Joanna Mitchell

Activities of daily living in frontotemporal dementia and Alzheimer disease.

Objective: To evaluate activities of daily living (ADLs) in three clinical variants of frontotemporal dementia and the relationship to cognitive dysfunction. Methods: Fifty-nine patients and caregivers participated in this cross-sectional study: behavioral variant frontotemporal dementia (bv-FTD, n = 15), progressive nonfluent aphasia (PNFA, n = 10), semantic dementia (n = 15), and Alzheimer disease (AD, n = 19). Caregivers were interviewed with the Disability Assessment for Dementia (DAD) to provide two outcome measures about ADLs: basic and instrumental ADLs (BADLs, IADL). In addition, patients were rated on the Clinical Dementia Rating Scale (CDR), and performance on cognitive measures (Addenbrookes Cognitive Examination Revised [ACE-R]) was assessed. Results: On the DAD, the bv-FTD group was most affected (56% of normal), whereas PNFA and semantic dementia patients were least impaired (83% and 85%); AD was intermediate (76%). The opposite pattern was seen on the ACE-R, where PNFA and semantic dementia groups were most affected, and bv-FTD showed least impairment; AD was again intermediate. Scores on the DAD did not correlate with cognitive measures, CDR, or disease duration. We further analyzed which aspect of ADLs was most affected, and a unique pattern of deficits emerged for the bv-FTD group (initiation affected > planning > execution for BADLs). Conclusion: Frontotemporal dementia has a devastating effect on activities of daily living, which is of considerable importance to caregivers and not captured by bedside cognitive tests.

Clinical significance of lobar atrophy in frontotemporal dementia: application of an MRI visual rating scale.

Background/Aims: The status of imaging findings in the clinical diagnosis of frontotemporal dementia (FTD) remains uncertain; while they may be supportive of a diagnosis of frontotemporal dementia, they are not mandatory. Our aim was to assess patterns of lobar atrophy in a large sample of clinically defined, prospectively studied, patients using a magnetic resonance image (MRI) rating scale, to (1) determine whether imaging findings warrant a more prominent position in FTD diagnosis and (2) correlate the extent of lobar atrophy with clinical data. Methods: We adapted a recently devised post mortem rating scale for FTD to rate lobar atrophy on MRI scans. The areas rated included the frontal cortex and both anterior and posterior temporal regions bilaterally. All available brain scans from all patients seen in the Cambridge Dementia Clinic (n = 258) diagnosed as having FTD, together with controls (n = 20), were used to assess the reliability of the method. A subset of these (n = 121) were used for clinico-anatomic analysis. Results: The scale proved quick and reliable (intra-, inter-rater k = 0.80, 0.67). MRI scans were abnormal in the majority of patients (75%), with focal atrophy present in 100% of semantic dementia (SD) patients. By contrast, nearly half (47%) of the patients with clinical behavioural variant FTD had scans within the normal range. Behavioural cases with normal scans generally had fewer cognitive deficits and milder functional impairment than those with abnormal scans, yet displayed a clinically indistinguishable behavioural syndrome. They were not, however, simply at an earlier stage of the disease. Conclusions: MRI findings should form part of the diagnostic criteria for SD; the absence of atrophy on MRI in many behavioural cases raises the prospect that the behavioural syndrome of FTD is not specific for patients with a neurodegenerative disease.

Estimating energy expenditure by heart-rate monitoring without individual calibration.

UNLABELLED Heart rate monitoring has been shown to be a valid method for measuring free-living energy expenditure at the group level, but its use in large-scale studies is limited by the need for an individual calibration of the relationship between heart rate and energy expenditure. PURPOSE To determine whether energy expenditure can be estimated from heart rate monitoring without individual calibration in epidemiological studies. METHODS Our previously validated heart rate monitoring method relies on measuring individual calibration parameters obtained from resting energy expenditure and the regression line between energy expenditure and heart rate during exercise. We developed prediction equations for these parameters using easily measured variables in a population-based study of 789 individuals. The predictive ability of these parameters was tested in a separate population-based sample (N = 97). RESULTS Physical activity level (PAL = total energy expenditure/basal metabolic rate) using the four estimated parameters was correlated with PAL using the measured parameters (r = 0.82, P < 0.01). Comparison of measured and estimated PAL showed that 97.9% of the scores were placed in the same or adjacent quartile. CONCLUSION A combination of simple measurements and heart rate monitoring produces estimates of energy expenditure that are highly correlated with those obtained using full individual calibration. This simplification of the heart rate monitoring method could extend its use in ranking individuals in epidemiological studies.

Measuring progression in frontotemporal dementia Implications for therapeutic interventions

Background: There is a need for instruments which can measure progression of disease in frontotemporal dementia (FTD), particularly with respect to the assessment of potential therapeutic agents. Methods: The Cambridge Early Onset Dementia Clinic database was reviewed for all prospectively enrolled cases of FTD with documented scores on the Mini-Mental State Examination (MMSE) or Addenbrooke’s Cognitive Examination (ACE) on at least two occasions. We identified 50 cases fulfilling these criteria: pathologic confirmation was present in 11 of 16 patients who had died, 12 of the remainder had imaging abnormalities on their initial scans, and 22 had structural scans no different from controls. We compared these groups to a cohort with early AD (n = 25) and healthy controls (n = 10). Results: There was clear cognitive decline (measured by the MMSE and ACE) in patients who had died, and those with documented atrophy on initial MRI scan. In contrast, patients with FTD with normal scans showed no change in cognitive scores over a much longer interval, and serial ACE measurements paralleled those of controls. Power calculations showed that the inclusion of these patients with FTD would significantly increase the number of cases needed in any therapeutic trial. Conclusion: Addenbrooke’s Cognitive Examination is a simple monitoring tool which can detect progression of disease in frontotemporal dementia over a 1- to 2-year interval without the need for serial imaging. We estimated that a clinical trial that enrolled subjects with abnormal MR scans would require 135 subjects per group to detect a small effect, and 35 for a medium effect.

Predicting Rapid Clinical Progression in Amnestic Mild Cognitive Impairment

Background/Aims: We investigated whether an initial neuropsychological assessment could predict rapid progression over 12 months, from amnestic mild cognitive impairment (aMCI) to Alzheimer’s disease (AD). Methods: A longitudinal study compared the neuropsychological profiles of 27 normal controls and 18 aMCI patients at baseline and 12 months. Results: At 12 months, 24 control subjects followed up remained cognitively normal. 7 aMCI patients (6 multiple-domain aMCI and 1 single-domain aMCI) progressed to AD, and 11 were non-progressors. Prognosis was best captured by a combination of associative learning, the paired associate learning task (PAL), and global cognition, the Addenbrooke’s Cognitive Examination (ACE). Conclusion: The PAL and ACE can sensitively detect meaningful differences in scores at baseline and may be used as prognostic indicators. Multiple-domain aMCI patients progressed rapidly to AD and may be more usefully labelled as early stage AD.

Memory complaints in mild cognitive impairment, worried well, and semantic dementia patients.

Complaints related to memory are characteristic of normal ageing, affective disorders, and are a cardinal feature of amnestic mild cognitive impairment (aMCI), the proposed prodrome to Alzheimer disease proper. The aim of this study was to investigate the profile of subjective memory complaints in different cognitive syndromes. Subjective memory was assessed using the Cambridge Memory Complaints Questionnaire consisting of 20 questions about everyday aspects of memory. This was completed by 22 “worried well” (WW), 85 aMCI, and 40 semantic dementia (SD) patients at first presentation to a memory clinic. All patients were followed up for 2 years. A principal component factor analysis revealed 5 principal factors pertaining to working, episodic, topographical, and semantic memory. All factors, except topographical memory, reliably differentiated SD patients from other groups, with aMCI and WW patients complaining significantly more about working and episodic memory, and SD patients complaining significantly more about semantic memory. WW and aMCI patients, however, could not be differentiated, even those aMCI patients who progressed to dementia. Memory complaints are strikingly similar to the description of typical core deficits in SD patients. The sole reliance on memory complaints for insight into memory functioning and diagnosing aMCI is problematic.

Reasons for non-participation in a primary care-based physical activity trial: a qualitative study

Objectives To explore reasons for non-participation in a primary care-based physical activity trial and understand how these may contribute to recruitment of non-representative research samples. We also aimed to elicit non-participants’ own recommendations for enhancing trial uptake in primary care. Design Semistructured telephone interviews with non-participants to a randomised controlled trial of a very brief intervention for promoting physical activity conducted in primary care (the Very Brief Interventions trial), with thematic analysis of interview transcripts. Setting 5 general practice (GP) surgeries in the East of England, UK. Participants Interviews were completed with 10 female and 6 male non-participants of white ethnicity and aged between 40 and 71 years. 13 of the 16 interviewees were either active or moderately active according to the GP Physical Activity Questionnaire (GPPAQ). Results Interviewees discussed a range of reasons for non-participation. These included beliefs surrounding the personal relevance of the trial based on preconceptions of intervention content. Many interviewees considered themselves either sufficiently active or too functionally limited to increase activity levels further, so rendering participation pointless in their view. Other identified barriers included a lack of free time, for trial participation and for increasing physical activity, and dissatisfaction with appointment scheduling systems in place at GP surgeries. Interviewees questioned the appropriateness of primary care as a context for delivering interventions to promote physical activity. In general, interviewees were positively disposed towards the idea of trial participation, especially if personal benefits are made salient, but suggested that interventions could be delivered in a different setting such as the internet. Conclusions To increase participation in physical activity promotion trials conducted in primary care, the content of invitation materials and procedures for contacting potential participants require reconsideration. Specific recommendations include streamlining intervention materials and enhancing their relevance to the health concerns of invitees. Trial registration number ISRCTN72691150; Pre-results.