- Email: [email protected]
Proteolytic processing of membrane anchored Neuregulin1 in cell culture
P228 P1-173
Poster Presentations P1 PROTEOLYTIC PROCESSING OF MEMBRANE ANCHORED NEUREGULIN1 IN CELL CULTURE
Shin-ichi Tatsumi, Masayasu Okochi, Shinji Tagami, Takashi Kodama, Kanta Yanagida, Taisuke Nakayama, Kohji Mori, Takashi Morihara, Hitoshi Tanimukai, Ryota Hashimoto, Toshihisa Tanaka, Takashi Kudo, Masatoshi Takeda, Osaka University Graduate School of Medicine, Suita, Osaka, Japan. Contact e-mail: [email protected] Background: BACE1/2 play an essential role for Neuregulin1 (NRG1)-related peripheral myelination. Here, we studied sequential proteolytic processing of NRG1. Methods: NRG1b1/1b2 were stably expressed and analyzed their degradation in cultured cell. Soluble ectodomain NRG1, generated by proteolysis at the juxtamembrane region of the full-length form, and secreted Abeta-like peptides were searched. Results: We revealed that Abeta-like peptides derived from NRG1b1 but not NRG1b2 were produced mainly by a combination of the alpha- and gamma-secretases. The mechanism is reminiscent of production of Nbeta/p3 peptides. We still have not reached any conclusion whether BACE1/2 play roles in the production of soluble ectodomain NRG1b1/1b2. Conclusions: Further studies are necessary how BACE1/2 involve in NRG1-related peripheral myelination. P1-174
CAREGIVER DIFFERENCES IN RESPONSE TO A PSYCHOBEHAVIORAL INTERVENTION FOR CAREGIVERS OF ALZHEIMER’S DISEASE PATIENTS: HIGHLIGHTS FROM REACH II
Sara J. Czaja1, Chin Chin Lee2, Richard Schulz3, 1University of Miami Miller School of Medicine/Department of Psychiatry and Behavioral Sciences, Miami, FL, USA; 2University of Miami Miller School of Medicine/ Center on Aging, Miami, FL, USA; 3University of Pittsburgh/Department of Psychiatry, Pittsburgh, PA, USA. Contact e-mail: [email protected] Background: Most people who have Alzheimer’s disease (AD) are cared for by family members. Many caregivers experience negative emotional and physical health consequences in response to caregiving. Therefore, it is important to identify strategies to alleviate caregiver distress and to understand how caregiver characteristics influence the caregiving experience and responses to intervention programs. Methods: This presentation presents data on from the Resources for Enhancing Alzheimer’s Caregiver’s Health (REACH II) program, a multi-component psychosocial intervention aimed at reducing the risk for adverse outcomes among informal caregivers of patients with dementia. The sample included 211 Black/AA, 212 Hispanic American and 219 White Non-Hispanics caregiver/patient dyads who were randomly assigned to the treatment or control condition following a baseline assessment. We discuss differences among the caregivers in important indices of caregiver quality of life including social support, self-care activities and patient problem behaviors. We use a stepwise hierarchical regression approach to examine how response to the intervention was moderated by caregiver characteristics (e.g., age, education, relationship to the patient). Results: The results indicated that there were ethnic/cultural differences in perceptions of social support, self-care activities and patient problem behaviors at baseline. For example, Hispanic caregivers reported higher patient problem behaviors and perceived social support. The effects of the intervention within the ethnic groups were moderated by different caregiver characteristics. For example, among Hispanic caregivers, older caregivers who received the intervention reported fewer patient problem behaviors at follow-up (B¼-.07, p<.05) and among Black/African Americans caregivers with more years of caregiving who received the intervention reported fewer problem behaviors (B¼-.24, p <.05). With respect to self-care behaviors, among the Hispanic caregivers those who had more years of caregiving (B¼.06, p<.05), more education (B¼.10, p<.05) and who received the intervention (B¼-.80, p,.05) reported better self-care at follow-up whereas among the Black/African Americans those who were spouses and received the intervention (B¼-.20,p<.05) reported improvements in self-care. Conclusions: The results indicate that response to caregiving and caregiver interventions varies as function of needs and characteristics of caregivers. It is important to tailor intervention programs to the needs of caregivers to maximize the benefits of these programs.
P1-175
LOST IN THE MIST: ALZHEIMER’S AND ABUSE
Robin T. Hatcher, Hale County DHR, Greensboro, AL, USA. Contact e-mail: [email protected] Background: Persons suffering from Alzheimer’s Disease and their care providers may feel as though they are lost in a mist that never clears. Investigating cases of elder abuse within the Alzheimer’s population is a trend that is on the rise. Methods: The investigator must utilize all of the 5 senses of taste, touch, smell, sight and sound in order to obtain an accurate picture of what is going on within the Alzheimer’s patients world. The patients physical and mental status must be thoroughly assessed along with their environment and the care, or the lack of it, they receive from their care providers. Caregiving issues are at the core of reports of elder abuse, neglect and/or exploitation. Results: Once a case of elder abuse has been detected, a plan of protection must be formulated to protect the victim whereby family members and community resources are called upon to assist. The plan of protection includes all areas of the patient’s world such as their physical, mental, environmental and monetary status as well as that of their care providers. Education and support should be offered to the patients and their care providers in order to provide them with information regarding the issues associated with Alzheimer’s Disease, relief of stress, and choices, so the patients will be safe within their environment. Conclusions: Education, support and protection are the keys to helping Alzheimer’s patients and their care providers navigate safely through the mist of Alzheimer’s Disease. P1-176
CLINICAL CORRELATES OF CAREGIVER BURDEN IN ALZHEIMER’S DISEASE
Somaia Mohamed1, Robert Rosenheck1, Lon Schneider2, 1Yale School of Medicine, West Haven, CT, USA; 2University of Southern California Keck School of Medicine, Los Angeles, CA, USA. Contact e-mail: somaia. [email protected] Background: Alzheimer disease (AD) imposes a severe burden upon patients and their caregivers. Caregivers often experience significant psychological, physical, and social stresses. Although there is substantial evidence of the adverse impact of burden, considerably less is known about its specific correlates and potential causes. Methods: We use data from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE)-AD study to examine the relationship of three measures of burden among AD caregivers to both patient and caregiver sociodemographic characteristics, measures of patients’ cognitive status, psychiatric and behavioral symptoms, functional abilities, quality of life, and to the intensity of care provided by caregivers. Results: More severe psychiatric and behavioral problems and decreased patient quality of life, as well as lower functional abilities were significantly associated with higher levels of burden and depression among caregivers at baseline. Correaltion of six six-month changes showed that relative symptom reductions and improvements in quality of life were associated with decreased burden and accounted for most of the explained variance in change of burden. Conclusions: Severity of psychiatric symptoms and behavioral disturbances and patients’ quality of life are the main determinants of caregivers’ perception of burden. Effective interventions targeting these two aspects of the disorder are likely to not only alleviate patient suffering but also promote caregiver well-being. P1-177
NEUROPSYCHIATRIC INVENTORY FOR ALZHEIMER’S DISEASE AND MILD COGNITIVE IMPAIRMENT’S PATIENTS WITH NEW CLASSIFICATION METHODS
Taewan Kim, Jinsuk Kim, Jangjun Lee, Jongwhan Choi, Sangwon Park, Yongkook Cho, Daegu Fatima Hospital, Daegu, Republic of Korea. Contact e-mail: [email protected] Background: Diverse neuropsychiatric symptoms (NPS) may manifest according to AD severity. We try to determine what kinds of symptoms are frequent according to subdivided AD groups than usual. We also would like to verify which symptoms are more correlate with ADL. Methods: We prospective and consecutive recruits 73 AD and MCI patients. MCI was defined with DSM -IV criteria. Probable AD was diagnosed according to NINDS-
Poster Presentations P1 PROTEOLYTIC PROCESSING OF MEMBRANE ANCHORED NEUREGULIN1 IN CELL CULTURE
Shin-ichi Tatsumi, Masayasu Okochi, Shinji Tagami, Takashi Kodama, Kanta Yanagida, Taisuke Nakayama, Kohji Mori, Takashi Morihara, Hitoshi Tanimukai, Ryota Hashimoto, Toshihisa Tanaka, Takashi Kudo, Masatoshi Takeda, Osaka University Graduate School of Medicine, Suita, Osaka, Japan. Contact e-mail: [email protected] Background: BACE1/2 play an essential role for Neuregulin1 (NRG1)-related peripheral myelination. Here, we studied sequential proteolytic processing of NRG1. Methods: NRG1b1/1b2 were stably expressed and analyzed their degradation in cultured cell. Soluble ectodomain NRG1, generated by proteolysis at the juxtamembrane region of the full-length form, and secreted Abeta-like peptides were searched. Results: We revealed that Abeta-like peptides derived from NRG1b1 but not NRG1b2 were produced mainly by a combination of the alpha- and gamma-secretases. The mechanism is reminiscent of production of Nbeta/p3 peptides. We still have not reached any conclusion whether BACE1/2 play roles in the production of soluble ectodomain NRG1b1/1b2. Conclusions: Further studies are necessary how BACE1/2 involve in NRG1-related peripheral myelination. P1-174
CAREGIVER DIFFERENCES IN RESPONSE TO A PSYCHOBEHAVIORAL INTERVENTION FOR CAREGIVERS OF ALZHEIMER’S DISEASE PATIENTS: HIGHLIGHTS FROM REACH II
Sara J. Czaja1, Chin Chin Lee2, Richard Schulz3, 1University of Miami Miller School of Medicine/Department of Psychiatry and Behavioral Sciences, Miami, FL, USA; 2University of Miami Miller School of Medicine/ Center on Aging, Miami, FL, USA; 3University of Pittsburgh/Department of Psychiatry, Pittsburgh, PA, USA. Contact e-mail: [email protected] Background: Most people who have Alzheimer’s disease (AD) are cared for by family members. Many caregivers experience negative emotional and physical health consequences in response to caregiving. Therefore, it is important to identify strategies to alleviate caregiver distress and to understand how caregiver characteristics influence the caregiving experience and responses to intervention programs. Methods: This presentation presents data on from the Resources for Enhancing Alzheimer’s Caregiver’s Health (REACH II) program, a multi-component psychosocial intervention aimed at reducing the risk for adverse outcomes among informal caregivers of patients with dementia. The sample included 211 Black/AA, 212 Hispanic American and 219 White Non-Hispanics caregiver/patient dyads who were randomly assigned to the treatment or control condition following a baseline assessment. We discuss differences among the caregivers in important indices of caregiver quality of life including social support, self-care activities and patient problem behaviors. We use a stepwise hierarchical regression approach to examine how response to the intervention was moderated by caregiver characteristics (e.g., age, education, relationship to the patient). Results: The results indicated that there were ethnic/cultural differences in perceptions of social support, self-care activities and patient problem behaviors at baseline. For example, Hispanic caregivers reported higher patient problem behaviors and perceived social support. The effects of the intervention within the ethnic groups were moderated by different caregiver characteristics. For example, among Hispanic caregivers, older caregivers who received the intervention reported fewer patient problem behaviors at follow-up (B¼-.07, p<.05) and among Black/African Americans caregivers with more years of caregiving who received the intervention reported fewer problem behaviors (B¼-.24, p <.05). With respect to self-care behaviors, among the Hispanic caregivers those who had more years of caregiving (B¼.06, p<.05), more education (B¼.10, p<.05) and who received the intervention (B¼-.80, p,.05) reported better self-care at follow-up whereas among the Black/African Americans those who were spouses and received the intervention (B¼-.20,p<.05) reported improvements in self-care. Conclusions: The results indicate that response to caregiving and caregiver interventions varies as function of needs and characteristics of caregivers. It is important to tailor intervention programs to the needs of caregivers to maximize the benefits of these programs.
P1-175
LOST IN THE MIST: ALZHEIMER’S AND ABUSE
Robin T. Hatcher, Hale County DHR, Greensboro, AL, USA. Contact e-mail: [email protected] Background: Persons suffering from Alzheimer’s Disease and their care providers may feel as though they are lost in a mist that never clears. Investigating cases of elder abuse within the Alzheimer’s population is a trend that is on the rise. Methods: The investigator must utilize all of the 5 senses of taste, touch, smell, sight and sound in order to obtain an accurate picture of what is going on within the Alzheimer’s patients world. The patients physical and mental status must be thoroughly assessed along with their environment and the care, or the lack of it, they receive from their care providers. Caregiving issues are at the core of reports of elder abuse, neglect and/or exploitation. Results: Once a case of elder abuse has been detected, a plan of protection must be formulated to protect the victim whereby family members and community resources are called upon to assist. The plan of protection includes all areas of the patient’s world such as their physical, mental, environmental and monetary status as well as that of their care providers. Education and support should be offered to the patients and their care providers in order to provide them with information regarding the issues associated with Alzheimer’s Disease, relief of stress, and choices, so the patients will be safe within their environment. Conclusions: Education, support and protection are the keys to helping Alzheimer’s patients and their care providers navigate safely through the mist of Alzheimer’s Disease. P1-176
CLINICAL CORRELATES OF CAREGIVER BURDEN IN ALZHEIMER’S DISEASE
Somaia Mohamed1, Robert Rosenheck1, Lon Schneider2, 1Yale School of Medicine, West Haven, CT, USA; 2University of Southern California Keck School of Medicine, Los Angeles, CA, USA. Contact e-mail: somaia. [email protected] Background: Alzheimer disease (AD) imposes a severe burden upon patients and their caregivers. Caregivers often experience significant psychological, physical, and social stresses. Although there is substantial evidence of the adverse impact of burden, considerably less is known about its specific correlates and potential causes. Methods: We use data from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE)-AD study to examine the relationship of three measures of burden among AD caregivers to both patient and caregiver sociodemographic characteristics, measures of patients’ cognitive status, psychiatric and behavioral symptoms, functional abilities, quality of life, and to the intensity of care provided by caregivers. Results: More severe psychiatric and behavioral problems and decreased patient quality of life, as well as lower functional abilities were significantly associated with higher levels of burden and depression among caregivers at baseline. Correaltion of six six-month changes showed that relative symptom reductions and improvements in quality of life were associated with decreased burden and accounted for most of the explained variance in change of burden. Conclusions: Severity of psychiatric symptoms and behavioral disturbances and patients’ quality of life are the main determinants of caregivers’ perception of burden. Effective interventions targeting these two aspects of the disorder are likely to not only alleviate patient suffering but also promote caregiver well-being. P1-177
NEUROPSYCHIATRIC INVENTORY FOR ALZHEIMER’S DISEASE AND MILD COGNITIVE IMPAIRMENT’S PATIENTS WITH NEW CLASSIFICATION METHODS
Taewan Kim, Jinsuk Kim, Jangjun Lee, Jongwhan Choi, Sangwon Park, Yongkook Cho, Daegu Fatima Hospital, Daegu, Republic of Korea. Contact e-mail: [email protected] Background: Diverse neuropsychiatric symptoms (NPS) may manifest according to AD severity. We try to determine what kinds of symptoms are frequent according to subdivided AD groups than usual. We also would like to verify which symptoms are more correlate with ADL. Methods: We prospective and consecutive recruits 73 AD and MCI patients. MCI was defined with DSM -IV criteria. Probable AD was diagnosed according to NINDS-