- Email: [email protected]
Assessing the capacity of patients with dementia to provide informed consent to participate in research: How important is memory?
Poster Presentations P3 show a similar pattern of performance on measures of verbal fluency. Methods: Eighty-one aMCI, 54 mild AD, and 97 normal control (NC) subjects were identified from the database of the Easton Center for Alzheimer’s Disease Research. These subjects underwent formal neuropsychological assessment that included verbal fluency tasks based on phonemic (generating words with specified letters of the alphabet) and semantic/categorical (generating words within a specified category, e.g., animals) criteria. Raw and standardized scores were compared between aMCI, AD, and NC groups using one-way analysis of covariance (ANCOVA), controlling for age and education. In addition, a difference score was calculated between semantic and phonemic fluency trials to examine the association between semantic and phonemic fluency. Results: Phonemic and semantic verbal fluency raw and standardized scores were significantly lower in the AD group than both aMCI and NC groups while the aMCI group produced scores that were intermediate to that of the other two groups. In contrast, the semantic-phonemic difference score was significantly higher in the NC group than the aMCI and AD groups, but the latter two groups did not differ significantly on this measure. On average, the NC group produced 6.4 more words on semantic fluency than phonemic fluency while the aMCI and AD groups produced an average of 2 and 1.75 more words, respectively, with semantic than phonemic cues. Conclusions: The fewer words produced by aMCI and AD patients on semantic fluency relative to phonemic fluency suggest greater impairment in semantic knowledge and retrieval. This has been well documented in AD but the similarity in pattern of performance suggests that similar neuropathological changes may also be present in aMCI.
P3-155
ASSESSING THE CAPACITY OF PATIENTS WITH DEMENTIA TO PROVIDE INFORMED CONSENT TO PARTICIPATE IN RESEARCH: HOW IMPORTANT IS MEMORY?
Jane F. Sachs1, Jacqueline Lee1, Zachary Zugin1, Cynthia M. Carlsson1,2, Hanna Blazel1, Tamara Markgraf1, Sanjay Asthana1,2, Carey E. Gleason1,2, 1 University of Wisconsin, School of Medicine and Public Health, Madison, WI, USA; 2Geriatric Research, Education and Clinical Center (GRECC) of the Wm. S. Middleton Memorial VA Hospital, Madison, WI, USA. Contact e-mail: [email protected] Background: Enrolling dementia patients into clinical research necessitates an assessment of their capacity to provide informed consent. While practices vary, the American Psychological Association and the American Bar Association provide guidelines for assessment based on the Appelbaum-Grisso model. It emphasizes an understanding of disclosed information, appreciation of its significance, and the ability to reason and express choice based on that information. The few available formalized assessment tools gauge capacity based on recollection of study specific details, like possible side effects. This is highly problematic for subjects with dementia. Methods: In an attempt to structure the clinical assessment of capacity to participate in research, we developed four questions to assess a dementia patient’s ability to understand, appreciate, reason, and express their decision. We intentionally minimize the role of memory by permitting the repetition of key details discussed in the consent form, especially while assessing their ability to appreciate participation risks. Results: The evaluation process ensures that potential subjects 1) understand that participation is optional, 2) appreciate that participation involves inherent risks, 3) can demonstrate the ability to reason, and 4) express a willingness to participate. Typically, patients do not remember the specific risks entailed in study participation. Once reminded, however, they are often able to express their opinion as to whether they judge the risks as reasonable or not. Conclusions: Legally, capacity necessitates that a party understands the nature and consequence of what is happening at the time that consent is given. While the law does not clarify whether the party must be capable of remembering specifics, the instruments used to assess capacity to consent often require recollection of study details. The researcher has a duty to determine that a patient has the capacity to provide informed consent
S495
when entering a research study. However, the protection of autonomy is equally important, and current practices may be overly restrictive for patients with dementia. We propose a method of assessing decisional capacity that is less reliant on intact memory, and instead requires a demonstrated understanding of what it means to be in research and an appreciation of the risks involved therein. P3-156
COGNITION AND BRAIN STRUCTURE IN GERSTMANN-STRAUSSLER-SCHEINKER DISEASE (PRNP F198S)
Frederick W. Unverzagt1, Martin R. Farlow1, Sujuan Gao1, Andrew J. Saykin1, Jill R. Murrell1, Shannon L. Risacher1, Kathleen A. Lane1, John D. West1, Brandy R. Matthews1, Pedro Piccardo2, Leticia Miravalle1, Ruben G. Vidal1, Bernardino Ghetti1, 1Indiana University School of Medicine, Indianapolis, IN, USA; 2FDA, Silver Spring, MD, USA. Contact e-mail: [email protected] Background: We examined the relationship of cognitive, motor, and brain structure changes to mutation status in a large kindred at risk for Gerstmann-Straussler-Scheinker disease (GSS), an autosomal dominant prion disease known to have early neuropathological change in the cerebellum. Methods: Sixty-seven family members from the Indiana GSS Kindred (PRNP F198S) were clinically assessed and had PRNP sequenced in the Indiana Alzheimer Disease Center. Standard clinical assessment and consensus diagnosis procedures were used resulting in nine subjects diagnosed as demented with all having the PRNP F198S mutation (D+M+), 22 were non-demented but carried the mutation (D-M+), and 36 were non-demented and free of the mutation (D-M-). MRI was obtained on 14 subjects and analyzed via Freesurfer4 for cortical thickness and volume. Results: The groups differed significantly in age and there were trends for differences in proportion female and years of education. After controlling for age, gender, and education, the D+M+ group had significantly worse digit span, prose recall, figural recall, and verbal fluency with a trend for worse block design and finger tapping compared to the D-M- group. The D-M+ group had significantly worse finger tapping speed and list learning efficiency with a trend for worse prose recall and grooved pegboard time compared to the D-M- group. The D-M- group tended to have greater mean bilateral entorhinal cortex thickness and cerebral white matter and cerebellar cortex volume than the M+ groups. Conclusions: Manual motor and verbal memory dysfunction appear to be early neuropsychological changes in the Indiana kindred with GSS (PRNP F198S). These impairments may relate to early structural change in the cerebellum and medial temporal lobes in this disease. P3-157
ROBUST NORMS FOR THE ADC-UDS COGNITIVE TEST BATTERY
Susan De Santi1,2, Elizabeth Pirraglia2, Steven H. Ferris2,3, John C. Morris4, Sandra Weintraub5, Nancy Johnson5, 1MedAvante, Inc., Hamilton, NJ, USA; 2 New York University Langone Medical Center, New York, NY, USA; 3The Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USA; 4 Washington University, St. Louis, MO, USA; 5Northwestern University, Evanston, IL, USA. Contact e-mail: [email protected] Background: Robust norms developed on longitudinally stable normal individuals improve identification of future cognitive decline in healthy individuals. The neuropsychological battery from the Uniform Data Set (UDS) of the NIA Alzheimer’s Disease Centers (ADC) is used to assess cognitive performance by all ADCs. Robust norms for this test battery would provide more sensitive reference data for identifying cognitive impairment in the ADC population. We developed Robust norms for the UDS cognitive battery using longitudinally stable normal individuals and determined the utility of these norms for identifying decline to MCI or AD. Methods: We retrospectively examined UDS data from 375 normal individuals from Northwestern University (n ¼ 91), Washington University (n ¼ 150) and NYU (n ¼ 131) who were normal at the first administration of the UDS cognitive battery and had at least 2 administrations of this examination.
P3-155
ASSESSING THE CAPACITY OF PATIENTS WITH DEMENTIA TO PROVIDE INFORMED CONSENT TO PARTICIPATE IN RESEARCH: HOW IMPORTANT IS MEMORY?
Jane F. Sachs1, Jacqueline Lee1, Zachary Zugin1, Cynthia M. Carlsson1,2, Hanna Blazel1, Tamara Markgraf1, Sanjay Asthana1,2, Carey E. Gleason1,2, 1 University of Wisconsin, School of Medicine and Public Health, Madison, WI, USA; 2Geriatric Research, Education and Clinical Center (GRECC) of the Wm. S. Middleton Memorial VA Hospital, Madison, WI, USA. Contact e-mail: [email protected] Background: Enrolling dementia patients into clinical research necessitates an assessment of their capacity to provide informed consent. While practices vary, the American Psychological Association and the American Bar Association provide guidelines for assessment based on the Appelbaum-Grisso model. It emphasizes an understanding of disclosed information, appreciation of its significance, and the ability to reason and express choice based on that information. The few available formalized assessment tools gauge capacity based on recollection of study specific details, like possible side effects. This is highly problematic for subjects with dementia. Methods: In an attempt to structure the clinical assessment of capacity to participate in research, we developed four questions to assess a dementia patient’s ability to understand, appreciate, reason, and express their decision. We intentionally minimize the role of memory by permitting the repetition of key details discussed in the consent form, especially while assessing their ability to appreciate participation risks. Results: The evaluation process ensures that potential subjects 1) understand that participation is optional, 2) appreciate that participation involves inherent risks, 3) can demonstrate the ability to reason, and 4) express a willingness to participate. Typically, patients do not remember the specific risks entailed in study participation. Once reminded, however, they are often able to express their opinion as to whether they judge the risks as reasonable or not. Conclusions: Legally, capacity necessitates that a party understands the nature and consequence of what is happening at the time that consent is given. While the law does not clarify whether the party must be capable of remembering specifics, the instruments used to assess capacity to consent often require recollection of study details. The researcher has a duty to determine that a patient has the capacity to provide informed consent
S495
when entering a research study. However, the protection of autonomy is equally important, and current practices may be overly restrictive for patients with dementia. We propose a method of assessing decisional capacity that is less reliant on intact memory, and instead requires a demonstrated understanding of what it means to be in research and an appreciation of the risks involved therein. P3-156
COGNITION AND BRAIN STRUCTURE IN GERSTMANN-STRAUSSLER-SCHEINKER DISEASE (PRNP F198S)
Frederick W. Unverzagt1, Martin R. Farlow1, Sujuan Gao1, Andrew J. Saykin1, Jill R. Murrell1, Shannon L. Risacher1, Kathleen A. Lane1, John D. West1, Brandy R. Matthews1, Pedro Piccardo2, Leticia Miravalle1, Ruben G. Vidal1, Bernardino Ghetti1, 1Indiana University School of Medicine, Indianapolis, IN, USA; 2FDA, Silver Spring, MD, USA. Contact e-mail: [email protected] Background: We examined the relationship of cognitive, motor, and brain structure changes to mutation status in a large kindred at risk for Gerstmann-Straussler-Scheinker disease (GSS), an autosomal dominant prion disease known to have early neuropathological change in the cerebellum. Methods: Sixty-seven family members from the Indiana GSS Kindred (PRNP F198S) were clinically assessed and had PRNP sequenced in the Indiana Alzheimer Disease Center. Standard clinical assessment and consensus diagnosis procedures were used resulting in nine subjects diagnosed as demented with all having the PRNP F198S mutation (D+M+), 22 were non-demented but carried the mutation (D-M+), and 36 were non-demented and free of the mutation (D-M-). MRI was obtained on 14 subjects and analyzed via Freesurfer4 for cortical thickness and volume. Results: The groups differed significantly in age and there were trends for differences in proportion female and years of education. After controlling for age, gender, and education, the D+M+ group had significantly worse digit span, prose recall, figural recall, and verbal fluency with a trend for worse block design and finger tapping compared to the D-M- group. The D-M+ group had significantly worse finger tapping speed and list learning efficiency with a trend for worse prose recall and grooved pegboard time compared to the D-M- group. The D-M- group tended to have greater mean bilateral entorhinal cortex thickness and cerebral white matter and cerebellar cortex volume than the M+ groups. Conclusions: Manual motor and verbal memory dysfunction appear to be early neuropsychological changes in the Indiana kindred with GSS (PRNP F198S). These impairments may relate to early structural change in the cerebellum and medial temporal lobes in this disease. P3-157
ROBUST NORMS FOR THE ADC-UDS COGNITIVE TEST BATTERY
Susan De Santi1,2, Elizabeth Pirraglia2, Steven H. Ferris2,3, John C. Morris4, Sandra Weintraub5, Nancy Johnson5, 1MedAvante, Inc., Hamilton, NJ, USA; 2 New York University Langone Medical Center, New York, NY, USA; 3The Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USA; 4 Washington University, St. Louis, MO, USA; 5Northwestern University, Evanston, IL, USA. Contact e-mail: [email protected] Background: Robust norms developed on longitudinally stable normal individuals improve identification of future cognitive decline in healthy individuals. The neuropsychological battery from the Uniform Data Set (UDS) of the NIA Alzheimer’s Disease Centers (ADC) is used to assess cognitive performance by all ADCs. Robust norms for this test battery would provide more sensitive reference data for identifying cognitive impairment in the ADC population. We developed Robust norms for the UDS cognitive battery using longitudinally stable normal individuals and determined the utility of these norms for identifying decline to MCI or AD. Methods: We retrospectively examined UDS data from 375 normal individuals from Northwestern University (n ¼ 91), Washington University (n ¼ 150) and NYU (n ¼ 131) who were normal at the first administration of the UDS cognitive battery and had at least 2 administrations of this examination.