- Email: [email protected]
NEUROPSYCHOLOGICAL TOOLS TO PREDICT CONVERSION FROM AMNESTIC MILD COGNITIVE IMPAIRMENT TO DEMENTIA: THE TREDEM REGISTRY
Poster Presentations: Monday, July 25, 2016
P755
Table 1 Results from linear mixed model analyses by visual memory variables Variable
Parameter
Estimate
SE
df
t
p
95% Confidence Interval
PRM % Correct Intercept Group Evaluation Group* Evaluation
69.92 7.26 -5.37 2.91
4.47 2.42 1.75 .95
214.21 213.30 209.48 208.28
15.62 2.99 -3.05 3.06
.000 .003 .003 .002
61.10/78.74 2.47/12.05 -8.83/1.90 1.04/4.79
Intercept Croup Evaluation Group* Evaluation
67.20 5.73 -3.09 2.19
4.01 2.18 1.75 .95
208.26 207.67 195.39 194.71
16.73 2.67 -2.16 2.30
.000 .009 .032 .022
59.29/75.12 1.42/10.03 -7.26/-.33 .31/4.06
Intercept Group Evaluation Group* Evaluation
4.53 .16 -.43 .25
.38 .20 .15 .08
260.15 258.63 423.02 421.73
11.81 .75 -2.84 3.05
.000 .452 .005
3.77/5.29 -.25/.56 -.74/.13 .09/.41
Intercept Group Evaluation Group* Evaluation
86.08 -26.82 11.70 -6.08
12.60 6.04 5.06 2.74
211.48 210.66 214.67 213.44
6.83 -3.92 2.31 -2.22
.000 .000 .022 .027
61.23/110.92 -40.31/-13.33 1.72/21.67 -11.48/-.68
DMS % Correct
SSP Span length
002
PAL Total errors Adjusted
and Paired Associates Learning (PAL, total errors adjusted) using lineal mixed models. Results: The Healthy Control group showed a maintained or increased performance on all tests suggesting a practice effect on several processes involved in visual memory such as attention, recognition, recollection, learning and working memory. The MCI group showed a significant decline from baseline to the last evaluation on these visual memory processes. Conclusions: Longitudinal studies add new evidence that the CANTAB tests, PRM, DMS, SSP and PAL are useful for diagnosis of MCI across time in people with subjective cognitive complains. Further longitudinal research is necessary to determine the predictive value of these tests on the conversion to Alzheimer Disease. P2-309
LONG-TERM MEMORY FUNCTIONING IN AGEASSOCIATED MEMORY IMPAIRMENT AND MILD COGNITIVE IMPAIRMENT
Rebecca Crean1, Gary Kay2, Donald Connor3, Jamie Reiter3, Joseph Djan1, Jessica Berrett1, David Carpenter1, 1Dart NeuroScience, San Diego, CA, USA; 2Cognitive Research Corporation, St. Petersburg, FL, USA; 3 Contractor, San Diego, CA, USA. Contact e-mail: rcrean@ dartneuroscience.com Background: Drug development in age-related neurodegenerative disorders (Alzheimer’s Disease) has increasingly focused on earlier disease stages, before overt dementia. Consequently, there is a need for cognitive/memory instruments sensitive enough to detect cognitive changes that occur in pre-dementia (Mild Cognitive Impairment [MCI]) and the subtle memory changes occurring with normal aging (Age-Associated Memory Impairment [AAMI]). Traditional long-term memory tests involve a delay of 20-30 minutes; however, it is necessary to have longer retention periods to assess memory consolidation. As therapeutics are developed which target long-term memory, it is essential that validated measures of consolidation be developed to assess the efficacy of these agents. The Name Face Memory Consolidation Test (NFMCT) is a computer-based paired-associated memory testing paradigm involving name-
face associations that is designed to assess long term memory consolidation out to one-week retention intervals. This study was designed to assess long-term memory functioning and validate the NFMCT in subjects diagnosed with MCI, AAMI and healthy controls (HC). Methods: Subjects meeting diagnostic criteria for MCI (n¼25), AAMI (n¼28) and 42 matched HC’s were identified at participating research sites. MCI and AAMI diagnoses were based on neuropsychiatric examinations, and an objective history of cognitive functioning. Subjects underwent a neuropsychological assessment at Baseline. Thereafter, the NFMCT was administered at weekly intervals up to 8 weeks. Results: The groups did not differ on any demographic characteristics except age and race. Statistically significant differences between the groups were demonstrated on trials to reach criterion (p < 0.0001), long-term memory (p < 0.0001) and percentage reaching criteria (80% correct) at 7-day recall (p < 0.0001). Specifically, the HC group outperformed the AAMI and MCI groups, and the AAMI group performed better than the MCI group on these measures. Conclusions: The NFMT appears to be a sensitive measure of long-term memory, and demonstrated significant differences between AAMI, MCI and HC subjects on consolidation and acquisition measures. These results suggest that memory deficits in AAMI and MCI involve poor acquisition, consolidation and long-term memory at 1 week intervals. Further development and validation of the NFMCT, to include additional patient populations with memory deficits, appears warranted. P2-310
NEUROPSYCHOLOGICAL TOOLS TO PREDICT CONVERSION FROM AMNESTIC MILD COGNITIVE IMPAIRMENT TO DEMENTIA: THE TREDEM REGISTRY
Maurizio Gallucci1, Pierpaolo Spagnolo1, Chiara Falcone1, Maria Elena Di Battista1, Giuseppe Battistella2, Patrizia Silvia Bisiacchi3, Enrico Di Giorgi4, 1Cognitive Impairment Center, Local Health Authority n. 9 of Treviso, Treviso, Italy; 2Service of Statistics and Epidemiology, Local Health Authority n. 9 of Treviso, Italy, Italy; 3General Psychology, University of Padua, Padua, Italy; 4Health Districts of Treviso, Local Health
P756
Poster Presentations: Monday, July 25, 2016
Authority n. 9 of Treviso, Italy, Italy. Contact e-mail: galluccimaurizio@ gmail.com Background: Mild Cognitive Impairment (MCI) is widely considered a phase of transition between normality and dementia. Most of the studies of conversion from MCI to dementia has focused on amnestic MCI (aMCI) that is considered a preclinical phase of Alzheimer Disease (AD). An important goal would be to identify the neuropsychological tools that better predict conversion from MCI to dementia. Methods: Fifty-five aMCI subjects of the Treviso Dementia (TREDEM) Registry, were considered. They underwent a neuropsychological assessment in the first visit and at follow-up. Cox proportional-hazard regression models were created to measure the association between the dependent variable (dementia’s diagnosis or MCI status maintainance) and indipendent variables (neuropsychological test scores at baseline). Results: The sample (28 women and 27 men; mean age 76,82 6 5,88 ys; education 7,62 6 3,99 ys) was observed for an average time of 2,17 6 1,25 ys. A Cox backward stepwise regression showed that Rey Auditiory Verbal Learning Test, Delayed Recall (RAVLT-DR) (p¼.041) and Semantic Verbal Fluency (SVF) (p¼.031) appear to be able to predict conversion to dementia. Age and education were significant, respectively as risk (Exp B¼1,116) and protective (Exp B¼0,81) factors. Conclusions: RAVLT-DR and SVF would appear as proper tools to predict the conversion from aMCI to Dementia. P2-311
OUTCOMES FROM ROUTINE COGNITIVE SCREENING IN A HEALTH CARE SYSTEM
Leah R. Hanson1,2, Terry R. Barclay1,2, Ann M. Werner2, Lauren O. Erickson2, Jean M. Crow1,2, Soo Borson3, Kamakshi Lakshminarayan4, Michael H. Rosenbloom1,2, 1HealthPartners Center for Memory and Aging, Saint Paul, MN, USA; 2HealthPartners Institute, Bloomington, MN, USA; 3University of Washington, Seattle, WA, USA; 4University of Minnesota, Minneapolis, MN, USA. Contact e-mail: [email protected] Background: Even with routine health care, dementia often goes undiagnosed until the moderate-severe stages. The potential benefits of cognitive screening in the asymptomatic population are unclear. HealthPartners has piloted the use of the Mini-Cog as a standardized screening tool for cognitive function in patients aged 65 and older. Methods: Patients screened within specialty or primary care clinics were identified. Data from the 18 months prior to screening and the 18 months following screening were collected from the electronic medical record and included the Mini-Cog score (MC, scored 0-5), demographics, interventions received, and measures of healthcare utilization. Two definitions of screening positive were tested for the Mini-Cog (score of < 3 and < 4). Data analysis consisted of Poisson regression and normal mixed effects regression. Results: The MC was administered in 1,166 patients (average 77 yr, 58% female). Rates of patients screening positive for cognitive impairment were 16% and 32% (MC score of < 3 and < 4, respectively). Following a positive screen, documentation of diagnostic interventions (i.e. imaging, neuropsychology) were generally low (<7%), though significantly higher than after negative screens. In the 18 months following a positive screen, patients were more likely to be diagnosed with dementia or mild cognitive impairment (14% vs. 3%, p<0.001) and to receive a prescription for a dementia medication (12 % vs. 2%, p<0.001) as compared to patients with a negative screen, regardless of cutoff score used. Patients screening positive had a significantly lower overall incidence rate of office visits (-5%) in the 18 months following screening as compared to the
prior 18 months, which was more prominently seen in patients screened in primary care (-23%). Incidence of emergency room visits remained the same and hospitalizations changed significantly but differently by screen site, with significantly lower incidence in primary care screens and higher incidence in specialty care. Conclusions: Screening was associated with increased recognition of previously undetected cognitive impairment and changes in healthcare utilization. Further studies are needed to better understand what work flows may influence clinicians actions and increase the diagnostic follow-up of a positive screen.
P2-312
PREDICTING ALZHEIMER’S DISEASE IN OLDER ADULTS WITH MILD COGNITIVE IMPAIRMENT USING NEUROPSYCHOLOGICAL MEASURES: A SYSTEMATIC REVIEW AND META-ANALYSIS
Sylvie Belleville1,2, Celine Fouquet3, Carol Hudon4,5, CIMA-Q Group, 1 Institut Universitaire de Geriatrie de Montreal, Montreal, QC, Canada; 2 Universite de Montreal, Montreal, QC, Canada; 3Institut Universitaire de Geriatrie de Montreal, Montreal, QC, Canada; 4Universite Laval, Quebec, QC, Canada; 5Institut Universitaire en Sante Mentale de Quebec, Quebec, QC, Canada. Contact e-mail: [email protected] Background: An increasing number of longitudinal studies are attempting to identify tests that differentiate between persons with mild cognitive impairment (MCI) who will progress to dementia and those who will remain stable. The aim of this systematic quantitative review was to identify neuropsychological tests and cognitive domains that best predict progression to dementia of the Alzheimer type (AD). This was done by systematically reviewing and meta-analyzing the data of longitudinal studies reporting sensitivity and specificity values for neuropsychological tests to identify individuals with MCI who will decline and progress to AD in the future. Methods: The study was conducted in accordance with the PRISMA and PICOS statements. Articles were searched using appropriate key words in PubMed, Cochrane, EMBASE, PsycINFO, and ISI Web of Knowledge. Their methodological quality was assessed using the STARDem standards as well as the QUADAS, PRISMA, and Cochrane statements. Sensitivity (correct identification of progressors) and specificity (correct rejection of nonprogressors) of individual neuropsychological tests were calculated, meta-analyzed, and summarized in Forest plots. We also reviewed the sensitivity/specificity of combined tests when available. Results: 4,979 articles were initially retrieved. After the exclusion of irrelevant and duplicate articles, 26 eligible studies were analyzed. They reported data from a total of 52 neuropsychological tests (13 cognitive domains) and the mean follow-up ranged from 1 to 5 years. Many of the individual tests showed a trade-off between specificity and sensitivity, as those with good specificity values were generally of low sensitivity, and vice versa. Tests measuring general cognition (e.g., CAMCOG, ACE) or associative memory showed relatively good sensitivity but low specificity. In turn, measures of cued recall, semantic memory and language, showed relatively good specificity but low sensitivity. Tests of episodic memory, particularly those measuring delayed recall, showed a good balance between sensitivity and specificity. Sensitivity and specificity were largely improved (often > 85%) when combining memory measures with a small set of other domains. Conclusions: Individual tests vary in their sensitivity/specificity ratio and few have an appropriate balance between sensitivity and specificity. Relying on a combination of neuropsychological measures is likely to be the best approach to identify future progressors.
P755
Table 1 Results from linear mixed model analyses by visual memory variables Variable
Parameter
Estimate
SE
df
t
p
95% Confidence Interval
PRM % Correct Intercept Group Evaluation Group* Evaluation
69.92 7.26 -5.37 2.91
4.47 2.42 1.75 .95
214.21 213.30 209.48 208.28
15.62 2.99 -3.05 3.06
.000 .003 .003 .002
61.10/78.74 2.47/12.05 -8.83/1.90 1.04/4.79
Intercept Croup Evaluation Group* Evaluation
67.20 5.73 -3.09 2.19
4.01 2.18 1.75 .95
208.26 207.67 195.39 194.71
16.73 2.67 -2.16 2.30
.000 .009 .032 .022
59.29/75.12 1.42/10.03 -7.26/-.33 .31/4.06
Intercept Group Evaluation Group* Evaluation
4.53 .16 -.43 .25
.38 .20 .15 .08
260.15 258.63 423.02 421.73
11.81 .75 -2.84 3.05
.000 .452 .005
3.77/5.29 -.25/.56 -.74/.13 .09/.41
Intercept Group Evaluation Group* Evaluation
86.08 -26.82 11.70 -6.08
12.60 6.04 5.06 2.74
211.48 210.66 214.67 213.44
6.83 -3.92 2.31 -2.22
.000 .000 .022 .027
61.23/110.92 -40.31/-13.33 1.72/21.67 -11.48/-.68
DMS % Correct
SSP Span length
002
PAL Total errors Adjusted
and Paired Associates Learning (PAL, total errors adjusted) using lineal mixed models. Results: The Healthy Control group showed a maintained or increased performance on all tests suggesting a practice effect on several processes involved in visual memory such as attention, recognition, recollection, learning and working memory. The MCI group showed a significant decline from baseline to the last evaluation on these visual memory processes. Conclusions: Longitudinal studies add new evidence that the CANTAB tests, PRM, DMS, SSP and PAL are useful for diagnosis of MCI across time in people with subjective cognitive complains. Further longitudinal research is necessary to determine the predictive value of these tests on the conversion to Alzheimer Disease. P2-309
LONG-TERM MEMORY FUNCTIONING IN AGEASSOCIATED MEMORY IMPAIRMENT AND MILD COGNITIVE IMPAIRMENT
Rebecca Crean1, Gary Kay2, Donald Connor3, Jamie Reiter3, Joseph Djan1, Jessica Berrett1, David Carpenter1, 1Dart NeuroScience, San Diego, CA, USA; 2Cognitive Research Corporation, St. Petersburg, FL, USA; 3 Contractor, San Diego, CA, USA. Contact e-mail: rcrean@ dartneuroscience.com Background: Drug development in age-related neurodegenerative disorders (Alzheimer’s Disease) has increasingly focused on earlier disease stages, before overt dementia. Consequently, there is a need for cognitive/memory instruments sensitive enough to detect cognitive changes that occur in pre-dementia (Mild Cognitive Impairment [MCI]) and the subtle memory changes occurring with normal aging (Age-Associated Memory Impairment [AAMI]). Traditional long-term memory tests involve a delay of 20-30 minutes; however, it is necessary to have longer retention periods to assess memory consolidation. As therapeutics are developed which target long-term memory, it is essential that validated measures of consolidation be developed to assess the efficacy of these agents. The Name Face Memory Consolidation Test (NFMCT) is a computer-based paired-associated memory testing paradigm involving name-
face associations that is designed to assess long term memory consolidation out to one-week retention intervals. This study was designed to assess long-term memory functioning and validate the NFMCT in subjects diagnosed with MCI, AAMI and healthy controls (HC). Methods: Subjects meeting diagnostic criteria for MCI (n¼25), AAMI (n¼28) and 42 matched HC’s were identified at participating research sites. MCI and AAMI diagnoses were based on neuropsychiatric examinations, and an objective history of cognitive functioning. Subjects underwent a neuropsychological assessment at Baseline. Thereafter, the NFMCT was administered at weekly intervals up to 8 weeks. Results: The groups did not differ on any demographic characteristics except age and race. Statistically significant differences between the groups were demonstrated on trials to reach criterion (p < 0.0001), long-term memory (p < 0.0001) and percentage reaching criteria (80% correct) at 7-day recall (p < 0.0001). Specifically, the HC group outperformed the AAMI and MCI groups, and the AAMI group performed better than the MCI group on these measures. Conclusions: The NFMT appears to be a sensitive measure of long-term memory, and demonstrated significant differences between AAMI, MCI and HC subjects on consolidation and acquisition measures. These results suggest that memory deficits in AAMI and MCI involve poor acquisition, consolidation and long-term memory at 1 week intervals. Further development and validation of the NFMCT, to include additional patient populations with memory deficits, appears warranted. P2-310
NEUROPSYCHOLOGICAL TOOLS TO PREDICT CONVERSION FROM AMNESTIC MILD COGNITIVE IMPAIRMENT TO DEMENTIA: THE TREDEM REGISTRY
Maurizio Gallucci1, Pierpaolo Spagnolo1, Chiara Falcone1, Maria Elena Di Battista1, Giuseppe Battistella2, Patrizia Silvia Bisiacchi3, Enrico Di Giorgi4, 1Cognitive Impairment Center, Local Health Authority n. 9 of Treviso, Treviso, Italy; 2Service of Statistics and Epidemiology, Local Health Authority n. 9 of Treviso, Italy, Italy; 3General Psychology, University of Padua, Padua, Italy; 4Health Districts of Treviso, Local Health
P756
Poster Presentations: Monday, July 25, 2016
Authority n. 9 of Treviso, Italy, Italy. Contact e-mail: galluccimaurizio@ gmail.com Background: Mild Cognitive Impairment (MCI) is widely considered a phase of transition between normality and dementia. Most of the studies of conversion from MCI to dementia has focused on amnestic MCI (aMCI) that is considered a preclinical phase of Alzheimer Disease (AD). An important goal would be to identify the neuropsychological tools that better predict conversion from MCI to dementia. Methods: Fifty-five aMCI subjects of the Treviso Dementia (TREDEM) Registry, were considered. They underwent a neuropsychological assessment in the first visit and at follow-up. Cox proportional-hazard regression models were created to measure the association between the dependent variable (dementia’s diagnosis or MCI status maintainance) and indipendent variables (neuropsychological test scores at baseline). Results: The sample (28 women and 27 men; mean age 76,82 6 5,88 ys; education 7,62 6 3,99 ys) was observed for an average time of 2,17 6 1,25 ys. A Cox backward stepwise regression showed that Rey Auditiory Verbal Learning Test, Delayed Recall (RAVLT-DR) (p¼.041) and Semantic Verbal Fluency (SVF) (p¼.031) appear to be able to predict conversion to dementia. Age and education were significant, respectively as risk (Exp B¼1,116) and protective (Exp B¼0,81) factors. Conclusions: RAVLT-DR and SVF would appear as proper tools to predict the conversion from aMCI to Dementia. P2-311
OUTCOMES FROM ROUTINE COGNITIVE SCREENING IN A HEALTH CARE SYSTEM
Leah R. Hanson1,2, Terry R. Barclay1,2, Ann M. Werner2, Lauren O. Erickson2, Jean M. Crow1,2, Soo Borson3, Kamakshi Lakshminarayan4, Michael H. Rosenbloom1,2, 1HealthPartners Center for Memory and Aging, Saint Paul, MN, USA; 2HealthPartners Institute, Bloomington, MN, USA; 3University of Washington, Seattle, WA, USA; 4University of Minnesota, Minneapolis, MN, USA. Contact e-mail: [email protected] Background: Even with routine health care, dementia often goes undiagnosed until the moderate-severe stages. The potential benefits of cognitive screening in the asymptomatic population are unclear. HealthPartners has piloted the use of the Mini-Cog as a standardized screening tool for cognitive function in patients aged 65 and older. Methods: Patients screened within specialty or primary care clinics were identified. Data from the 18 months prior to screening and the 18 months following screening were collected from the electronic medical record and included the Mini-Cog score (MC, scored 0-5), demographics, interventions received, and measures of healthcare utilization. Two definitions of screening positive were tested for the Mini-Cog (score of < 3 and < 4). Data analysis consisted of Poisson regression and normal mixed effects regression. Results: The MC was administered in 1,166 patients (average 77 yr, 58% female). Rates of patients screening positive for cognitive impairment were 16% and 32% (MC score of < 3 and < 4, respectively). Following a positive screen, documentation of diagnostic interventions (i.e. imaging, neuropsychology) were generally low (<7%), though significantly higher than after negative screens. In the 18 months following a positive screen, patients were more likely to be diagnosed with dementia or mild cognitive impairment (14% vs. 3%, p<0.001) and to receive a prescription for a dementia medication (12 % vs. 2%, p<0.001) as compared to patients with a negative screen, regardless of cutoff score used. Patients screening positive had a significantly lower overall incidence rate of office visits (-5%) in the 18 months following screening as compared to the
prior 18 months, which was more prominently seen in patients screened in primary care (-23%). Incidence of emergency room visits remained the same and hospitalizations changed significantly but differently by screen site, with significantly lower incidence in primary care screens and higher incidence in specialty care. Conclusions: Screening was associated with increased recognition of previously undetected cognitive impairment and changes in healthcare utilization. Further studies are needed to better understand what work flows may influence clinicians actions and increase the diagnostic follow-up of a positive screen.
P2-312
PREDICTING ALZHEIMER’S DISEASE IN OLDER ADULTS WITH MILD COGNITIVE IMPAIRMENT USING NEUROPSYCHOLOGICAL MEASURES: A SYSTEMATIC REVIEW AND META-ANALYSIS
Sylvie Belleville1,2, Celine Fouquet3, Carol Hudon4,5, CIMA-Q Group, 1 Institut Universitaire de Geriatrie de Montreal, Montreal, QC, Canada; 2 Universite de Montreal, Montreal, QC, Canada; 3Institut Universitaire de Geriatrie de Montreal, Montreal, QC, Canada; 4Universite Laval, Quebec, QC, Canada; 5Institut Universitaire en Sante Mentale de Quebec, Quebec, QC, Canada. Contact e-mail: [email protected] Background: An increasing number of longitudinal studies are attempting to identify tests that differentiate between persons with mild cognitive impairment (MCI) who will progress to dementia and those who will remain stable. The aim of this systematic quantitative review was to identify neuropsychological tests and cognitive domains that best predict progression to dementia of the Alzheimer type (AD). This was done by systematically reviewing and meta-analyzing the data of longitudinal studies reporting sensitivity and specificity values for neuropsychological tests to identify individuals with MCI who will decline and progress to AD in the future. Methods: The study was conducted in accordance with the PRISMA and PICOS statements. Articles were searched using appropriate key words in PubMed, Cochrane, EMBASE, PsycINFO, and ISI Web of Knowledge. Their methodological quality was assessed using the STARDem standards as well as the QUADAS, PRISMA, and Cochrane statements. Sensitivity (correct identification of progressors) and specificity (correct rejection of nonprogressors) of individual neuropsychological tests were calculated, meta-analyzed, and summarized in Forest plots. We also reviewed the sensitivity/specificity of combined tests when available. Results: 4,979 articles were initially retrieved. After the exclusion of irrelevant and duplicate articles, 26 eligible studies were analyzed. They reported data from a total of 52 neuropsychological tests (13 cognitive domains) and the mean follow-up ranged from 1 to 5 years. Many of the individual tests showed a trade-off between specificity and sensitivity, as those with good specificity values were generally of low sensitivity, and vice versa. Tests measuring general cognition (e.g., CAMCOG, ACE) or associative memory showed relatively good sensitivity but low specificity. In turn, measures of cued recall, semantic memory and language, showed relatively good specificity but low sensitivity. Tests of episodic memory, particularly those measuring delayed recall, showed a good balance between sensitivity and specificity. Sensitivity and specificity were largely improved (often > 85%) when combining memory measures with a small set of other domains. Conclusions: Individual tests vary in their sensitivity/specificity ratio and few have an appropriate balance between sensitivity and specificity. Relying on a combination of neuropsychological measures is likely to be the best approach to identify future progressors.