- Email: [email protected]
Tau sites abnormally phosphorylated and protein kinases and phosphatases involved
Featured Research Session F3-02: Twenty-Five Years of Abnormal Hyperphosphorylation of Tau while relinquished caregivers demonstrate a decline after relinquishment. This reflects the influence of grief, which declines with time for bereaved caregivers, but increases as continuing caregivers and relinquished caregivers maintain their current statuses. There is also some support for the predictive role of grief in understanding wellbeing, with evidence that psychological outcomes in particular are strongly linked to an individual’s grief experience. Conclusions: From a multivariate perspective however, there are few significant differences between the wellbeing of relinquished and bereaved caregivers. The data presented will demonstrate the benefits of longitudinal research in providing an understanding of the caregiving journey, including the consequences which emerge following relinquishment of care. F3-01-05
RISK FACTORS ASSOCIATED WITH NURSING HOME PLACEMENT IN COGNITIVE IMPAIRMENT NOT DEMENTIA (CIND) AND DEMENTIA PATIENTS: DATA FROM THE ACCORD STUDY
Ging-Yuek Robin Hsiung1, Kateryna Vostretsova1, Claudia Jacova1, Jon Money1, Howard Feldman1,2, ACCORD INVESTIGATORS,1University of British Columbia, Vancouver, BC, Canada; 2Bristol-Myers Squibb, Wallingford, CT, USA. Contact e-mail: [email protected] Background: Dementia carries a heavy societal burden in cost of care, with long-term institutionalization being a major cost driver. Understanding early predictors of institutional care could optimize resource utilization and programmatic development. We examined factors associated with early institutionalization using data from the ACCORD study. Methods: Subjects were enrolled in a longitudinal cohort (n¼1136) across 8 specialized dementia clinics in Canada. Subjects’ living locations were ascertained at 1- and 2-year follow up. We compared demographic and clinical characteristics of subjects who required nursing home placement at 2 years of follow up compared to those who remained at home. Demographic variables including age, sex, education, marital status, and clinical variables including dementia subtype, Mini Mental Status Exam (MMSE), Disability Assessment for Dementia (DAD), Functional Rating Scale (FRS), Neuropsychiatric Inventory (NPI), and Cumulative Illness Rating Scale (CIRS) were examined. Categorical variables were initially screened with chi-square statistic, and continuous variables were compared using t-tests. Further modeling with logistic regression was used to obtain odds ratios and to adjust for multiple variables. Results: The proportion of subjects placed in nursing home after 2 years was 1.8% for not cognitively impaired, 6.1% for CIND, and 12.4% for dementia. Within the dementia subtypes, Lewy Body Dementia (LBD) had the highest proportion (37%) placed in nursing homes after 2 years compared to other dementias (4-12%). Females (p<0.001), no spouse (p<0.001), and older age (p<0.001) were all factors strongly associated with nursing home placement. Baseline measures of cognitive and functional status including MMSE, DAD, FRS, and NPI were also significant predictors (p<0.001) of nursing home placement. However, CIRS was not (p¼0.38). After logistic regression modeling examining all significant variables, only marital status (p<0.001) and DAD (p<0.001) scores remain significant. Conclusions: Among the different types of dementia, LBD has the highest risk of early nursing home placement. While age, sex, marital status, MMSE, DAD, FRS, and NPI are all associated with increased risk of nursing home placements, a number of these factors are highly correlated. Preservation of activities of daily living (ADL) skills, as measured by DAD, appears to be the most important target to achieve a delay in nursing home placement. F3-01-06
HOSPICE CARE IN U.S. NURSING HOMES FOR PERSONS WITH END-STAGE DEMENTIA: HOW U.S. MEDICARE PAYMENT POLICY INFLUENCES HOSPICE ELECTION AND END-OF-LIFE HOSPITALIZATIONS
Susan C. Miller1, Julie C. Lima1, Susan L. Mitchell2, 1Brown University, Providence, RI, USA; 2Hebrew SeniorLife Institute for Aging Research, Boston, MA, U.S. Contact e-mail: [email protected]
S117
Background: Over 60 percent of older Americans who die with dementia each year die in nursing homes (NHs). While studies show benefits associated with NH Medicare hospice enrollment, U.S. government regulations prohibit NH residents from simultaneously accessing Medicare hospice care and Medicare financed NH care (i.e., skilled nursing facility [SNF] care), and it is financially disadvantageous for residents/families and for NHs to switch from Medicare NH care to hospice care. Methods: For years 1999 through 2006 in the 50 U.S. states and the District of Columbia we merged resident assessment data (MDS) with Medicare data to identify NH decedents with end-stage dementia (i.e., an MDS dementia diagnosis and severe to very severe dementia per the cognitive performance scale). We identified for years 1999-2006 the proportion of decedents who received Medicare hospice and their hospice lengths of stay. In 2006, we identified residents receiving Medicare-reimbursed SNF care in the last 90 days of life, and for these, we determined the proportion electing hospice, hospice lengths of stay, and the prevalence of end-of-life hospitalizations (by hospice enrollment). Results: A significantly higher proportion of NH decedents with end-stage dementia enrolled in NH hospice in 2006 compared to 1999 (40% versus 13% respectively). Also, mean hospice stays were longer in 2006 versus in 1999 (149 versus 49 days respectively), as were median stays (39 days versus 16 respectively). In 2006, hospice enrollment differed for residents who did and did not receive Medicare SNF care in the last 90 days of life; 32% with versus 43% without SNF care enrolled in hospice. Those SNF residents who did enroll in hospice, compared to SNF residents who did not enroll in hospice, had significantly fewer hospitalizations in the last 90 days of life and were significantly less likely to die in a hospital (1% versus 17% respectively; p<.001). Conclusions: There has been much growth in the use and earlier use of Medicare hospice by NH residents with end-stage dementia. However, government policy appears to be associated with lower hospice enrollment by SNF residents and in resulting greater hospital use. TUESDAY, JULY 13, 2010 FEATURED RESEARCH SESSION F3-02 TWENTY-FIVE YEARS OF ABNORMAL HYPERPHOSPHORYLATION OF TAU F3-02-01
TAU SITES ABNORMALLY PHOSPHORYLATED AND PROTEIN KINASES AND PHOSPHATASES INVOLVED
Simon Lovestone, Richard Killick, King’s College London, London, United Kingdom. Contact e-mail: [email protected] Wnt and Insulin signalling regulation of the amyloid cascade Simon Lovestone, Richard Killick, Elena Ribe-Garrido, Alvina To et al One of the key tau kinases, GSK3, is regulated by two canonical pathways e insulin and wnt. Evidence, ranging from epidemiology through genetics to in vitro studies, has been provided that either or both pathways are altered in Alzheimer’s disease suggesting that either might provide a novel therapeutic target. It becomes important therefore to discover whether both pathways are equal in their effects on AD pathogenesis and to define in more detail the pathways that might lead from Abeta pathology to tau pathology and hence neuronal death. In order to do this we have generated three animal models. In the first we crossed insulin resistant mice lacking Irs2 with Tg2576 Ab generating animals and in the second we have over-expressed Dkk1, an inhibitor of wnt signalling. In both sets of animals we identify various pathological markers including alteration in fibrillised Ab deposits, altered tau phosphorylation and altered gene expression patterns that we have also shown to be altered in AD brain. In a third set of experiments we have utilised mice humanised for APOE fed with both normal and high fat diets to induce insulin resistance. These too have altered tau phosphorylation at a series of epitopes. These data show that whilst both pathways can influence AD pathogenesis, both also have complex effects when altered in vivo. Based upon these animal models we will show data suggesting that the wnt signalling pathways yields specific and plausible therapeutic targets but that insulin signalling alters both amyloid and tau pathologies in opposite directions and that therefore therapeutic intervention in this pathway may be problematical in the context of AD.
RISK FACTORS ASSOCIATED WITH NURSING HOME PLACEMENT IN COGNITIVE IMPAIRMENT NOT DEMENTIA (CIND) AND DEMENTIA PATIENTS: DATA FROM THE ACCORD STUDY
Ging-Yuek Robin Hsiung1, Kateryna Vostretsova1, Claudia Jacova1, Jon Money1, Howard Feldman1,2, ACCORD INVESTIGATORS,1University of British Columbia, Vancouver, BC, Canada; 2Bristol-Myers Squibb, Wallingford, CT, USA. Contact e-mail: [email protected] Background: Dementia carries a heavy societal burden in cost of care, with long-term institutionalization being a major cost driver. Understanding early predictors of institutional care could optimize resource utilization and programmatic development. We examined factors associated with early institutionalization using data from the ACCORD study. Methods: Subjects were enrolled in a longitudinal cohort (n¼1136) across 8 specialized dementia clinics in Canada. Subjects’ living locations were ascertained at 1- and 2-year follow up. We compared demographic and clinical characteristics of subjects who required nursing home placement at 2 years of follow up compared to those who remained at home. Demographic variables including age, sex, education, marital status, and clinical variables including dementia subtype, Mini Mental Status Exam (MMSE), Disability Assessment for Dementia (DAD), Functional Rating Scale (FRS), Neuropsychiatric Inventory (NPI), and Cumulative Illness Rating Scale (CIRS) were examined. Categorical variables were initially screened with chi-square statistic, and continuous variables were compared using t-tests. Further modeling with logistic regression was used to obtain odds ratios and to adjust for multiple variables. Results: The proportion of subjects placed in nursing home after 2 years was 1.8% for not cognitively impaired, 6.1% for CIND, and 12.4% for dementia. Within the dementia subtypes, Lewy Body Dementia (LBD) had the highest proportion (37%) placed in nursing homes after 2 years compared to other dementias (4-12%). Females (p<0.001), no spouse (p<0.001), and older age (p<0.001) were all factors strongly associated with nursing home placement. Baseline measures of cognitive and functional status including MMSE, DAD, FRS, and NPI were also significant predictors (p<0.001) of nursing home placement. However, CIRS was not (p¼0.38). After logistic regression modeling examining all significant variables, only marital status (p<0.001) and DAD (p<0.001) scores remain significant. Conclusions: Among the different types of dementia, LBD has the highest risk of early nursing home placement. While age, sex, marital status, MMSE, DAD, FRS, and NPI are all associated with increased risk of nursing home placements, a number of these factors are highly correlated. Preservation of activities of daily living (ADL) skills, as measured by DAD, appears to be the most important target to achieve a delay in nursing home placement. F3-01-06
HOSPICE CARE IN U.S. NURSING HOMES FOR PERSONS WITH END-STAGE DEMENTIA: HOW U.S. MEDICARE PAYMENT POLICY INFLUENCES HOSPICE ELECTION AND END-OF-LIFE HOSPITALIZATIONS
Susan C. Miller1, Julie C. Lima1, Susan L. Mitchell2, 1Brown University, Providence, RI, USA; 2Hebrew SeniorLife Institute for Aging Research, Boston, MA, U.S. Contact e-mail: [email protected]
S117
Background: Over 60 percent of older Americans who die with dementia each year die in nursing homes (NHs). While studies show benefits associated with NH Medicare hospice enrollment, U.S. government regulations prohibit NH residents from simultaneously accessing Medicare hospice care and Medicare financed NH care (i.e., skilled nursing facility [SNF] care), and it is financially disadvantageous for residents/families and for NHs to switch from Medicare NH care to hospice care. Methods: For years 1999 through 2006 in the 50 U.S. states and the District of Columbia we merged resident assessment data (MDS) with Medicare data to identify NH decedents with end-stage dementia (i.e., an MDS dementia diagnosis and severe to very severe dementia per the cognitive performance scale). We identified for years 1999-2006 the proportion of decedents who received Medicare hospice and their hospice lengths of stay. In 2006, we identified residents receiving Medicare-reimbursed SNF care in the last 90 days of life, and for these, we determined the proportion electing hospice, hospice lengths of stay, and the prevalence of end-of-life hospitalizations (by hospice enrollment). Results: A significantly higher proportion of NH decedents with end-stage dementia enrolled in NH hospice in 2006 compared to 1999 (40% versus 13% respectively). Also, mean hospice stays were longer in 2006 versus in 1999 (149 versus 49 days respectively), as were median stays (39 days versus 16 respectively). In 2006, hospice enrollment differed for residents who did and did not receive Medicare SNF care in the last 90 days of life; 32% with versus 43% without SNF care enrolled in hospice. Those SNF residents who did enroll in hospice, compared to SNF residents who did not enroll in hospice, had significantly fewer hospitalizations in the last 90 days of life and were significantly less likely to die in a hospital (1% versus 17% respectively; p<.001). Conclusions: There has been much growth in the use and earlier use of Medicare hospice by NH residents with end-stage dementia. However, government policy appears to be associated with lower hospice enrollment by SNF residents and in resulting greater hospital use. TUESDAY, JULY 13, 2010 FEATURED RESEARCH SESSION F3-02 TWENTY-FIVE YEARS OF ABNORMAL HYPERPHOSPHORYLATION OF TAU F3-02-01
TAU SITES ABNORMALLY PHOSPHORYLATED AND PROTEIN KINASES AND PHOSPHATASES INVOLVED
Simon Lovestone, Richard Killick, King’s College London, London, United Kingdom. Contact e-mail: [email protected] Wnt and Insulin signalling regulation of the amyloid cascade Simon Lovestone, Richard Killick, Elena Ribe-Garrido, Alvina To et al One of the key tau kinases, GSK3, is regulated by two canonical pathways e insulin and wnt. Evidence, ranging from epidemiology through genetics to in vitro studies, has been provided that either or both pathways are altered in Alzheimer’s disease suggesting that either might provide a novel therapeutic target. It becomes important therefore to discover whether both pathways are equal in their effects on AD pathogenesis and to define in more detail the pathways that might lead from Abeta pathology to tau pathology and hence neuronal death. In order to do this we have generated three animal models. In the first we crossed insulin resistant mice lacking Irs2 with Tg2576 Ab generating animals and in the second we have over-expressed Dkk1, an inhibitor of wnt signalling. In both sets of animals we identify various pathological markers including alteration in fibrillised Ab deposits, altered tau phosphorylation and altered gene expression patterns that we have also shown to be altered in AD brain. In a third set of experiments we have utilised mice humanised for APOE fed with both normal and high fat diets to induce insulin resistance. These too have altered tau phosphorylation at a series of epitopes. These data show that whilst both pathways can influence AD pathogenesis, both also have complex effects when altered in vivo. Based upon these animal models we will show data suggesting that the wnt signalling pathways yields specific and plausible therapeutic targets but that insulin signalling alters both amyloid and tau pathologies in opposite directions and that therefore therapeutic intervention in this pathway may be problematical in the context of AD.