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Comparison of cognitive screening measures for primary care
P370
Poster Presentations: P2
methodology research may reduce reporting bias. Empirical research evaluating effectiveness of new methods to increase signal detection holds important consequences for CTM. P2-305
DONEPEZIL FOR MEMORY DECLINE IN MILD COGNITIVE IMPAIRMENT: EFFICACY AND LIMITATIONS IN A SEVEN-YEAR FOLLOW-UP STUDY
Reiko Koide1, Kinjo Hikari2, Shinichi Shoji3, Akira Tamaoka4, 1University of Tsukuba, Tsukuba-Schi, Ibaraki-Ken, Japan; 2Otsuma Women’s University, Tama-Shi, Japan; 3Shironishi Hospital, Matsumoto-Shi, Nagano-Ken, Japan; 4University of Tsukuba, Tsukuba, Japan. Background: Donepezil hydrochloride (Aricept) is a selective acetylcholinesterase inhibitor for the treatment of Alzheimer’s disease (AD). However, the memory domains for which the agent is effective, especially in very early phase of the disease, have not been clarified. We observed patients with amnestic mild cognitive impairment (aMCI) for seven years to determine the efficacy and limitations of donepezil. Methods: Ten patients with aMCI were diagnosed on the basis of intact daily activity, normal Mini-Mental State Examination (MMSE) score, and deviated memory reduction (less than 85) on at least one index of the Wechsler Memory Scale Revised (WMS-R). Single photon emission tomography (SPECT) showed AD patterns in the Three-Dimensional Stereotactic Surface Projection (3DSSP) analysis. All patients received Aricept, 5 mg/day, with informed consent. The WMS-R and a set of spatial memory tests (SMT) we devised were administered at baseline and at months 6, 12, 36, 60, and 84. The SMT comprised two subtests: (a) a spatial source memory test, assessing the memory of the agent of an action (who acted) and the reality of an action (acted or imagined) using line drawings of furniture on small pieces of paper and a virtual room and (b) a line drawing furniture completion test, assessing the ability to organize spatial representations, in which patients were requested to insert an important part of a piece of furniture in the appropriate position. Both subtests assess cognitive ability to manipulate three-dimensional ideations underlying memory of a space. Results: At baseline, all patients showed one or more WMS-R index scores below 85 along with errors on SMT. At month 6, all patients scored WMS-R index scores higher than 85, and this improvement was preserved till month 84. However, the error on SMT remained in all patients throughout the study. Conclusions: Donepezil hydrochloride, prescribed early in the course of AD, improves general (verbal and visual) memory function, as assessed by a standardized memory test, and preserves it for a considerable period of time; however, it does not affect spatial memory function, which requires three-dimensional ideation. The memory impairment related to manipulation of spatial representations might be germane to AD. P2-306
COMPARISON OF COGNITIVE SCREENING MEASURES FOR PRIMARY CARE
Robert Kane1, David Loreck2, Beth Klingaman3, Sara Carney4, Amy Provan5, 1TATRC, Washington, District of Columbia, United States; 2 VA Maryland Health Care System, Baltimore, Baltimore, Maryland, United States; 3University of Maryland, College Park, Maryland, United States; 4 VA Maryland Health Care System, Baltimore, Maryland, United States; 5 Notre Dame of Maryland, Baltimore, Maryland, United States. Background: The incidence of dementia, development of new medications, and the Medicare requirement to incorporate dementia screening into yearly examinations underscore the need to develop efficient cognitive screening methods. We report findings from a study with the following objectives: 1) assess the percentage of outpatients diagnosed with disorders indicating cognitive impairment based on routine care, 2) assess the percentage of patients diagnosed with cognitive problems employing a pilot primary care (PC) screening program, 3) compare various screening instruments with respect to their sensitivity and specificity for detecting cognitive impairment, and 4) determine the number of patients identified during screening already diagnosed with a condition affecting cognition. Methods: Initial diagnoses were established via record review of patients age 65 and older. We then implemented a screening program within a PC clinic employing two mental status examinations (Mini-Mental Status Examination, MMSE; Blessed Orientation-
Memory-Concentration Test, BOMC) and two informant questionnaires (Functional Activities Questionnaire, FAQ; Symptom Screen for Dementia, SSD). Participants were classified as screening probable if they evidenced impairment on at least one mental status and one informant measure; possible if they evidenced impairment on either a mental status or informant measure, or negative. We computed the sensitivity and specificity of each instrument relative to these risk categories. Results: Record review of 4006 patients indicated 161 (4.01%) with a diagnosis indicative of cognitive impairment. Of 515 PC patients age 65 or older participating in the pilot, 23 had a chart diagnosis indicative of cognitive impairment: 16 screened probable, 6 possible, and 1 negative. Of 515 patients screened, 32 (6.2%) were probable, 98 (19%) possible, and 385 (74.8%) negative. The FAQ had the highest positive predictive value and best combined predictive values; SSD had the highest negative predictive value. The BOMC outperformed the MMSE. Conclusions: Results indicated that, compared with routine care, formal screening identifies a greater proportion of patients age 65 and older who appear to demonstrate cognitive change or where further evaluation of cognitive status is required. Results also suggest that questionnaires given to family members may be an efficient method to augment routine screening for cognitive changes in PC setting. Table 1 Sensitivity, Specificity, Positive Predictive Value (PPV), and Negative Predictive Value (NPV) for Screening Measures and Chart Review Measure
Sensitivity
Specificity
PPV
NPV
MMSE BOMC FAQ SSD Chart Review
75.0% 90.6% 71.9% 96.9% 50%
88.4% 94.4% 97.7% 94.2% 98.6%
30.0% 51.8% 67.6% 52.5% 69.6%
98.2% 99.3% 98.1% 99.8% 96.7%
P2-307
INTRAINDIVIDUAL VARIABILITY ACROSS NEUROPSYCHOLOGICAL TASKS IS ASSOCIATED WITH RISK OF ALZHEIMER’S DISEASE
Stuart MacDonald1, Paul Brewster1, Erika Laukka2, Laura Fratiglioni3, Lars B€ackman2, 1University of Victoria, Victoria, British Columbia, Canada; 2Karolinska Institutet, Stockholm, Sweden; 3ARC- Karolinska Institutet, Stockholm, Sweden. Background: Recent theorizing suggests that within-person variability, across trials of an individual task as well as across a neuropsychological task profile, is linked to cognitive function (Holzter et al., 2008; Hultsch et al., 2002). In the present study, we employ data from the Kungsholmen Project (KP), a Swedish population-based longitudinal study, to evaluate whether across-task within-person variability estimates are linked to increased dementia risk independent of select confounds. Methods: Dispersion is operationalized as intraindividual variability across key neuropsychological tasks, computed as the intraindividual standard deviation (ISD) for each individual independent of mean age group differences in performance. Neuropsychological tests known to differentiate cognitively intact from impaired groups were selected, including episodic recall and recognition, block design, category and letter fluency, and Trailmaking. A total of 234 controls and 67 Alzheimer Disease (AD) cases were evaluated at cross-section. Results: Increased variability across the neuropsychological profile was clearly linked to increased risk for AD. Individuals with AD exhibited higher dispersion values, reflecting relatively uneven performance profiles across the neuropsychological test battery. Independent of age and years of education, a per-unit increase in ISD was associated with a 12.3% increase of AD. Notably, restricting the dispersion calculations to episodic memory measures varying in level of support (recall vs. recognition, free vs. cued recall, etc) did not facilitate detection of those at increased risk of AD. Conclusions: Findings will be discussed in terms of the implications of dispersion for supplementing existing neuropsychological batteries, and for improving sensitivity to detect those at risk of AD. We are currently exploring the longitudinal link between changes in dispersion and dementia risk across as many as 12 years of measurement in the KP.
Poster Presentations: P2
methodology research may reduce reporting bias. Empirical research evaluating effectiveness of new methods to increase signal detection holds important consequences for CTM. P2-305
DONEPEZIL FOR MEMORY DECLINE IN MILD COGNITIVE IMPAIRMENT: EFFICACY AND LIMITATIONS IN A SEVEN-YEAR FOLLOW-UP STUDY
Reiko Koide1, Kinjo Hikari2, Shinichi Shoji3, Akira Tamaoka4, 1University of Tsukuba, Tsukuba-Schi, Ibaraki-Ken, Japan; 2Otsuma Women’s University, Tama-Shi, Japan; 3Shironishi Hospital, Matsumoto-Shi, Nagano-Ken, Japan; 4University of Tsukuba, Tsukuba, Japan. Background: Donepezil hydrochloride (Aricept) is a selective acetylcholinesterase inhibitor for the treatment of Alzheimer’s disease (AD). However, the memory domains for which the agent is effective, especially in very early phase of the disease, have not been clarified. We observed patients with amnestic mild cognitive impairment (aMCI) for seven years to determine the efficacy and limitations of donepezil. Methods: Ten patients with aMCI were diagnosed on the basis of intact daily activity, normal Mini-Mental State Examination (MMSE) score, and deviated memory reduction (less than 85) on at least one index of the Wechsler Memory Scale Revised (WMS-R). Single photon emission tomography (SPECT) showed AD patterns in the Three-Dimensional Stereotactic Surface Projection (3DSSP) analysis. All patients received Aricept, 5 mg/day, with informed consent. The WMS-R and a set of spatial memory tests (SMT) we devised were administered at baseline and at months 6, 12, 36, 60, and 84. The SMT comprised two subtests: (a) a spatial source memory test, assessing the memory of the agent of an action (who acted) and the reality of an action (acted or imagined) using line drawings of furniture on small pieces of paper and a virtual room and (b) a line drawing furniture completion test, assessing the ability to organize spatial representations, in which patients were requested to insert an important part of a piece of furniture in the appropriate position. Both subtests assess cognitive ability to manipulate three-dimensional ideations underlying memory of a space. Results: At baseline, all patients showed one or more WMS-R index scores below 85 along with errors on SMT. At month 6, all patients scored WMS-R index scores higher than 85, and this improvement was preserved till month 84. However, the error on SMT remained in all patients throughout the study. Conclusions: Donepezil hydrochloride, prescribed early in the course of AD, improves general (verbal and visual) memory function, as assessed by a standardized memory test, and preserves it for a considerable period of time; however, it does not affect spatial memory function, which requires three-dimensional ideation. The memory impairment related to manipulation of spatial representations might be germane to AD. P2-306
COMPARISON OF COGNITIVE SCREENING MEASURES FOR PRIMARY CARE
Robert Kane1, David Loreck2, Beth Klingaman3, Sara Carney4, Amy Provan5, 1TATRC, Washington, District of Columbia, United States; 2 VA Maryland Health Care System, Baltimore, Baltimore, Maryland, United States; 3University of Maryland, College Park, Maryland, United States; 4 VA Maryland Health Care System, Baltimore, Maryland, United States; 5 Notre Dame of Maryland, Baltimore, Maryland, United States. Background: The incidence of dementia, development of new medications, and the Medicare requirement to incorporate dementia screening into yearly examinations underscore the need to develop efficient cognitive screening methods. We report findings from a study with the following objectives: 1) assess the percentage of outpatients diagnosed with disorders indicating cognitive impairment based on routine care, 2) assess the percentage of patients diagnosed with cognitive problems employing a pilot primary care (PC) screening program, 3) compare various screening instruments with respect to their sensitivity and specificity for detecting cognitive impairment, and 4) determine the number of patients identified during screening already diagnosed with a condition affecting cognition. Methods: Initial diagnoses were established via record review of patients age 65 and older. We then implemented a screening program within a PC clinic employing two mental status examinations (Mini-Mental Status Examination, MMSE; Blessed Orientation-
Memory-Concentration Test, BOMC) and two informant questionnaires (Functional Activities Questionnaire, FAQ; Symptom Screen for Dementia, SSD). Participants were classified as screening probable if they evidenced impairment on at least one mental status and one informant measure; possible if they evidenced impairment on either a mental status or informant measure, or negative. We computed the sensitivity and specificity of each instrument relative to these risk categories. Results: Record review of 4006 patients indicated 161 (4.01%) with a diagnosis indicative of cognitive impairment. Of 515 PC patients age 65 or older participating in the pilot, 23 had a chart diagnosis indicative of cognitive impairment: 16 screened probable, 6 possible, and 1 negative. Of 515 patients screened, 32 (6.2%) were probable, 98 (19%) possible, and 385 (74.8%) negative. The FAQ had the highest positive predictive value and best combined predictive values; SSD had the highest negative predictive value. The BOMC outperformed the MMSE. Conclusions: Results indicated that, compared with routine care, formal screening identifies a greater proportion of patients age 65 and older who appear to demonstrate cognitive change or where further evaluation of cognitive status is required. Results also suggest that questionnaires given to family members may be an efficient method to augment routine screening for cognitive changes in PC setting. Table 1 Sensitivity, Specificity, Positive Predictive Value (PPV), and Negative Predictive Value (NPV) for Screening Measures and Chart Review Measure
Sensitivity
Specificity
PPV
NPV
MMSE BOMC FAQ SSD Chart Review
75.0% 90.6% 71.9% 96.9% 50%
88.4% 94.4% 97.7% 94.2% 98.6%
30.0% 51.8% 67.6% 52.5% 69.6%
98.2% 99.3% 98.1% 99.8% 96.7%
P2-307
INTRAINDIVIDUAL VARIABILITY ACROSS NEUROPSYCHOLOGICAL TASKS IS ASSOCIATED WITH RISK OF ALZHEIMER’S DISEASE
Stuart MacDonald1, Paul Brewster1, Erika Laukka2, Laura Fratiglioni3, Lars B€ackman2, 1University of Victoria, Victoria, British Columbia, Canada; 2Karolinska Institutet, Stockholm, Sweden; 3ARC- Karolinska Institutet, Stockholm, Sweden. Background: Recent theorizing suggests that within-person variability, across trials of an individual task as well as across a neuropsychological task profile, is linked to cognitive function (Holzter et al., 2008; Hultsch et al., 2002). In the present study, we employ data from the Kungsholmen Project (KP), a Swedish population-based longitudinal study, to evaluate whether across-task within-person variability estimates are linked to increased dementia risk independent of select confounds. Methods: Dispersion is operationalized as intraindividual variability across key neuropsychological tasks, computed as the intraindividual standard deviation (ISD) for each individual independent of mean age group differences in performance. Neuropsychological tests known to differentiate cognitively intact from impaired groups were selected, including episodic recall and recognition, block design, category and letter fluency, and Trailmaking. A total of 234 controls and 67 Alzheimer Disease (AD) cases were evaluated at cross-section. Results: Increased variability across the neuropsychological profile was clearly linked to increased risk for AD. Individuals with AD exhibited higher dispersion values, reflecting relatively uneven performance profiles across the neuropsychological test battery. Independent of age and years of education, a per-unit increase in ISD was associated with a 12.3% increase of AD. Notably, restricting the dispersion calculations to episodic memory measures varying in level of support (recall vs. recognition, free vs. cued recall, etc) did not facilitate detection of those at increased risk of AD. Conclusions: Findings will be discussed in terms of the implications of dispersion for supplementing existing neuropsychological batteries, and for improving sensitivity to detect those at risk of AD. We are currently exploring the longitudinal link between changes in dispersion and dementia risk across as many as 12 years of measurement in the KP.