients using a transdiagnostic, cross-sectional approach. Methods Four-hundred and eighty-seven people with dementia were recruited: 102 Alzheimer's disease, 136 behavioural-variant frontotemporal dementia, 154 primary progressive aphasia, 29 motor neurone disease, 46 corticobasal syndrome, 20 progressive supranuclear palsy. All patients underwent neuropsychological assessment and brain magnetic resonance imaging, and the Neuropsychiatric Inventory was conducted with an informant, by an experienced clinician. Results In our cohort, 48/487 patients (10.8%) had delusions. A diagnosis of behavioural-variant frontotemporal dementia (18.4%) and Alzheimer's disease (11.8%) were associated with increased risk of delusions. A positive gene mutation was observed in 11/27 people with delusions. Individuals with frequent delusions performed worse on the Addenbrooke's Cognitive Examination (p = 0.035), particularly on the orientation/attention (p = 0.022) and memory (p = 0.013) subtests. Voxel-based morphometry analyses found that increased delusional psychopathology was associated with reduced integrity of the right middle frontal gyrus, right planum temporale and left anterior temporal pole. Conclusion Our results demonstrate that delusions are relatively common in dementia and uncover a unique cognitive and neural profile associated with the manifestation of delusions. Clinically, delusions may lead to delayed or misdiagnosis. Our results shed light on how to identify individuals at risk of neuropsychiatric features of dementia, a crucial first step to enable targeted symptom management

Dementia in Latin America : paving the way towards a regional action plan

Regional challenges faced by Latin American and Caribbean countries (LACs) to fight dementia, such as heterogeneity, diversity, political instabilities, and socioeconomic disparities, can be addressed more effectively grounded in a collaborative setting based on the open exchange of knowledge. In this work, the Latin American and Caribbean Consortium on Dementia (LAC-CD) proposes an agenda for integration to deliver a Knowledge to Action Framework (KtAF). First, we summarize evidence-based strategies (epidemiology, genetics, biomarkers, clinical trials, nonpharmacological interventions, networking and translational research) and align them to current global strategies to translate regional knowledge into actions with transformative power. Then, by characterizing genetic isolates, admixture in populations, environmental factors, and barriers to effective interventions and mapping these to the above challenges, we provide the basic mosaics of knowledge that will pave the way towards a KtAF. We describe strategies supporting the knowledge creation stage that underpins the translational impact of KtAF

Disturbance of emotion processing in frontotemporal dementia : a synthesis of cognitive and neuroimaging findings

Accurate processing of emotional information is a critical component of appropriate social interactions and interpersonal relationships. Disturbance of emotion processing is present in frontotemporal dementia (FTD) and is a clinical feature in two of the three subtypes: behavioural-variant FTD and semantic dementia. Emotion processing in progressive nonfluent aphasia, the third FTD subtype, is thought to be mostly preserved, although current evidence is scant. This paper reviews the literature on emotion recognition, reactivity and expression in FTD subtypes, although most studies focus on emotion recognition. The relationship between patterns of emotion processing deficits and patterns of neural atrophy are considered, by integrating evidence from recent neuroimaging studies. The review findings are discussed in the context of three contemporary theories of emotion processing: the limbic system model, the right hemisphere model and a multimodal system of emotion. Results across subtypes of FTD are most consistent with the multimodal system model, and support the presence of somewhat dissociable neural correlates for basic emotions, with strongest evidence for the emotions anger and sadness. Poor emotion processing is evident in all three subtypes, although deficits are more widespread than what would be predicted based on studies in healthy cohorts. Studies that include behavioural and imaging data are limited. Future investigations combining these approaches will help improve the understanding of the neural network underlying emotion processing. Presently, longitudinal investigations of emotion processing in FTD are lacking, and studies investigating emotion processing over time are critical to understand the clinical manifestations of disease progression in FTD.18 page(s

Considering the impact of large-scale network interactions on cognitive control

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Behavioural variant frontotemporal dementia:At the interface of interoception, emotion and social cognition?

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Ecological assessment of emotional enhancement of memory in progressive nonfluent aphasia and Alzheimer's disease

Background: Events which are imbued with emotion are typically remembered vividly and with more confidence than similar non-emotional events. The extent that emotional enhancement of memory is compromised in neurodegenerative disorders is unclear, despite differential effects of dementia on emotion processing ability. Objective: To examine emotional enhancement of memory using an ecologically valid task in progressive nonfluent aphasia (PNFA), an expressive language subtype of frontotemporal dementia, in comparison to Alzheimer's disease (AD) and matched-controls. Methods: Twenty-five dementia patients (13 PNFA, 12 AD) and 10 controls viewed either an emotionally arousing or a closely matched non-emotional story. Multiple-choice recognition memory was tested after a 1-hour delay. The alternate story was presented two weeks later. Results: PNFA showed a similar level of memory for the emotional and neutral story, whereas both controls and AD remembered significantly more details from the emotional than the neutral story. Correlation analyses indicated that in PNFA, emotional story memory correlated with reduced emotion recognition, whereas in AD, neutral story memory correlated with visual recall memory performance only. Furthermore, in PNFA, reduced emotional memory enhancement was associated with increased carer stress and depression. Conclusion: Emotional memory enhancement is absent in PNFA, whereas emotion facilitates memory for real-life events in AD. Disrupted emotional memory enhancement in PNFA is associated with reduced emotion recognition ability, suggesting that widespread emotion processing dysfunction is present in this disease. Crucially, loss of emotional enhancement influences carer wellbeing, which represents an important avenue for future studies to examine.10 page(s