P1-114 Mild cognitive impairment: stability and predictability of neuropsychological test performance over time

Poster Session PI: Diagnosis and Disease Progression - Neuropsychological recognised target items from semantically related foils, gave their locations on the page and 'when' they saw the item i.e. which section of the test it was in. Results: One-way ANOVA revealed significant effects of group for all task components (familiarity: F(3,54) = 22.3, p < 0.001, naming F(3,54) = 40.624, p < 0.001, recognition F(3,54) = 6.2, p -- 0.001, placing: F(3,54) = 6.4, p = 0.001, source: F(3,54) = 4.5, p < 0.05, weighted source: F(3,53) = 6.8, p = 0.001).Post-hoe testing indicated impaired performance in the MCI patients on all tasks (p < 0.05), while the semantic dementia group had deficits in the familiarity (p < 0.001), naming (p < 0.001) and recognition (p = 0.036) of items. The fvFTD group exhibited a mild naming deficit (p = 0.014) and preserved recognition and placing with a trend towards impairment on the source task. Performance on placing and source did not significantly deviate from the control range in SD and furthermore, the SD and MCI groups could be successfully differentiated from each other on the basis of naming (p < 0.001). Conclusions: These findings suggest that tasks that simultaneously tap different cognitive abilities might be usefully applied to the differentiation of MCI from other dementia groups. Testing of larger patient groups is ongoing.

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NEUROPSYCHOLOGICAL CHARACTERIZATION O F DEMENTIA WITH LEWY BODIES IN A COMMUNITY-BASED, AUTOPSY S A M P L E O F DEMENTIA

Matt L. Kraybill* 1, James B. Leverenz 1,2, Debby W. Tsuang 1,2 Linda Teri 2, Wayne C. McCormick 2, James D. Bowen 2, Walter A. Kukull 2, Eric B. Larson 2, Monique M. Cherrier 1,2.1 VAPSHCS, Seattle,

WA, USA; 2University of Washington, Seattle, WA, USA. Contact e-mail: mart.kraybiU @med. va.gov

Background: Lewy body (LB) pathology is a frequent finding in dementia studies. Clinical studies of dementia with Lewy bodies (DLB) suggest that patients with DLB have a unique clinical picture. Previous neuropsychological studies have found that patients with DLB have less memory impairment and more executive dysfunction than patients with Alzheimer's disease (AD). However, there is limited data on the neuropsychological characteristics of DLB in the community, particularly in autopsy-confirmed cases. Objective(s): This study retrospectively examines the neuropsychological profile of DLB in a community-based, autopsy sample of dementia. Methods: One hundred sixty-seven subjects met clinical criteria for dementia and were subsequently classified according to post-mortem evidence of LBs by alpha-synuclein immunostaining, and Braak staging for AD pathology using a silver stain. Sixty subjects evidenced AD pathology without LBs and were classified as AD. Seventy-nine subjects evidenced LBs and AD pathology together and were classified as AD-DLB. Twenty-eight subjects evidenced LB pathology alone, without significant AD pathology, and were classified as dementia with Lewy bodies (DLB). There were no significant differences between groups in initial Mini-Mental Exam (MMSE) scores or education. Results: A comparison of MMSE as well as Dementia Rating Scale (DRS) scores over time revealed a significant difference between groups (p < 0.05) with AD-DLB subjects demonstrating the most rapid rate of decline, followed by the AD subjects, and then DLB. AD subjects performed worse than DLB subjects on memory measures (Fuld Object Memory - delayed recall, WMS Logical Memory - immediate and delayed recall; p < 0.05) and verbal tasks (Boston Naming; p < 0.05). DLB subjects were more impaired than AD subjects on executive function tasks (Trails B Time, Wais-R Similarities; p < 0.05) and attention (Wals-R Digit Span; p < 0.05). Conclusions: These results suggest that even in a community-based sample of older and more medically complicated subjects with dementia, there are important neuropsychological differences between dementia subtypes. In particular, AD and AD-DLB had more severe memory impairment, while DLB alone was associated with more severe executive dysfunction. However, despite a similar neuropsychological profile, AD-DLB patients appeared to have a more malignant course than observed in AD.

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COMPARISON OF A COMPUTERIZED COGNITIVE S C R E E N I N G P R O G R A M TO C L I N I C A L IMPRESSION OF COGNITIVE FUNCTION

Edward Zamrini*, Daniel Marson, H. Randall Griffith, Sara Krzywanski, Lindy E. Harrell, Alfred Bartolucci. University of Alabama at Birmingham,

Birmingham, AL, USA. Contact e-mail: [email protected]

Background: Computerized testing may prove useful in discriminating subjects with Mild Cognitive Impairment (MCI) from normals and from Alzheimer's Disease (AD) patients. Objective(s): To investigate the reliability of the CANTAB (Cambridge Neuropsychological Test Automated Battery) in discriminating normal cognition, MCI, and AD in a well-defined group of older adults participating in a longitudinal research study. Methods: All subjects were volunteers participating in the University of Alabama at Birmingham Alzheimer's Disease Research Center Longitudinal Study. Subjects were evaluated clinically and assigned at consensus conferences to one of the three diagnostic categories by 2 neurologists and 2 neurpsychologists experienced in dementia. Assignment to diagnostic category according to the CANTAB test battery was compared to the consensus assingment considered the gold standard. Sensitivity and specifity were also assessed for the Paired-Associate Learning (PAL) subtest of the CANTAB. Results: Subjects were t6 mild AD (8M, 8F) mean age 71.5 y. (range 51-82), 21 MCI (6M, 15F) mean age 68.0 y. (range 53-82), and 20 normal controls (5M, 15F) mean age 66.0 y. (range 54-89). One subject was excluded because he had Diffuse Lewy Body Disease. There was significant agreement between consensus diagnosis and CANTAB assignment, Kappa p-value = 0.0001. However, sensitivities and specificities were not consistently strong (see table). Sensitivity and Specifity of CANTAB and PAL assignment relative to consensus diagnosis CANTAB Diagnosis Control MCI AD

PAL Sensitivity Specificity 0.60 0.81 0.44

0.92 0.53 0.98

Diagnosis Sensitivity Specificity Control MCI AD

0.79 0.27 0.56

0.63 0.80 0.85

Conclusions: Computerized cognitive assessment batteries may be useful screens or adjuncts for detecting MCI, but do not replace appropriate clinical assessment.

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C O G N I T I V E IMPAIRMENT: STABILITY AND PREDICTABILITY OF N E U R O P S Y C H O L O G I C A L TEST P E R F O R M A N C E O V E R TIME

Celeste A. de Jager *I , Marc M. Budge 2. IOPTIMA, University of Oxford,

Oxford, United Kingdom; 2Department of Geriatric Medicine, ANU, Canberra, Australia. Contact e-mail: [email protected]

Background: Studies on Mild Cognitive Impairment (MCI) are looking for the best criteria for identifying those at risk for Alzheimers disease and other dementias. Objective: To address some of the issues surrounding the stability of MCI over time. Methods: The Challenge cohort of 157 community dwelling volunteers was assessed at 3 episodes at two-year intervals. Cognitive domains tested were episodic, semantic and working memory, attention and executive function and processing speed. Subjective memory was also assessed with the CAMDEX. Results: 20.4% of the cohort was clinically classified as MCI by episode 3. Changes in classification from episode 1 and 2 revealed 50% stability of MCI, 7.5% unstable MCI, 35% improvement to control status, and 7.5% progression from MCI to dementia. A General Linear Model showed that the most predictive measures for the MCI group included episodic memory and central executive function tests, with 38% amnestic MCI and 62% multiple cognitive domain MCI. Sensitivity and specificity of the combined z-score of a verbal and a visuospatial memory test was more sensitive to MCI than either test alone. The MCI group also showed significant decline in performance from episode I to 3 with this score. Subjective memory complaints were positive for 79% of the MCI group and 62.5% of the control group. Conclusions: Subjective

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Poster Session PI : Diagnosis and Disease Progression - Neuropsychological

memory complaint was not a good discriminator between MCI and control subjects in our community cohort. A combined standardized score of two tests was more sensitive to MCI than scores on either test alone. As stability of MCI classification was only 50%, it would be advantageous to assess subjects at more than one time point for progressive decline in cognitive performance and for better accuracy of diagnosis.

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ADCS PREVENTION INSTRUMENT PROJECT: DEVELOPMENT OF COGNITIVE INSTRUMENTS FOR PRIMARY PREVENTION CLINICAL TRIALS

David P. Salmon*. UCSD, La Jolla, CA, USA. Contact e-mail: dsalmon @ucsd.edu

Background: As large-scale clinical trials are developed to assess primary prevention of Alzheimer's disease (AD), it is necessary to have brief, easily administered, valid, and reliable methods to assess cognition in very large samples of elderly individuals. The impact of age, education, gender, and ethnicity on such tests must be known so that appropriate boundaries for normal and impaired performance can be established. In addition, because individuals in such trials are usually cognitively intact at entry, new technologies such as web-based or telephone-based methodologies are likely to be effective, but must be validated. Objective: To develop and evaluate the validity and reliability of brief cognitive screening instruments that can be administered in a clinic, over the telephone, or via the interact. Methods: The modified MMSE and a battery of seven cognitive tests known to be sensitive to early AD (e.g., measures of delayed recall, executive functions, language, and attention) were administered to 645 elderly individuals (41.5% female, 22% minority) between the ages of 75 and 93 in a clinic setting at baseline and 3 months later. In addition, a cognitive screening questionnaire and a delayed recall test were administered over the telephone for half of the sample (randomly selected) and in the clinic for the other half. A small subsample (n = 60) also completed the latter two screening instruments through a self-administered web-based program. Results: The cognitive test battery and the home-based telephone screening tests were found to have excellent test-retest reliability. The home-based and web-based methods were also found to be valid in relation to the clinic-based methods. The impact of age, education, gender, and ethnicity, and the interaction between these characteristics, was evaluated so that appropriate demographicallyadjusted norms are available for primary prevention trials. Conclusions: The development of these valid and reliable methods to effectively and efficiently assess cognition should have a substantial positive impact on the conduct of clinical trials of potential treatments that may prevent the development of AD.

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FOCAL RETROGRADE AMNESIA: CLINICAL, NEUROPSYCHOLOGICAL AND NEUROIMAGING STUDY

Andrew J. Lamer*, Eric J. Ghadiali, Mark Doran. Walton Centre for Neurology and Neurosurgery, Liverpool, United Kingdom. Contact e-mail: a. lamer @thewaltoncentre.nhs, ak

testing was normal with no evidence of semantic problems. Verbal fluency was normal but visuospatial abilities were impaired. Brain MR imaging showed frontal and temporal lobe atrophy, more evident on the left. Conclusions: Autobiographical amnesia with preserved auditory verbal memory, associated with left temporal lobe atrophy, established a diagnosis of focal retrograde amnesia, apparently due to a failure of retrieval of autobiographical information. Alcohol abuse was the only recognised predisposing factor, although classically this is associated with anterograde memory deficit as in Korsakoff's syndrome.

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LONGITUDINAL ASSESSMENT OF C O N F R O N T A T I O N N A M I N G IN A L Z H E I M E R ' S DISEASE A N D S E M A N T I C D E M E N T I A

Peachie Moore*, Robin Hanck, Shweta Antani, Murray Grossman. University of Pennsylvania, Philadelphia, PA, USA. Contact e-mail: peachie @mail.med.upenn.edu

Background: Naming involves using the semantic representation of an object to retrieve a name. Naming diffÉculty is common in Alzheimer's Disease (AD) and Semantic Dementia (SD), but few studies have examined naming comparatively or longitudinally. Objective: A comparative longitudinal assessment of naming in AD and SD. Methods: We assessed naming longitudinally in 94 AD and 13 SD patients. AD and SD performance was converted to z-scores based on 25 matched controls because groups did not match for age [F(1,105)=5.23; p < 0.05] or education [F(1,105)=4.57; p < 0.05] when first seen, although groups matched for MMSE. Patients named 15 drawings from the Boston Naming Task at 12-month intervals on an average of 3 occasions. Concurrently, we assessed semantic memory with a 48-item semantic category membership judgment task, and assessed lexical retrieval with a semantic category naming fluency task. Results: Initially, naming was significantly less impaired in AD compared to SD [t( 105)=3.21; p < 0.01]. Z-score analyses of individual patient performance [criterion z < -1.96] showed initial impairment in 47% of AD and 62% of SD patients. Initially, AD patients were significantly less impaired for lexical retrieval than SD patients [t(105)=5.78; p < 0.01]; groups were equivalent for semantic category judgments [t(105)=0.26; ns]. Longitudinal data were assessed with Cox regression survival analyses [endpoint z-score < -3.1 (p < 0.001)]. AD and SD patients differed significantly in rate of naming decline [X2(1)=10.01; p < 0.01]. AD patients reached a 50% cumulative survival rate in 4.5 years, while SD patients took 4 years. We examined the roles of semantic memory and lexical retrieval by subgrouping AD and SD patients depending on whether they had a significant impairment [z < -1.96; p < 0.05] at presentation. When subgrouped by semantic judgment accuracy [X2(1)=5.11; p < 0.05] and lexical retrieval fluency [X2(1)=6.56; p < 0.05], decline in AD and SD differed significantly. SD patients impaired in each task reached 50% survival earlier than impaired AD patients [semantic: AD in 4.5 yrs, SD in 2yrs; retrieval: AD in 5yrs, SD in 2yrs]. Conclusions: AD and SD have impaired naming, but severity differs initially and longitudinally. SD patients are more severely impaired than AD patients at presentation, and show more rapid decline longitudinally. Rapid naming decline in SD is due to the contribution of semantic memory and lexical retrieval impairments.

Background: Focal retrograde amnesia is a rare neuropsychological finding, with variable aetiology. Objective(s): To report the clinical, neuropsychological and neuroimaging findings in a patient with focal retrograde amnesia. Methods: Longitudinal case study Results: A 64-year old man was able to give a reasonable account of current news events but could not recall his childhood, teenage or adult years, about which he produced confabulations of momentary type without insight. There was a previous history of alcohol abuse, but no witnessed seizures or head injury. Neuropsychological assessment showed a large verbal/performance IQ discrepancy in favour of verbal abilities. Memory testing showed average performance on working memory. His performance was poorer on tests of visual memory compared to auditory memory; auditory delayed recall was within the average range. On the Autobiographical Memory Interview, when his responses were compared with information from his brother it was clear that he had autobiographical amnesia for childhood, teenage and adult life. Language

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V I S U O S P A T I A L AND P S Y C H O M O T O R D E F I C I T S IN LEWY BODY DEMENTIA: IMPROVING ANTEMORTEM DIAGNOSIS

James E. Galvin*, David K. Johnson. Washington University, St Louis, MO, USA. Contact e-mail: [email protected]

Background: Cognitive decline in Lewy Body Dementia (LBD) has been associated with deficits in attention, executive function, and visuospatial abilities, but because there are few prospective longitudinal studies of wellcharacterized individuals followed to autopsy, there is little information about the contribution Lewy bodies make to cognitive impairment when there is concurrent Alzheimer disease pathology. Objective(s): We combined cognitive measures of memory, attention, visuospatial, and executive