Jason Karlawish | University of Pennsylvania (original) (raw)

Papers by Jason Karlawish

Journal of Palliative Medicine, 2002

Improvements in end-of-life care will require an active program of research, and this research wi... more Improvements in end-of-life care will require an active program of research, and this research will need to involve patients in hospice. However, it is not known whether hospices are prepared to participate in research, nor is it known what barriers may prevent hospices from becoming involved in research. This nationwide telephone survey was conducted with a random sample of hospice organizations taken from a national database. Questions elicited the research activities in which hospices are involved, the resources that hospices have available for the ethical review of research, and perceived barriers to research participation. Of 88 hospices identified, 17 (19%) reported that they had participated in research in the past year. Hospices that participated in research were more likely to be urban, affiliated with an academic institution, and were more likely to have an inpatient unit. Hospices cited several barriers to research participation, including time commitments, staffing resources, ethical concerns, and burdens to patients and families. The most important concern was lack of staffing resources. Hospices indicated that they would be most willing to support research regarding pain management and timing of referral to hospice.

Health education & behavior : the official publication of the Society for Public Health Education, 2014

Financial incentives and peer networks could be delivered through eHealth technologies to encoura... more Financial incentives and peer networks could be delivered through eHealth technologies to encourage older adults to walk more. We conducted a 24-week randomized trial in which 92 older adults with a computer and Internet access received a pedometer, daily walking goals, and weekly feedback on goal achievement. Participants were randomized to weekly feedback only (Comparison), entry into a lottery with potential to earn up to $200 each week walking goals were met (Financial Incentive), linkage to four other participants through an online message board (Peer Network), or both interventions (Combined). Main outcomes were the proportion of days walking goals were met during the 16-week intervention and 8-week follow-up. We conducted a content analysis of messages posted by Peer Network and Combined arm participants. During the 16-week intervention, there were no differences in the proportion of days walking goals were met in the Financial Incentive (39.7%; p = .78), Peer Network (24.9%;...

LDI issue brief, 2008

This presidential election year reminds us of the importance of each vote and of the integrity of... more This presidential election year reminds us of the importance of each vote and of the integrity of the electoral process. Recent elections have been decided by very narrow margins. In this context, the voting rights and capacity of persons with dementia warrant attention. About 4.5 million Americans currently live with dementia. Whether these citizens should vote raises a host of ethical, legal, and practical issues. At what point does someone lose the capacity to vote, and who decides? What kinds of assistance should these voters get, and who should provide it? And how can the voting rights of residents in long-term care facilities be protected?

Alzheimers & Dementia, 2011

Memory awareness in early Alzheimer's disease (AD) influences capacity to provide informed consen... more Memory awareness in early Alzheimer's disease (AD) influences capacity to provide informed consent for a memory treatment. This study investigated the extent to which aspects of memory awareness influence everyday decision-making capacity about medication management in AD. 42 participants with mild AD and 50 healthy elders underwent clinical ratings of memory awareness, metamemory testing, and an interview of everyday decision-making capacity regarding medication management. 45% of AD subjects were classified as aware (AAD) and 55% as unaware (UAD) based on clinical ratings and supported by metamemory testing (P = .015). Capacity was impaired in each of the AD groups as compared to the healthy elders F(2, 67) = 17.63, UAD, P < .01; AAD, P = .01). Within the AD group, capacity correlated selectively with awareness as measured with clinical ratings (r = −.41, P = .007) but not objective metamemory testing (r = −.10, P = .60 ). Appreciation scores were lower in UAD as compared with AAD F(1, 35) = 8.36, P = .007. Unawareness of memory loss should heighten clinicians' concern about everyday decision-making capacity in AD.

Neurology, Jan 11, 2015

Prevention trials for neurodegenerative diseases use genetic or other risk marker tests to select... more Prevention trials for neurodegenerative diseases use genetic or other risk marker tests to select participants but there is concern that this could involve coercive disclosure of unwanted information. This has led some trials to use blinded enrollment (participants are tested but not told of their risk marker status). We examined the ethics of blinded vs transparent enrollment using well-established criteria for assessing the ethics of clinical research. Normative analysis applying 4 key ethical criteria-favorable risk-benefit ratio, informed consent, fair subject selection, and scientific validity-to blinded vs transparent enrollment, using current evidence and state of Alzheimer disease (AD) and other prevention trials. Current evidence on the psychosocial impact of risk marker disclosure and considerations of scientific benefit do not support an obligation to use blinded enrollment in prevention trials. Nor does transparent enrollment coerce or involve undue influence of potentia...

Neuropsychology, 2014

Metamemory, or knowledge of one&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s memory ... more Metamemory, or knowledge of one&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s memory abilities, is often impaired in individuals with Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease (AD), although the basis of this metacognitive deficit has not been fully articulated. Behavioral and imaging studies have produced conflicting evidence regarding the extent to which specific cognitive domains (i.e., executive function; memory) and brain regions contribute to memory awareness. The primary aim of this study was to disentangle the cognitive correlates of metamemory in AD by examining the relatedness of objective metamemory performance to cognitive tasks grouped by domain (executive function or memory) as well as by preferential hemispheric reliance defined by task modality (verbal or nonverbal). Eighty-nine participants with mild AD recruited at Columbia University Medical Center and the University of Pennsylvania underwent objective metamemory and cognitive testing. Partial correlations were used to assess the relationship between metamemory and four cognitive variables, adjusted for recruitment site. The significant correlates of metamemory included nonverbal fluency (r = .27, p = .02) and nonverbal memory (r = .24, p = .04). Our findings suggest that objectively measured metamemory in a large sample of individuals with mild AD is selectively related to a set of interdomain nonverbal tasks. The association between metamemory and the nonverbal tasks may implicate a shared reliance on a right-sided cognitive network that spans frontal and temporal regions.

Neurobiology of Aging - NEUROBIOL AGING, 2004

Background: This presentation reports on several trans-cultural/llnguistic studies with the Alzhe... more Background: This presentation reports on several trans-cultural/llnguistic studies with the Alzheimer's Quick Test (AQT). AQT Color-Form Naming (AQT-CF) is currently used as part of a neurnpsychological testing in a longitudinal study of adults with normal cognitive functioning and with mild-to-moderate AD (University Hospital MAS, Sweden). It has been accepted for inclusion in the EU Consortium Centre studies of Alzheimer's Disease (DESCRIPA). Objective(s): The purpose was to establish if AQT naming times (sec.) would differentiate between adults from different language and cultural backgrounds with and without cognitive impairments and to compare discriminant values of AQT with MMSE scores. Methods:

New England Journal of Medicine, 2012

Nature Genetics, 2011

A sonnen 95 , salvatore spina 63 , Robert A stern 31 , Rudolph e tanzi 67 , John Q trojanowski 6 ... more A sonnen 95 , salvatore spina 63 , Robert A stern 31 , Rudolph e tanzi 67 , John Q trojanowski 6 , Juan c troncoso 96 , Vivianna m Van deerlin 6 , Harry V Vinters 49,97 , Jean Paul Vonsattel 98 , sandra weintraub 85,86 , kathleen A welsh-Bohmer 41,99 , Jennifer williamson 70 , Randall l woltjer 100 , laura B cantwell 6 , Beth A dombroski 6 , duane Beekly 101 , kathryn l lunetta 2 , eden R martin 1,5 , m Ilyas kamboh 30,79 , Andrew J saykin 54,102 , eric m Reiman 28,103-105 , david A Bennett 22,106 , John c morris 42,107 , thomas J montine 95 , Alison m goate 23 , deborah Blacker 108,109 , debby w tsuang 91 , Hakon Hakonarson 110 , walter A kukull 111 , tatiana m Foroud 54 , Jonathan l Haines 112,113 , Richard mayeux 70,114 , margaret A Pericak-Vance 1,5 , lindsay A Farrer 2-4,31,32 & gerard d schellenberg 6

International Journal of Geriatric Psychiatry, 2007

Objective Depression occurs frequently in patients with both Alzheimer's disease (AD) and Parkins... more Objective Depression occurs frequently in patients with both Alzheimer's disease (AD) and Parkinson's disease (PD), but there has been little comparison of depression symptoms in the two populations. Method The 15-item Geriatric Depression Scale (GDS-15) was administered as a depression screening instrument to 232 AD patients and 266 PD specialty care patients with at most mild dementia. Logistic regression models were used to determine disease-specific associations with individual GDS-15 items, and factor analysis was used to assess GDS-15 factor structure in the two populations. Results Controlling for total GDS-15 score and other covariates, AD patients reported more dissatisfaction with life ( p ¼ 0.03) and memory problems ( p < 0.001), while PD patients reported more fearfulness ( p ¼ 0.01), helplessness ( p < 0.01), a preference to stay at home ( p ¼ 0.02), and diminished energy ( p < 0.01). Three factors were generated in PD (explaining 55% of the total variance) and five in AD (explaining 59% of the total variance), and the two main factors generated in both populations related primarily to unhappiness and negative thoughts. Conclusions The factor structure of the GDS-15 is similar in AD and PD patients with at most mild stage dementia, but between-group differences on 6 of the GDS-15 items suggests the non-specificity of certain items in the two populations.

Alzheimer's & Dementia, 2006

Balancing benefits and risks in the development of treatments for Alzheimer's disease is challeng... more Balancing benefits and risks in the development of treatments for Alzheimer's disease is challenging given the nature of the disease but critically important to ensure effective treatments are available. Drawing on a diverse panel of scientists, regulators, caregivers, patients and advocates convened by the Alzheimer's Association, insights are offered into benefit/risk assessment, decision-making, regulatory and societal factors affecting clinical trials on AD. Several policy solutions are offered to improve the drug testing, review and approval process.

Alzheimer's & Dementia, 2006

Acta Neuropathologica, 2010

Altered levels of cerebrospinal fluid (CSF) peptides related to Alzheimer's disease (AD) are asso... more Altered levels of cerebrospinal fluid (CSF) peptides related to Alzheimer's disease (AD) are associated with pathologic AD diagnosis, although cognitively normal subjects can also have abnormal levels of these AD biomarkers. To identify novel CSF biomarkers that distinguish pathologically confirmed AD from cognitively normal subjects and patients with other neurodegenerative disorders, we collected antemortem CSF samples from 66 AD patients and 25 patients with other neurodegenerative dementias followed longitudinally to neuropathologic confirmation, plus CSF from 33 cognitively normal subjects. We measured levels of 151 novel analytes via a targeted multiplex panel enriched in cytokines, chemokines and growth factors, as well as established AD CSF biomarkers (levels of Aβ42, tau and p-tau 181 ). Two categories of biomarkers were identified: (1) analytes that specifically distinguished AD (especially CSF Aβ42 levels) from cognitively normal subjects and other disorders; and (2) analytes altered in multiple diseases (NrCAM, PDGF, C3, IL-1α), but not in cognitively normal subjects. A multiprong analytical approach showed AD patients were best distinguished from non-AD cases (including cognitively normal subjects and patients with other neurodegenerative disorders) by a combination of traditional AD biomarkers and novel multiplex biomarkers. Six novel biomarkers (C3, CgA, IL-1α, I-309, NrCAM and VEGF) were correlated with the severity of cognitive impairment at CSF collection, and altered levels of IL-1α and TECK associated with subsequent cognitive decline in 38 longitudinally followed subjects with mild cognitive impairment. In summary, our targeted proteomic screen revealed novel CSF biomarkers that can improve the distinction between AD and non-AD cases by established biomarkers alone.

Journal of pain and symptom management, 2003

This paper examines the conditions that describe when it is appropriate to conduct research that ... more This paper examines the conditions that describe when it is appropriate to conduct research that enrolls a subject near the end-of-life who cannot provide an informed consent. Specifically, it describes conditions that justify when it is acceptable to expose a person to the risks, burdens or discomforts of an intervention that is not intended to benefit that person but to produce generalizable knowledge that will benefit other people. These conditions are: (1) acceptable research risks, (2) proxy decision making, (3) subject assent and dissent, and (4) subject advance consent.

The New England journal of medicine, Jan 3, 2003

... 33. Freedman B . Scientific value and validity as ethical requirements for research: a propos... more ... 33. Freedman B . Scientific value and validity as ethical requirements for research: a proposed explication. IRB 1987;9:7-10 CrossRef | Medline. 34. ... 36. National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research . ...

LDI issue brief, 2002

About four million Americans currently live with Alzheimer's disease (AD) or related forms of... more About four million Americans currently live with Alzheimer's disease (AD) or related forms of dementia. Because the disease process impairs language, insight, and judgment, family members become "caregivers." These caregivers, either in part or in full, often make decisions on patients' behalf. This Issue Brief summarizes a series of studies that describe how caregivers make decisions for AD patients, and caregiver perspectives on the quality of life for relatives with AD.

To explore the factors that patients with malignant and nonmalignant pain consider when deciding ... more To explore the factors that patients with malignant and nonmalignant pain consider when deciding whether to enroll in pain research studies, determine whether their views are different, and determine whether willingness to enroll in research is associated with pain severity, semistructured interviews were conducted with 80 patients (cancer pain: n ϭ 40; chronic nonmalignant pain: n ϭ 40). The risks and potential benefits that were important to patients with cancer were the same as those that were important to patients with chronic pain. Willingness to enroll in research was associated with pain severity (Spearman ϭ 0.33; P ϭ 0.041) in patients with chronic pain, but not in patients with cancer pain. Patients with cancer pain do not have different concerns than chronic pain patients do. Although chronic pain patients' willingness to enroll in research was related to pain severity and a desire for better pain management, cancer patients' willingness to enroll was not.

Objective-To determine whether participants with mild cognitive impairment (MCI) differ from cogn... more Objective-To determine whether participants with mild cognitive impairment (MCI) differ from cognitively normal (NC) older adults on traditional and novel informant-based measures of activities of daily living (ADL) and to identify cognitive correlates of ADLs among participants with MCI.

Alzheimer's & Dementia, 2014

The objective of this study was to develop a process to maximize the safety and effectiveness of ... more The objective of this study was to develop a process to maximize the safety and effectiveness of disclosing Positron Emission Tomography (PET) amyloid imaging results to cognitively normal older adults participating in Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease secondary prevention studies such as the Anti-Amyloid Treatment in Asymptomatic Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s Disease (A4) Study. Using a modified Delphi Method to develop consensus on best practices, we gathered and analyzed data over three rounds from experts in two relevant fields: informed consent for genetic testing or human amyloid imaging. Experts reached consensus on (1) text for a brochure that describes amyloid imaging to a person who is considering whether to undergo such imaging in the context of a clinical trial, and (2) a process for amyloid PET result disclosure within such trials. Recommendations included: During consent, potential participants should complete an educational session, where they receive verbal and written information covering what is known and unknown about amyloid imaging, including possible results and their meaning, implications of results for risk of future cognitive decline, and information about Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s and risk factors. Participants should be screened for anxiety and depression to determine suitability to receive amyloid imaging information. The person conducting the sessions should check comprehension and be skilled in communication and recognizing distress. Imaging should occur on a separate day from consent, and disclosure on a separate day from imaging. Disclosure should occur in person, with time for questions. At disclosure, investigators should assess mood and willingness to receive results, and provide a written results report. Telephone follow-up within a few days should assess the impact of disclosure, and periodic scheduled assessments of depression and anxiety, with additional monitoring and follow-up for participants showing distress, should be performed. We developed a document for use with potential study participants to describe the process of amyloid imaging and the implications of amyloid imaging results; and a disclosure process with attention to ongoing monitoring of both mood and safety to receive this information. This document and process will be used in the A4 Study and can be adapted for other research settings.

Journal of Palliative Medicine, 2002

Improvements in end-of-life care will require an active program of research, and this research wi... more Improvements in end-of-life care will require an active program of research, and this research will need to involve patients in hospice. However, it is not known whether hospices are prepared to participate in research, nor is it known what barriers may prevent hospices from becoming involved in research. This nationwide telephone survey was conducted with a random sample of hospice organizations taken from a national database. Questions elicited the research activities in which hospices are involved, the resources that hospices have available for the ethical review of research, and perceived barriers to research participation. Of 88 hospices identified, 17 (19%) reported that they had participated in research in the past year. Hospices that participated in research were more likely to be urban, affiliated with an academic institution, and were more likely to have an inpatient unit. Hospices cited several barriers to research participation, including time commitments, staffing resources, ethical concerns, and burdens to patients and families. The most important concern was lack of staffing resources. Hospices indicated that they would be most willing to support research regarding pain management and timing of referral to hospice.

Health education & behavior : the official publication of the Society for Public Health Education, 2014

Financial incentives and peer networks could be delivered through eHealth technologies to encoura... more Financial incentives and peer networks could be delivered through eHealth technologies to encourage older adults to walk more. We conducted a 24-week randomized trial in which 92 older adults with a computer and Internet access received a pedometer, daily walking goals, and weekly feedback on goal achievement. Participants were randomized to weekly feedback only (Comparison), entry into a lottery with potential to earn up to $200 each week walking goals were met (Financial Incentive), linkage to four other participants through an online message board (Peer Network), or both interventions (Combined). Main outcomes were the proportion of days walking goals were met during the 16-week intervention and 8-week follow-up. We conducted a content analysis of messages posted by Peer Network and Combined arm participants. During the 16-week intervention, there were no differences in the proportion of days walking goals were met in the Financial Incentive (39.7%; p = .78), Peer Network (24.9%;...

LDI issue brief, 2008

This presidential election year reminds us of the importance of each vote and of the integrity of... more This presidential election year reminds us of the importance of each vote and of the integrity of the electoral process. Recent elections have been decided by very narrow margins. In this context, the voting rights and capacity of persons with dementia warrant attention. About 4.5 million Americans currently live with dementia. Whether these citizens should vote raises a host of ethical, legal, and practical issues. At what point does someone lose the capacity to vote, and who decides? What kinds of assistance should these voters get, and who should provide it? And how can the voting rights of residents in long-term care facilities be protected?

Alzheimers & Dementia, 2011

Memory awareness in early Alzheimer's disease (AD) influences capacity to provide informed consen... more Memory awareness in early Alzheimer's disease (AD) influences capacity to provide informed consent for a memory treatment. This study investigated the extent to which aspects of memory awareness influence everyday decision-making capacity about medication management in AD. 42 participants with mild AD and 50 healthy elders underwent clinical ratings of memory awareness, metamemory testing, and an interview of everyday decision-making capacity regarding medication management. 45% of AD subjects were classified as aware (AAD) and 55% as unaware (UAD) based on clinical ratings and supported by metamemory testing (P = .015). Capacity was impaired in each of the AD groups as compared to the healthy elders F(2, 67) = 17.63, UAD, P < .01; AAD, P = .01). Within the AD group, capacity correlated selectively with awareness as measured with clinical ratings (r = −.41, P = .007) but not objective metamemory testing (r = −.10, P = .60 ). Appreciation scores were lower in UAD as compared with AAD F(1, 35) = 8.36, P = .007. Unawareness of memory loss should heighten clinicians' concern about everyday decision-making capacity in AD.

Neurology, Jan 11, 2015

Prevention trials for neurodegenerative diseases use genetic or other risk marker tests to select... more Prevention trials for neurodegenerative diseases use genetic or other risk marker tests to select participants but there is concern that this could involve coercive disclosure of unwanted information. This has led some trials to use blinded enrollment (participants are tested but not told of their risk marker status). We examined the ethics of blinded vs transparent enrollment using well-established criteria for assessing the ethics of clinical research. Normative analysis applying 4 key ethical criteria-favorable risk-benefit ratio, informed consent, fair subject selection, and scientific validity-to blinded vs transparent enrollment, using current evidence and state of Alzheimer disease (AD) and other prevention trials. Current evidence on the psychosocial impact of risk marker disclosure and considerations of scientific benefit do not support an obligation to use blinded enrollment in prevention trials. Nor does transparent enrollment coerce or involve undue influence of potentia...

Neuropsychology, 2014

Metamemory, or knowledge of one&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s memory ... more Metamemory, or knowledge of one&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s memory abilities, is often impaired in individuals with Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease (AD), although the basis of this metacognitive deficit has not been fully articulated. Behavioral and imaging studies have produced conflicting evidence regarding the extent to which specific cognitive domains (i.e., executive function; memory) and brain regions contribute to memory awareness. The primary aim of this study was to disentangle the cognitive correlates of metamemory in AD by examining the relatedness of objective metamemory performance to cognitive tasks grouped by domain (executive function or memory) as well as by preferential hemispheric reliance defined by task modality (verbal or nonverbal). Eighty-nine participants with mild AD recruited at Columbia University Medical Center and the University of Pennsylvania underwent objective metamemory and cognitive testing. Partial correlations were used to assess the relationship between metamemory and four cognitive variables, adjusted for recruitment site. The significant correlates of metamemory included nonverbal fluency (r = .27, p = .02) and nonverbal memory (r = .24, p = .04). Our findings suggest that objectively measured metamemory in a large sample of individuals with mild AD is selectively related to a set of interdomain nonverbal tasks. The association between metamemory and the nonverbal tasks may implicate a shared reliance on a right-sided cognitive network that spans frontal and temporal regions.

Neurobiology of Aging - NEUROBIOL AGING, 2004

Background: This presentation reports on several trans-cultural/llnguistic studies with the Alzhe... more Background: This presentation reports on several trans-cultural/llnguistic studies with the Alzheimer's Quick Test (AQT). AQT Color-Form Naming (AQT-CF) is currently used as part of a neurnpsychological testing in a longitudinal study of adults with normal cognitive functioning and with mild-to-moderate AD (University Hospital MAS, Sweden). It has been accepted for inclusion in the EU Consortium Centre studies of Alzheimer's Disease (DESCRIPA). Objective(s): The purpose was to establish if AQT naming times (sec.) would differentiate between adults from different language and cultural backgrounds with and without cognitive impairments and to compare discriminant values of AQT with MMSE scores. Methods:

New England Journal of Medicine, 2012

Nature Genetics, 2011

A sonnen 95 , salvatore spina 63 , Robert A stern 31 , Rudolph e tanzi 67 , John Q trojanowski 6 ... more A sonnen 95 , salvatore spina 63 , Robert A stern 31 , Rudolph e tanzi 67 , John Q trojanowski 6 , Juan c troncoso 96 , Vivianna m Van deerlin 6 , Harry V Vinters 49,97 , Jean Paul Vonsattel 98 , sandra weintraub 85,86 , kathleen A welsh-Bohmer 41,99 , Jennifer williamson 70 , Randall l woltjer 100 , laura B cantwell 6 , Beth A dombroski 6 , duane Beekly 101 , kathryn l lunetta 2 , eden R martin 1,5 , m Ilyas kamboh 30,79 , Andrew J saykin 54,102 , eric m Reiman 28,103-105 , david A Bennett 22,106 , John c morris 42,107 , thomas J montine 95 , Alison m goate 23 , deborah Blacker 108,109 , debby w tsuang 91 , Hakon Hakonarson 110 , walter A kukull 111 , tatiana m Foroud 54 , Jonathan l Haines 112,113 , Richard mayeux 70,114 , margaret A Pericak-Vance 1,5 , lindsay A Farrer 2-4,31,32 & gerard d schellenberg 6

International Journal of Geriatric Psychiatry, 2007

Objective Depression occurs frequently in patients with both Alzheimer's disease (AD) and Parkins... more Objective Depression occurs frequently in patients with both Alzheimer's disease (AD) and Parkinson's disease (PD), but there has been little comparison of depression symptoms in the two populations. Method The 15-item Geriatric Depression Scale (GDS-15) was administered as a depression screening instrument to 232 AD patients and 266 PD specialty care patients with at most mild dementia. Logistic regression models were used to determine disease-specific associations with individual GDS-15 items, and factor analysis was used to assess GDS-15 factor structure in the two populations. Results Controlling for total GDS-15 score and other covariates, AD patients reported more dissatisfaction with life ( p ¼ 0.03) and memory problems ( p < 0.001), while PD patients reported more fearfulness ( p ¼ 0.01), helplessness ( p < 0.01), a preference to stay at home ( p ¼ 0.02), and diminished energy ( p < 0.01). Three factors were generated in PD (explaining 55% of the total variance) and five in AD (explaining 59% of the total variance), and the two main factors generated in both populations related primarily to unhappiness and negative thoughts. Conclusions The factor structure of the GDS-15 is similar in AD and PD patients with at most mild stage dementia, but between-group differences on 6 of the GDS-15 items suggests the non-specificity of certain items in the two populations.

Alzheimer's & Dementia, 2006

Balancing benefits and risks in the development of treatments for Alzheimer's disease is challeng... more Balancing benefits and risks in the development of treatments for Alzheimer's disease is challenging given the nature of the disease but critically important to ensure effective treatments are available. Drawing on a diverse panel of scientists, regulators, caregivers, patients and advocates convened by the Alzheimer's Association, insights are offered into benefit/risk assessment, decision-making, regulatory and societal factors affecting clinical trials on AD. Several policy solutions are offered to improve the drug testing, review and approval process.

Alzheimer's & Dementia, 2006

Acta Neuropathologica, 2010

Altered levels of cerebrospinal fluid (CSF) peptides related to Alzheimer's disease (AD) are asso... more Altered levels of cerebrospinal fluid (CSF) peptides related to Alzheimer's disease (AD) are associated with pathologic AD diagnosis, although cognitively normal subjects can also have abnormal levels of these AD biomarkers. To identify novel CSF biomarkers that distinguish pathologically confirmed AD from cognitively normal subjects and patients with other neurodegenerative disorders, we collected antemortem CSF samples from 66 AD patients and 25 patients with other neurodegenerative dementias followed longitudinally to neuropathologic confirmation, plus CSF from 33 cognitively normal subjects. We measured levels of 151 novel analytes via a targeted multiplex panel enriched in cytokines, chemokines and growth factors, as well as established AD CSF biomarkers (levels of Aβ42, tau and p-tau 181 ). Two categories of biomarkers were identified: (1) analytes that specifically distinguished AD (especially CSF Aβ42 levels) from cognitively normal subjects and other disorders; and (2) analytes altered in multiple diseases (NrCAM, PDGF, C3, IL-1α), but not in cognitively normal subjects. A multiprong analytical approach showed AD patients were best distinguished from non-AD cases (including cognitively normal subjects and patients with other neurodegenerative disorders) by a combination of traditional AD biomarkers and novel multiplex biomarkers. Six novel biomarkers (C3, CgA, IL-1α, I-309, NrCAM and VEGF) were correlated with the severity of cognitive impairment at CSF collection, and altered levels of IL-1α and TECK associated with subsequent cognitive decline in 38 longitudinally followed subjects with mild cognitive impairment. In summary, our targeted proteomic screen revealed novel CSF biomarkers that can improve the distinction between AD and non-AD cases by established biomarkers alone.

Journal of pain and symptom management, 2003

This paper examines the conditions that describe when it is appropriate to conduct research that ... more This paper examines the conditions that describe when it is appropriate to conduct research that enrolls a subject near the end-of-life who cannot provide an informed consent. Specifically, it describes conditions that justify when it is acceptable to expose a person to the risks, burdens or discomforts of an intervention that is not intended to benefit that person but to produce generalizable knowledge that will benefit other people. These conditions are: (1) acceptable research risks, (2) proxy decision making, (3) subject assent and dissent, and (4) subject advance consent.

The New England journal of medicine, Jan 3, 2003

... 33. Freedman B . Scientific value and validity as ethical requirements for research: a propos... more ... 33. Freedman B . Scientific value and validity as ethical requirements for research: a proposed explication. IRB 1987;9:7-10 CrossRef | Medline. 34. ... 36. National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research . ...

LDI issue brief, 2002

About four million Americans currently live with Alzheimer's disease (AD) or related forms of... more About four million Americans currently live with Alzheimer's disease (AD) or related forms of dementia. Because the disease process impairs language, insight, and judgment, family members become "caregivers." These caregivers, either in part or in full, often make decisions on patients' behalf. This Issue Brief summarizes a series of studies that describe how caregivers make decisions for AD patients, and caregiver perspectives on the quality of life for relatives with AD.

To explore the factors that patients with malignant and nonmalignant pain consider when deciding ... more To explore the factors that patients with malignant and nonmalignant pain consider when deciding whether to enroll in pain research studies, determine whether their views are different, and determine whether willingness to enroll in research is associated with pain severity, semistructured interviews were conducted with 80 patients (cancer pain: n ϭ 40; chronic nonmalignant pain: n ϭ 40). The risks and potential benefits that were important to patients with cancer were the same as those that were important to patients with chronic pain. Willingness to enroll in research was associated with pain severity (Spearman ϭ 0.33; P ϭ 0.041) in patients with chronic pain, but not in patients with cancer pain. Patients with cancer pain do not have different concerns than chronic pain patients do. Although chronic pain patients' willingness to enroll in research was related to pain severity and a desire for better pain management, cancer patients' willingness to enroll was not.

Objective-To determine whether participants with mild cognitive impairment (MCI) differ from cogn... more Objective-To determine whether participants with mild cognitive impairment (MCI) differ from cognitively normal (NC) older adults on traditional and novel informant-based measures of activities of daily living (ADL) and to identify cognitive correlates of ADLs among participants with MCI.

Alzheimer's & Dementia, 2014

The objective of this study was to develop a process to maximize the safety and effectiveness of ... more The objective of this study was to develop a process to maximize the safety and effectiveness of disclosing Positron Emission Tomography (PET) amyloid imaging results to cognitively normal older adults participating in Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease secondary prevention studies such as the Anti-Amyloid Treatment in Asymptomatic Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s Disease (A4) Study. Using a modified Delphi Method to develop consensus on best practices, we gathered and analyzed data over three rounds from experts in two relevant fields: informed consent for genetic testing or human amyloid imaging. Experts reached consensus on (1) text for a brochure that describes amyloid imaging to a person who is considering whether to undergo such imaging in the context of a clinical trial, and (2) a process for amyloid PET result disclosure within such trials. Recommendations included: During consent, potential participants should complete an educational session, where they receive verbal and written information covering what is known and unknown about amyloid imaging, including possible results and their meaning, implications of results for risk of future cognitive decline, and information about Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s and risk factors. Participants should be screened for anxiety and depression to determine suitability to receive amyloid imaging information. The person conducting the sessions should check comprehension and be skilled in communication and recognizing distress. Imaging should occur on a separate day from consent, and disclosure on a separate day from imaging. Disclosure should occur in person, with time for questions. At disclosure, investigators should assess mood and willingness to receive results, and provide a written results report. Telephone follow-up within a few days should assess the impact of disclosure, and periodic scheduled assessments of depression and anxiety, with additional monitoring and follow-up for participants showing distress, should be performed. We developed a document for use with potential study participants to describe the process of amyloid imaging and the implications of amyloid imaging results; and a disclosure process with attention to ongoing monitoring of both mood and safety to receive this information. This document and process will be used in the A4 Study and can be adapted for other research settings.

The general public’s views can influence whether people with Alzheimer’s disease (AD) experience ... more The general public’s views can influence whether people with Alzheimer’s disease (AD) experience stigma. The purpose of this study was to understand what characteristics in the general public are associated with stigmatizing attributions. A random sample of adults from the general population read a vignette about a man with mild Alzheimer’s disease dementia and completed a modified Family Stigma in Alzheimer’s Disease Scale (FS-ADS). Multivariable ordered logistic regressions were used to examine relationships between personal characteristics and FS-ADS ratings. Older respondents expected that persons with AD would receive less support (OR=0.82, p=.001), have social interactions limited by others (OR=1.13, p=.04), and face institutional discrimination (OR=1.13, p=.04). Females reported stronger feelings of pity (OR=1.57, p=.03) and weaker reactions to negative aesthetic features (OR=0.67, p=.05). Those who believed strongly that AD was a mental illness rated symptoms more severely (OR=1.78, p=.007). Identifiable characteristics and beliefs in the general public are related to stigmatizing attributions toward AD. To reduce AD stigma, public health messaging campaigns can tailor information to subpopulations, recognizable by their age, gender, and beliefs.