Kate Dawson

MRC Cognition and Brain Sciences Unit, Cambridge, England, United Kingdom

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Publications (15)103.55 Total impact

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    ABSTRACT: 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. © 2014 S. Karger AG, Basel.
    Dementia and Geriatric Cognitive Disorders 09/2014; 39(1-2):1-11. · 2.79 Impact Factor
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    ABSTRACT: BACKGROUND: Behavioral variant frontotemporal dementia (bvFTD) is a common cause of younger onset dementia. Little is known about its rate of progression but a recently identified subgroup seems to have an excellent prognosis. Other determinants of survival are unclear. METHODS: We analyzed survival in a large group of clinically diagnosed bvFTD patients (n = 91) with particular attention to demographic and clinical features at presentation. Of the 91 cases, 50 have died, with pathologic confirmation in 28. RESULTS: Median survival in the whole group was 9.0 years from symptom onset, and 5.4 years from diagnosis. After the exclusion of 24 "phenocopy" cases, the analysis was repeated in a subgroup of 67 patients. The mean age at symptom onset of the pathologic group was 58.5 years and 16% had a positive family history. Their median survival was 7.6 years (95% confidence interval [CI] 6.6-8.6) from symptom onset and 4.2 years (95% CI 3.4-5.0) from diagnosis. The only factor associated with shorter survival was the presence of language impairment at diagnosis. CONCLUSIONS: Patients with definite frontotemporal dementia have a poor prognosis which is worse if language deficits are also present. This contrasts with the extremely good outcome in those with the phenocopy syndrome: of our 24 patients only 1 has died (of coincident pathology) despite, in some cases, many years of follow-up.
    Neurology. 11/2009; 73(20):1656-61.
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    ABSTRACT: Behavioral variant frontotemporal dementia (bvFTD) is a common cause of younger onset dementia. Little is known about its rate of progression but a recently identified subgroup seems to have an excellent prognosis. Other determinants of survival are unclear. We analyzed survival in a large group of clinically diagnosed bvFTD patients (n = 91) with particular attention to demographic and clinical features at presentation. Of the 91 cases, 50 have died, with pathologic confirmation in 28. Median survival in the whole group was 9.0 years from symptom onset, and 5.4 years from diagnosis. After the exclusion of 24 "phenocopy" cases, the analysis was repeated in a subgroup of 67 patients. The mean age at symptom onset of the pathologic group was 58.5 years and 16% had a positive family history. Their median survival was 7.6 years (95% confidence interval [CI] 6.6-8.6) from symptom onset and 4.2 years (95% CI 3.4-5.0) from diagnosis. The only factor associated with shorter survival was the presence of language impairment at diagnosis. Patients with definite frontotemporal dementia have a poor prognosis which is worse if language deficits are also present. This contrasts with the extremely good outcome in those with the phenocopy syndrome: of our 24 patients only 1 has died (of coincident pathology) despite, in some cases, many years of follow-up.
    Neurology 11/2009; 73(20):1656-61. · 8.25 Impact Factor
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    ABSTRACT: A great deal has been written about cognitive aspects of semantic dementia but little is known about the demography or prognosis. We describe these features in a consecutive series of 100 patients seen over a 17-year period; all cases were assessed and followed up in a specialist clinic. The mean age at diagnosis was 64.2 (+/-7.1) range 40-79 years, but 46 presented after age 65 and 7 after 75; a higher proportion than the existing literature might predict. Fifteen had a first-degree relative with dementia, but in seven this was almost certainly unrelated. Only two had relatives with young-onset dementia. There were no families with more than two affected members. The familial rate was estimated at between 2% and 7% (95% confidence interval 0-12%). Kaplan-Meier analyses indicated a 50% survival of 12.8 years (95% confidence interval 11.9-13.7); a more benign course than suggested by neuropathologically based studies. We were unable to identify any factors influencing survival. Of the 100, 34 have died, with pathological confirmation in 24; 18 had frontotemporal lobar degeneration with ubiquitin-positive inclusions (13 of 13 confirmed TAR DNA binding protein-43 positive), and 3 had classic tau-positive Pick bodies and 3 had Alzheimer's pathology. The age at diagnosis or death across the pathological subgroups was equivalent. Although semantic dementia has a strong statistical association with ubiquitin-positive pathology, it does not have the signature of familial frontotemporal lobar degeneration with ubiquitin-positive inclusions, notably the presence of intranuclear lentiform TAR DNA binding protein-43 inclusions. The age of onset is older than predicted and the course more slowly progressive than suggested by earlier studies of small groups of subjects.
    Brain 10/2009; 133(Pt 1):300-6. · 10.23 Impact Factor
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    ABSTRACT: Although it is well recognized that MCI represents a risk state for subsequent dementia, estimates of conversion vary widely according to the diagnostic criteria employed. There are currently no simple cognitive predictors of high and low risk of progression. We followed 107 non-demented non-depressed subjects from an original cohort of 124--sub-classified as follows: pure amnestic MCI (22), multi-domain MCI (54), non-amnestic MCI (10) and worried well (21). At 2 years, outcome varied considerably. Of the multi-domain MCI group 59% progressed to dementia and only 5% improved. By contrast, in pure amnestic MCI only 18% progressed and 41% improved. Of non-amnestic MCI patients 70% improved. The best predictor of progression was a combination of the Addenbrooke's cognitive examination (ACE) and the paired associate learning task (PAL), which produced high negative predictive (90%) and sensitivity (94%) values. The results indicate very different outcomes according to whether patients have pure amnestic versus multi-domain MCI. While the latter is an aggressive disorder, the former is more benign and unstable even in a clinic setting. Patients with scores >88 on the ACE and/or <14 errors on the PAL can be confidently reassured of a good prognosis.
    Journal of Neurology 05/2009; 256(9):1500-9. · 3.58 Impact Factor
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    ABSTRACT: Self administered cognitive screening test (TYM) for detection of Alzheimer's disease: cross sectional study Jeremy Brown, consultant neurologist George Pengas, clinical research fellow Kate Dawson, research nurse Lucy A Brown, honorary research assistant Philip Clatworthy, clinical research fellow ABSTRACT Objective To evaluate a cognitive test, the TYM ("test your memory"), in the detection of Alzheimer's disease. Design Cross sectional study. Setting Outpatient departments in three hospitals, including a memory clinic. Participants 540 control participants aged 18-95 and 139 patients attending a memory clinic with dementia/ amnestic mild cognitive impairment. Intervention Cognitive test designed to use minimal operator time and to be suitable for non-specialist use. Main outcome measures Performance of normal controls on the TYM. Performance of patients with Alzheimer's disease on the TYM compared with age matched controls. Validation of the TYM with two standard tests (the mini-mental state examination (MMSE) and the Addenbrooke's cognitive examination-revised (ACE-R)). Sensitivity and specificity of the TYM in the detection of Alzheimer's disease. Results Control participants completed the TYM with an average score of 47/50. Patients with Alzheimer's disease scored an average of 33/50. The TYM score shows excellent correlation with the two standard tests. A score of ≤42/50 had a sensitivity of 93% and specificity of 86% in the diagnosis of Alzheimer's disease. The TYM was more sensitive in detection of Alzheimer's disease than the mini-mental examination, detecting 93% of patients compared with 52% for the mini-mental state exxamination. The negative and positive predictive values of the TYM with the cut off of ≤42 were 99% and 42% with a prevalence of Alzheimer's disease of 10%. Thirty one patients with non-Alzheimer dementias scored an average of 39/50. Conclusions The TYM can be completed quickly and accurately by normal controls. It is a powerful and valid screening test for the detection of Alzheimer's disease. INTRODUCTION
    BMJ Clinical Research 01/2009; 338:2030. · 14.09 Impact Factor
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    ABSTRACT: To evaluate a cognitive test, the TYM ("test your memory"), in the detection of Alzheimer's disease. Cross sectional study. Outpatient departments in three hospitals, including a memory clinic. 540 control participants aged 18-95 and 139 patients attending a memory clinic with dementia/amnestic mild cognitive impairment. Cognitive test designed to use minimal operator time and to be suitable for non-specialist use. Performance of normal controls on the TYM. Performance of patients with Alzheimer's disease on the TYM compared with age matched controls. Validation of the TYM with two standard tests (the mini-mental state examination (MMSE) and the Addenbrooke's cognitive examination-revised (ACE-R)). Sensitivity and specificity of the TYM in the detection of Alzheimer's disease. Control participants completed the TYM with an average score of 47/50. Patients with Alzheimer's disease scored an average of 33/50. The TYM score shows excellent correlation with the two standard tests. A score of <or=42/50 had a sensitivity of 93% and specificity of 86% in the diagnosis of Alzheimer's disease. The TYM was more sensitive in detection of Alzheimer's disease than the mini-mental examination, detecting 93% of patients compared with 52% for the mini-mental state exxamination. The negative and positive predictive values of the TYM with the cut off of <or=42 were 99% and 42% with a prevalence of Alzheimer's disease of 10%. Thirty one patients with non-Alzheimer dementias scored an average of 39/50. The TYM can be completed quickly and accurately by normal controls. It is a powerful and valid screening test for the detection of Alzheimer's disease.
    BMJ (online) 01/2009; 338:b2030. · 17.22 Impact Factor
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    ABSTRACT: To estimate the incidence of early-onset dementias in a defined area of Cambridgeshire served by Addenbrooke's Hospital. The area selected for the study was that covered by the local authority areas of Cambridge City, East Cambridgeshire, and South Cambridgeshire. Cases were identified from the specialist memory and dementia clinics held at Addenbrooke's Hospital and were defined as those patients resident in the target area at the time of diagnosis, who were diagnosed with dementia before the age of 65 years between June 1, 2000, and May 31, 2006. No obvious pattern by sex was present. The incidence for all cases of primary dementia for the age range 45-64 years was estimated to be 11.5 cases per 100,000 person-years (95% CI 8.6-15.0). The incidence of frontotemporal dementia for the age range 45-64 years was estimated to be 3.5 cases per 100,000 person-years (95% CI 2.0-5.7); for Alzheimer disease the incidence for the same group was 4.2 (95% CI 2.5-6.6) and for Huntington disease the incidence rate of cases becoming affected (with or without dementia) was 0.8 (95% CI 0.2-2.3). If the incidence rates were extrapolated across England and Wales, in the region of 460 new cases of frontotemporal dementia and 550 new cases of Alzheimer disease could be expected each year in the 45-64 years age group.
    Neurology 12/2008; 71(19):1496-9. · 8.25 Impact Factor
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    ABSTRACT: 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.
    Alzheimer disease and associated disorders 07/2008; 22(3):227-35. · 2.88 Impact Factor
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    ABSTRACT: The Addenbrooke's Cognitive Examination (ACE) is a simple diagnostic tool bridging the gap between the very brief Mini Mental State Exam (MMSE) and much longer test batteries used by neuropsychologists which has proven extremely popular internationally. We aimed to assess the ability of the ACE to differentiate semantic dementia (SD) from Alzheimer's disease (AD). The ACE was administered to three groups: SD patients (n = 40) and two separate groups of AD patients (n = 40 in each), matched for overall ACE or MMSE score. Significant differences were found between SD and both AD groups for the ACE sub-scores of naming, reading and orientation in time. Discriminant analysis (SD versus AD) led to the formulation of a 'semantic index' (naming plus reading minus scores for serial-7s, orientation in time and drawing). Application of the semantic index to the patient data found values of less than zero to be predictive of SD rather than AD with 88% sensitivity and 90% specificity. Validation analysis in an independent sample of 24 SD and AD patients proved even more favourable. The overall ACE score is known to be a sensitive, and specific, indicator of early neurodegenerative dementia; this study shows that the ACE can also be used to detect SD through application of the semantic index.
    International Journal of Geriatric Psychiatry 05/2008; 23(4):370-5. · 3.09 Impact Factor
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    ABSTRACT: To evaluate activities of daily living (ADLs) in three clinical variants of frontotemporal dementia and the relationship to cognitive dysfunction. 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 (Addenbrooke's Cognitive Examination Revised [ACE-R]) was assessed. 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). 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.
    Neurology 06/2007; 68(24):2077-84. · 8.25 Impact Factor
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    ABSTRACT: There is a clear need for brief, but sensitive and specific, cognitive screening instruments as evidenced by the popularity of the Addenbrooke's Cognitive Examination (ACE). We aimed to validate an improved revision (the ACE-R) which incorporates five sub-domain scores (orientation/attention, memory, verbal fluency, language and visuo-spatial). Standard tests for evaluating dementia screening tests were applied. A total of 241 subjects participated in this study (Alzheimer's disease=67, frontotemporal dementia=55, dementia of Lewy Bodies=20; mild cognitive impairment-MCI=36; controls=63). Reliability of the ACE-R was very good (alpha coefficient=0.8). Correlation with the Clinical Dementia Scale was significant (r=-0.321, p<0.001). Two cut-offs were defined (88: sensitivity=0.94, specificity=0.89; 82: sensitivity=0.84, specificity=1.0). Likelihood ratios of dementia were generated for scores between 88 and 82: at a cut-off of 82 the likelihood of dementia is 100:1. A comparison of individual age and education matched groups of MCI, AD and controls placed the MCI group performance between controls and AD and revealed MCI patients to be impaired in areas other than memory (attention/orientation, verbal fluency and language). The ACE-R accomplishes standards of a valid dementia screening test, sensitive to early cognitive dysfunction.
    International Journal of Geriatric Psychiatry 12/2006; 21(11):1078-85. · 3.09 Impact Factor
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    ABSTRACT: This study investigated cross-sectional and longitudinal neuropsychological data from 55 patients: 38 with Alzheimer's disease and 18 with mild cognitive impairment (MCI). The analyses were designed to investigate two issues: the relationship of MCI to Alzheimer's disease, and that of atypical to typical Alzheimer's disease. When longitudinal data were averaged across individual patients, a consistent staging of neuropsychological deficits emerged: the selective amnesia characteristic of the MCI phase was joined next by semantic and other linguistic impairments plus emerging difficulties with demanding visuospatial tasks. A two-stage statistical procedure was used to extract underlying factors that corresponded to the severity-governed decline in neuropsychological test scores and then to the consistent deviations away from this typical longitudinal profile; i.e. identifying patterns of atypical Alzheimer's disease. The severity-based factor accounted for nearly 60% of the variance in this MCI-Alzheimer's disease longitudinal and cross-sectional database. This suggests that there is a fairly high degree of homogeneity within this group of patients, and that most of their longitudinal progression can be predicted by dementia severity alone. There were also two main patterns of atypical variation corresponding to patients with exaggerated semantic or visuospatial deficits. Although such cases may mimic more focal lobar degenerative conditions, patients with atypical Alzheimer's disease have pronounced episodic memory impairments, suggesting amnesia as a critical diagnostic feature.
    Brain 12/2003; 126(Pt 11):2350-62. · 10.23 Impact Factor
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    ABSTRACT: To estimate the prevalence of frontotemporal dementia (FTD) and other degenerative early-onset dementias in a geographically defined population. Early-onset dementia (at age <65 years) results in high psychiatric morbidity and caregiver burden. Prevalence figures are available for early-onset AD but not for FTD, a dementia that is almost invariably of early onset. Case ascertainment was by review of case records of three specialist clinic databases and inpatient admissions at a university hospital in Cambridge, United Kingdom, for patients with dementia who were <65 years of age, living in Cambridge City or East or South Cambridgeshire (population 326,019) on May 30, 2000. All the relevant health services in the area were also contacted for potential cases. Diagnosis of various dementias was based on published criteria. All patients with potential FTD were examined by the study investigators and underwent structural neuroimaging. The 1998 population estimates for the area were used to calculate age and sex prevalence with confidence intervals for AD, FTD, and other causes of dementia. A total of 108 patients (66 men and 42 women) with dementia with onset before they were 65 years of age were identified, of whom 60 were <65 years on the census date, giving an overall prevalence of 81 (95% CI, 62.8 to 104.5) per 100,000 in the 45- to 64-year age group. The prevalences of early-onset FTD and AD were the same: 15 per 100,000 (8.4 to 27.0) in the 45- to 64-year-old population. The mean age at onset of FTD was 52.8 years and there was a striking male preponderance (14:3). It is possible case ascertainment methods resulted in a relative underrepresentation of some forms of dementia. Frontotemporal dementia is a more common cause of early-onset dementia than previously recognized and appears to be more common in men.
    Neurology 07/2002; 58(11):1615-21. · 8.25 Impact Factor
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    ABSTRACT: We studied the relationship between naming and the integrity of physical and associative knowledge in a group of patients with dementia of the Alzheimer type (DAT) and matched normal controls. All subjects named 48 line drawings and later generated verbal definitions in response to the names of a subset of the 48 items, which included a minimum of six definitions for correctly named objects and six definitions for items that the subject failed to name. A comprehensive scoring system was designed for the definitions, including physical and associative features of a general and a specific type, a superordinate label, the core concept, and various categories of errors. The definitions generated by the DAT patients, even those in the minimal group, contained significantly less correct information than those of normal subjects, and definitions corresponding to unnamed items were more impoverished than those for named items. Particularly striking was the loss of core concept for unnamed items. There was also a disproportionate reduction in physical information on unnamed compared to named items. We conclude that quantitative assessment of verbal definitions is a sensitive index of semantic memory breakdown. Our findings offer some support for the hypothesis that successful naming depends upon integrity of the subset of semantic knowledge comprising physical features.
    Brain and Language 09/1996; 54(2):302-25. · 3.39 Impact Factor