- Email: [email protected]
Impact of screening and earlier intervention in Alzheimer's disease with disease-modifying agents
Poster Presentations P2
P2-101
RELIABILITY AND VALIDITY OF A SHORT FORM OF LITERACY INDEPENDENT COGNITIVE ASSESSMENT (S-LICA) IN KOREA
Jung Eun Kim1, Seong Hye Choi2, Yong S. Shim3, Jun-Young Lee4, Seung-Ho Ryu5, Dong Woo Lee6, Seol-Heui Han7, Yeo Jeong Baek8, Jee H. Jeong9, 1Department of Neurology, Ewha Womans University College of Medicine, Mokdong, Yangcheon-gu, Seoul-si, Republic of Korea; 2 Department of Neurology, Inha Univeristy College of Medicine, Sinheung-dong, Jung-gu, Incheon-si, Republic of Korea; 3Department of Neurology, Catholic University of Korea College of Medicine, Sosa-dong, Wonmi-gu, Bucheon-si, Republic of Korea; 4Department of Psychiatry, Seoul National University College of Medicine, Sindaebang-dong, Dongjak-gu, Seoul-si, Republic of Korea; 5Department of Psychiatry, Konkuk University Medical Center, Hwayang-dong, Gwangji-gu, Seoul-si, Republic of Korea; 6Department of Psychiatry, Inje University Sanggye Paik Hospital, Daehwa-dong, Ilsan seo-gu, Gyunggi-do, Republic of Korea; 7 Department of Psychiatry, Konkuk University Medical Center, Hwayang dong, Gwangjin-gu, Seoul-si, Republic of Korea; 8Department of Neurology, Ewha Womans University College of Medicine, Mokdong, Yangcheon-gu, Seoul si, Republic of Korea; 9Ewha Womans University College of Medicine, Mokdong, Yangcheon-gu, Seoul-si, Republic of Korea. Contact e-mail: [email protected] Background: The Literacy Independent Cognitive Assessment (LICA) has recently been developed for screening dementia as a useful neuropsychological test battery in the illiterate as well as the literate people. It consisted of story and words recall tests, stick design and visual recognition test, number stroop test, animal fluency, Corsi block test, calculation, visual semantics test, and naming. Factorial analysis of LICA items was used to develop the S-LICA. S-LICA consisted of words recall tests, stick design and visual recognition test, number stroop test, animal fluency, visual semantics test, and naming. The aims of this study are to cross-validate S-LICA. Methods: S-LICA was administered to informants of 81 iliteracy subjects (38 dementia, 43 normal elderly controls) and to those of 175 literacy subjects (57 dementia, 118 normal elderly controls). Stratified-clustered-random sampling was used, and 73 normal controls were matched with 62 dementia patients administered S-LICA by age and education. Test-retest data of the S-LICA was obtained from 21 subjects within a mean time interval of 28.5 days. Results: In respect to a diagnosis of dementia in literate subjects, the S-LICA (cut-off point 71.08) had a sensitivity of 94 % and specificity of 93 %, and the area under the ROC (Receiver operation characteristic) curve (Area under the curve; AUC) was 0.958 (95%CI ¼ 0.919-0.998). With respect to a diagnosis of dementia in the illiterate subjects, the S-LICA (cut-off point 68.25) had a sensitivity of 94 % and specificity of 89 %. The AUC was 0.955(95%CI ¼ 0.894-1.016). Construct validity was confirmed by evaluating the correlation between the S-LICA and K-MMSE (Korean version of Mental State Examination).The SLICA was found to have a high test-retest reliability (r ¼ 0.91). There was significantdifferences of the time reuired for test between LICA and S-LICA (p < 0.05; 32.0 6 6.9 min, 18.4 6 3.8 min) Conclusions: A short version of LICA(S-LICA) had high sensitivity, specificity and test-retest reliability which were comparable to K-MMSE. Thus, S-LICA can be a useful, brief neuropsychological test battery for the screening of dementia in the illiterate as well as the literate people P2-102
IMPACT OF SCREENING AND EARLIER INTERVENTION IN ALZHEIMER’S DISEASE WITH DISEASE-MODIFYING AGENTS
David Budd1, Leah Burns1, Zhenchao Guo1, Gil L’Italien1, Pablo Lapuerta2, Bristol-Myers Squibb, Wallingford, CT, USA; 2Bristol-Myers Squibb, Princeton, NJ, USA. Contact e-mail: [email protected]
1
Background: Patients with mild cognitive impairment and amyloidopathy are more likely to develop Alzheimer’s disease (AD), offering a window for therapeutic intervention to slow or halt disease progression, especially among patients at high risk of AD. Early screenings involving biomarkers
S343
and the use of potential disease-modifying treatments, may have significant humanistic implications for treatment strategies. Methods: Markov models simulated transitions of patient cohorts beginning in a pre-dementia state (defined by clinical and biomarker criteria, without dementia) and followed for 10 years. Hypothetical cohorts of 10,000 patients represented (1) patients treated with donepezil upon reaching moderate AD, and (2) patients treated with a hypothetical disease-modifying agent in the pre-dementia state. Transition probabilities were based upon data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), published clinical data, and estimated for the hypothetical agent. Six month cycles were used for calculation (disease state transition, costs of care, mortality). Time in disease state (pre-dementia, mild, moderate, moderately severe, severe) was computed, and costs estimated using literature review and published data. Published data provided mortality rates. The impact of screening was evaluated using positive predictive value (PPV; patients identified as pre-dementia truly at risk for transition to dementia). Results: While total life years gained by treating earlier were relatively small, the distribution of these years skewed towards milder disease. Comparing cohorts (1) and (2), treating pre-dementia patients with novel agents increased life years in pre-dementia to mild states on average from 3.2 to 4.2, while life years spent in moderate to severe AD decreased from 2.6 to 2.2. Average time in the community increased from 4.4 to 5.4 years, while time in long-term care declined from 1.3 to 0.9 years. This impact grows wider as the advantage of the novel agent increases. Screening accuracy had significant implications for cost effectiveness. Conclusions: If screening pre-dementia patients can identify those at risk for progression to dementia with a high degree of accuracy, earlier treatment with potentially diseasemodifying agents has benefit to patients: prolonging time in milder disease, reducing time in more severe disease, increasing time patients remain in the community, and reducing time spent in long-term care. P2-103
VALIDITY OF THE TELEPHONE INTERVIEW FOR COGNITIVE STATUS (TICS) AND MODIFIED TICS (TICSM) FOR MCI AND DEMENTIA SCREENING
Eun Hyun Seo1, Dong Young Lee1, Shin Gyeom Kim2, Ki Woong Kim3, Do Hoon Kim4, Bong Jo Kim5, Moon-Doo Kim6, Seong Yoon Kim7, Young Hoon Kim8, Jeong-Lan Kim9, Jee Wook Kim1, Seok Woo Moon10, Joon Hyuck Park6, Seung-Ho Ryu11, Jong Choul Yoon12, Nam Jin Lee13, Chang Uk Lee14, Jin Hyeong Jhoo15, Il Han Choo1, Jong Inn Woo1, 1Seoul National University Hospital, Seoul, Republic of Korea; 2Soonchunhyang University Bucheon hospital, Bucheon, Republic of Korea; 3Seoul National University Bundang Hospital, Seongnam, Republic of Korea; 4Univerisity Chuncheon Sacred Heart Hospital, Chuncheon, Republic of Korea; 5 Gyeongsang National University Hospital, Jinju, Republic of Korea; 6Jeju National University Hospital, Jeju, Republic of Korea; 7University of Ulsan Asan Medical Center, Seoul, Republic of Korea; 8Inje University Busan Baik Hospital, Busan, Republic of Korea; 9Chungnam National University Hospital, Daejeon, Republic of Korea; 10Konkuk University Chungju Hospital, Chungju, Republic of Korea; 11Konkuk University Hospital, Seoul, Republic of Korea; 12Gyeonggi Provincial Hospital for the Elderly, Yongin, Republic of Korea; 13Chonju Welfare Hospital for The Elderly, Chonju, Republic of Korea; 14Seoul Saint Mary’s Hospital, Seoul, Republic of Korea; 15Kangwon National University Hospital, Chunchon, Republic of Korea. Contact e-mail: [email protected] Background: This study aimed to validate both the Telephone Interview for Cognitive Status (TICS) and modified TICS (TICSm) in Korean elderly population. We also compared MCI and dementia screening ability between the TICS and TICSm. Methods: TICS and TICSm were administered to 70 cognitively normal (CN) elderly, 75 MCI, and 85 dementia subjects, with Mini-Mental State Examination (MMSE) and other cognitive and functional measures. Results: Both TICS and TICSm scores were highly correlated with other global cognitive and functional scale scores. The CN vs. dementia discrimination ability of both instrument was as excellent as that of the MMSE (sensitivity/specificity at optimal cutoff: 87.1%/90.1% for the TICS; 88.2/90.0 for the TICSm; and 85.9/91.4 for the MMSE). Although their CN vs. MCI discrimination performances were comparable to that of MMSE, they were not far from perfect (sensitivity/specificity at optimal
P2-101
RELIABILITY AND VALIDITY OF A SHORT FORM OF LITERACY INDEPENDENT COGNITIVE ASSESSMENT (S-LICA) IN KOREA
Jung Eun Kim1, Seong Hye Choi2, Yong S. Shim3, Jun-Young Lee4, Seung-Ho Ryu5, Dong Woo Lee6, Seol-Heui Han7, Yeo Jeong Baek8, Jee H. Jeong9, 1Department of Neurology, Ewha Womans University College of Medicine, Mokdong, Yangcheon-gu, Seoul-si, Republic of Korea; 2 Department of Neurology, Inha Univeristy College of Medicine, Sinheung-dong, Jung-gu, Incheon-si, Republic of Korea; 3Department of Neurology, Catholic University of Korea College of Medicine, Sosa-dong, Wonmi-gu, Bucheon-si, Republic of Korea; 4Department of Psychiatry, Seoul National University College of Medicine, Sindaebang-dong, Dongjak-gu, Seoul-si, Republic of Korea; 5Department of Psychiatry, Konkuk University Medical Center, Hwayang-dong, Gwangji-gu, Seoul-si, Republic of Korea; 6Department of Psychiatry, Inje University Sanggye Paik Hospital, Daehwa-dong, Ilsan seo-gu, Gyunggi-do, Republic of Korea; 7 Department of Psychiatry, Konkuk University Medical Center, Hwayang dong, Gwangjin-gu, Seoul-si, Republic of Korea; 8Department of Neurology, Ewha Womans University College of Medicine, Mokdong, Yangcheon-gu, Seoul si, Republic of Korea; 9Ewha Womans University College of Medicine, Mokdong, Yangcheon-gu, Seoul-si, Republic of Korea. Contact e-mail: [email protected] Background: The Literacy Independent Cognitive Assessment (LICA) has recently been developed for screening dementia as a useful neuropsychological test battery in the illiterate as well as the literate people. It consisted of story and words recall tests, stick design and visual recognition test, number stroop test, animal fluency, Corsi block test, calculation, visual semantics test, and naming. Factorial analysis of LICA items was used to develop the S-LICA. S-LICA consisted of words recall tests, stick design and visual recognition test, number stroop test, animal fluency, visual semantics test, and naming. The aims of this study are to cross-validate S-LICA. Methods: S-LICA was administered to informants of 81 iliteracy subjects (38 dementia, 43 normal elderly controls) and to those of 175 literacy subjects (57 dementia, 118 normal elderly controls). Stratified-clustered-random sampling was used, and 73 normal controls were matched with 62 dementia patients administered S-LICA by age and education. Test-retest data of the S-LICA was obtained from 21 subjects within a mean time interval of 28.5 days. Results: In respect to a diagnosis of dementia in literate subjects, the S-LICA (cut-off point 71.08) had a sensitivity of 94 % and specificity of 93 %, and the area under the ROC (Receiver operation characteristic) curve (Area under the curve; AUC) was 0.958 (95%CI ¼ 0.919-0.998). With respect to a diagnosis of dementia in the illiterate subjects, the S-LICA (cut-off point 68.25) had a sensitivity of 94 % and specificity of 89 %. The AUC was 0.955(95%CI ¼ 0.894-1.016). Construct validity was confirmed by evaluating the correlation between the S-LICA and K-MMSE (Korean version of Mental State Examination).The SLICA was found to have a high test-retest reliability (r ¼ 0.91). There was significantdifferences of the time reuired for test between LICA and S-LICA (p < 0.05; 32.0 6 6.9 min, 18.4 6 3.8 min) Conclusions: A short version of LICA(S-LICA) had high sensitivity, specificity and test-retest reliability which were comparable to K-MMSE. Thus, S-LICA can be a useful, brief neuropsychological test battery for the screening of dementia in the illiterate as well as the literate people P2-102
IMPACT OF SCREENING AND EARLIER INTERVENTION IN ALZHEIMER’S DISEASE WITH DISEASE-MODIFYING AGENTS
David Budd1, Leah Burns1, Zhenchao Guo1, Gil L’Italien1, Pablo Lapuerta2, Bristol-Myers Squibb, Wallingford, CT, USA; 2Bristol-Myers Squibb, Princeton, NJ, USA. Contact e-mail: [email protected]
1
Background: Patients with mild cognitive impairment and amyloidopathy are more likely to develop Alzheimer’s disease (AD), offering a window for therapeutic intervention to slow or halt disease progression, especially among patients at high risk of AD. Early screenings involving biomarkers
S343
and the use of potential disease-modifying treatments, may have significant humanistic implications for treatment strategies. Methods: Markov models simulated transitions of patient cohorts beginning in a pre-dementia state (defined by clinical and biomarker criteria, without dementia) and followed for 10 years. Hypothetical cohorts of 10,000 patients represented (1) patients treated with donepezil upon reaching moderate AD, and (2) patients treated with a hypothetical disease-modifying agent in the pre-dementia state. Transition probabilities were based upon data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), published clinical data, and estimated for the hypothetical agent. Six month cycles were used for calculation (disease state transition, costs of care, mortality). Time in disease state (pre-dementia, mild, moderate, moderately severe, severe) was computed, and costs estimated using literature review and published data. Published data provided mortality rates. The impact of screening was evaluated using positive predictive value (PPV; patients identified as pre-dementia truly at risk for transition to dementia). Results: While total life years gained by treating earlier were relatively small, the distribution of these years skewed towards milder disease. Comparing cohorts (1) and (2), treating pre-dementia patients with novel agents increased life years in pre-dementia to mild states on average from 3.2 to 4.2, while life years spent in moderate to severe AD decreased from 2.6 to 2.2. Average time in the community increased from 4.4 to 5.4 years, while time in long-term care declined from 1.3 to 0.9 years. This impact grows wider as the advantage of the novel agent increases. Screening accuracy had significant implications for cost effectiveness. Conclusions: If screening pre-dementia patients can identify those at risk for progression to dementia with a high degree of accuracy, earlier treatment with potentially diseasemodifying agents has benefit to patients: prolonging time in milder disease, reducing time in more severe disease, increasing time patients remain in the community, and reducing time spent in long-term care. P2-103
VALIDITY OF THE TELEPHONE INTERVIEW FOR COGNITIVE STATUS (TICS) AND MODIFIED TICS (TICSM) FOR MCI AND DEMENTIA SCREENING
Eun Hyun Seo1, Dong Young Lee1, Shin Gyeom Kim2, Ki Woong Kim3, Do Hoon Kim4, Bong Jo Kim5, Moon-Doo Kim6, Seong Yoon Kim7, Young Hoon Kim8, Jeong-Lan Kim9, Jee Wook Kim1, Seok Woo Moon10, Joon Hyuck Park6, Seung-Ho Ryu11, Jong Choul Yoon12, Nam Jin Lee13, Chang Uk Lee14, Jin Hyeong Jhoo15, Il Han Choo1, Jong Inn Woo1, 1Seoul National University Hospital, Seoul, Republic of Korea; 2Soonchunhyang University Bucheon hospital, Bucheon, Republic of Korea; 3Seoul National University Bundang Hospital, Seongnam, Republic of Korea; 4Univerisity Chuncheon Sacred Heart Hospital, Chuncheon, Republic of Korea; 5 Gyeongsang National University Hospital, Jinju, Republic of Korea; 6Jeju National University Hospital, Jeju, Republic of Korea; 7University of Ulsan Asan Medical Center, Seoul, Republic of Korea; 8Inje University Busan Baik Hospital, Busan, Republic of Korea; 9Chungnam National University Hospital, Daejeon, Republic of Korea; 10Konkuk University Chungju Hospital, Chungju, Republic of Korea; 11Konkuk University Hospital, Seoul, Republic of Korea; 12Gyeonggi Provincial Hospital for the Elderly, Yongin, Republic of Korea; 13Chonju Welfare Hospital for The Elderly, Chonju, Republic of Korea; 14Seoul Saint Mary’s Hospital, Seoul, Republic of Korea; 15Kangwon National University Hospital, Chunchon, Republic of Korea. Contact e-mail: [email protected] Background: This study aimed to validate both the Telephone Interview for Cognitive Status (TICS) and modified TICS (TICSm) in Korean elderly population. We also compared MCI and dementia screening ability between the TICS and TICSm. Methods: TICS and TICSm were administered to 70 cognitively normal (CN) elderly, 75 MCI, and 85 dementia subjects, with Mini-Mental State Examination (MMSE) and other cognitive and functional measures. Results: Both TICS and TICSm scores were highly correlated with other global cognitive and functional scale scores. The CN vs. dementia discrimination ability of both instrument was as excellent as that of the MMSE (sensitivity/specificity at optimal cutoff: 87.1%/90.1% for the TICS; 88.2/90.0 for the TICSm; and 85.9/91.4 for the MMSE). Although their CN vs. MCI discrimination performances were comparable to that of MMSE, they were not far from perfect (sensitivity/specificity at optimal