- Email: [email protected]
Cognitive changes following oophorectomy
Poster Presentations: P4 were heterotopias and demyelination. Conclusions: The diagnosis of AD and its relationship to altered neurodevelopment were confirmed.
P877
research showing cognitive decline post-BSO, but also suggests that verbal memory declines as a function of time since estrogen deprivation.
P4-386
CORRELATES OF SUBJECTIVE AND MILD COGNITIVE IMPAIRMENT
Ramune Grambaite1, Erik Hessen1, Eirik Auning2, Per Selnes3, Dag Aarsland4, Tormod Fladby5, 1Akershus University Hospital, Lørenskog, Norway; 2Akershus University Hospital, Department of Old Age Psychiatry, and University of Oslo, Oslo, Norway; 3University of Oslo Ahus, Lorenskog, Norway; 4Stavanger University Hospital, Stavanger, Norway; 5 Ahus, University of Oslo, Lørenskog, Norway. Contact e-mail: ramune. [email protected]
P4-385
COGNITIVE CHANGES FOLLOWING OOPHORECTOMY
April Au1, Deborah Schwartz1, Amy Finch2, Mary Tierney3, Elizabeth Hampson4, Steven Narod2, Gillian Einstein1, 1University of Toronto, Toronto, Ontario, Canada; 2Women’s College Research Institute, Toronto, Ontario, Canada; 3Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada; 4University of Western Ontario, London, Ontario, Canada. Contact e-mail: [email protected] Background: Epidemiological evidence indicating oophorectomy prior to natural menopause is associated with an increased risk of Alzheimer’s Disease (Rocca et al., 2007) and parkinsonism (Rocca et al., 2008) suggests that estrogen deprivation is implicated in cognitive decline. However, the trajectory of cognitive changes following oophorectomy is poorly understood beyond six months post-surgically (Sherwin, 1988). The purpose of this study was to determine the long-term effects of estrogen deprivation induced by oophorectomy on cognitive functioning, up to ten years post-surgically. Methods: The experimental group comprised of female carriers of the BRCA1/2 mutation who had undergone a bilateral salpingo-oophorectomy (BSO; removal of fallopian tubes and ovaries) between one to seven years ago as prophylaxis against the risk of gynaecological cancers. An agematched control group of healthy women and a BRCA control group comprised of women with a BRCA mutation prior to oophorectomy were also recruited. All women were tested once a year, for three years using a battery of neuropsychological tests assessing spatial and verbal memory, working memory, as well as executive functioning. Urine and saliva samples were taken respectively to determine estrogen levels at the time of testing and apolipoprotein E (APOE) genotype. It was hypothesized that women who have undergone BSO would score lower on measures of verbal memory. Carriers of the APOE E4 allele who had undergone BSO were hypothesized to perform the worst as the E4 allele is associated with an increased vulnerability to Alzheimer’s disease. Results: Results indicate that women with BSO performed significantly worse than age-matched controls on the immediate and delayed recall of the Logical Memory task of the Wechsler Memory Scale. Years since oophorectomy was also negatively correlated to the score on the delayed recall of the RAVLT after controlling for age. Conclusions: Preliminary results suggest that premature estrogen deprivation is associated with a decrement in verbal memory compared to women matched in age and education. Importantly, time since BSO appears to exacerbate the decline of verbal memory independent of age. Results corroborate previous
Background: The concepts subjective (SCI) and mild cognitive impairment (MCI) are used to describe conditions with an increased risk of developing dementia, including Alzheimer’s disease. The study aims to investigate correlates of cognitive complaints and cognitive performance in patients with SCI and MCI. Methods: Seventy patients from a university-hospital based memory clinic, aged 45-79, with a score 2 (n¼23) or 3 (n¼47) on the Global Deterioration Scale were included. Lumbar puncture and neuropsychological examination were performed, and depressive symptoms and cognitive complaints were assessed. Results: Correlation analysis showed that cognitive complaints increased with decreasing cognitive function in SCI and decreased with decreasing cognitive function in MCI. Linear regression models revealed that cognitive complaints were associated with depressive symptoms in both groups of patients, while cognitive performance was associated with CSF Ab42 and P-tau in SCI and with T-tau and P-tau in MCI. Conclusions: These results suggest that depressive symptoms may increase cognitive complaints, while degenerative changes (relating to pathological levels of CSF biomarkers) predict objective cognitive decline in high-risk pre-dementia states.
P4-387
ALZHEIMER’S DISEASE BIOMARKERS AND NORMATIVE COGNITIVE DATA: THE SUPERNORMS APPROACH
Rachel Chasse1, Tammie Benzinger2, Elizabeth Grant1, Nigel Cairns1, Anne Fagan1, John Morris1, Jason Hassenstab1, 1Washington University, St. Louis, St. Louis, Missouri, United States; 2Washington University School of Medicine, St. Louis, Missouri, United States. Contact e-mail: [email protected] Background: Normative cognitive datasets in older populations may be contaminated with individuals who have subtle decline due to preclinical Alzheimer’s disease (AD). Means drawn from these samples may be artificially low, reducing the sensitivity to detect impairment. In this study, we developed a "SuperNorms" database composed of cognitively normal individuals with no biomarker evidence of preclinical AD and tested whether these robust norms improved diagnostic accuracy. Methods: Amyloid imaging (PET PIB), cerebrospinal fluid markers (tau, p-tau, Ab42), and MRI-derived hippocampal volumes from 264 cognitively normal (CDR¼0) participants (ages 65-89) were used to classify individuals as biomarker-negative ("Super-Normal", n¼177) or biomarker-positive ("Preclinical AD", n¼87). Normative data for commonly used cognitive tests (including measures from the Uniform Data Set) were created from the Super-Normal group and both groups combined. These norms were applied to a separate longitudinal sample of participants who enrolled as cognitively normal (CDR¼0) but either progressed to a consistent clinical diagnosis of AD (CDR>0,"Progressors", n¼46) or who never progressed to CDR>0 ("Stable", n¼98). Scores were normalized with both the SuperNormal and combined norms across an average of 9.5 visits per participant. Finally, sensitivity and specificity analyses determined if the Super-Normal database could enhance the detection of cognitive impairment at the time of AD diagnosis and at the visit prior to diagnosis in the Progressors group. Results: The Super-Normal group had reduced variability and was less affected by age than the Preclinical AD group. The Super-Normal group scored better on several cognitive tests, including measures of verbal recall
P877
research showing cognitive decline post-BSO, but also suggests that verbal memory declines as a function of time since estrogen deprivation.
P4-386
CORRELATES OF SUBJECTIVE AND MILD COGNITIVE IMPAIRMENT
Ramune Grambaite1, Erik Hessen1, Eirik Auning2, Per Selnes3, Dag Aarsland4, Tormod Fladby5, 1Akershus University Hospital, Lørenskog, Norway; 2Akershus University Hospital, Department of Old Age Psychiatry, and University of Oslo, Oslo, Norway; 3University of Oslo Ahus, Lorenskog, Norway; 4Stavanger University Hospital, Stavanger, Norway; 5 Ahus, University of Oslo, Lørenskog, Norway. Contact e-mail: ramune. [email protected]
P4-385
COGNITIVE CHANGES FOLLOWING OOPHORECTOMY
April Au1, Deborah Schwartz1, Amy Finch2, Mary Tierney3, Elizabeth Hampson4, Steven Narod2, Gillian Einstein1, 1University of Toronto, Toronto, Ontario, Canada; 2Women’s College Research Institute, Toronto, Ontario, Canada; 3Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada; 4University of Western Ontario, London, Ontario, Canada. Contact e-mail: [email protected] Background: Epidemiological evidence indicating oophorectomy prior to natural menopause is associated with an increased risk of Alzheimer’s Disease (Rocca et al., 2007) and parkinsonism (Rocca et al., 2008) suggests that estrogen deprivation is implicated in cognitive decline. However, the trajectory of cognitive changes following oophorectomy is poorly understood beyond six months post-surgically (Sherwin, 1988). The purpose of this study was to determine the long-term effects of estrogen deprivation induced by oophorectomy on cognitive functioning, up to ten years post-surgically. Methods: The experimental group comprised of female carriers of the BRCA1/2 mutation who had undergone a bilateral salpingo-oophorectomy (BSO; removal of fallopian tubes and ovaries) between one to seven years ago as prophylaxis against the risk of gynaecological cancers. An agematched control group of healthy women and a BRCA control group comprised of women with a BRCA mutation prior to oophorectomy were also recruited. All women were tested once a year, for three years using a battery of neuropsychological tests assessing spatial and verbal memory, working memory, as well as executive functioning. Urine and saliva samples were taken respectively to determine estrogen levels at the time of testing and apolipoprotein E (APOE) genotype. It was hypothesized that women who have undergone BSO would score lower on measures of verbal memory. Carriers of the APOE E4 allele who had undergone BSO were hypothesized to perform the worst as the E4 allele is associated with an increased vulnerability to Alzheimer’s disease. Results: Results indicate that women with BSO performed significantly worse than age-matched controls on the immediate and delayed recall of the Logical Memory task of the Wechsler Memory Scale. Years since oophorectomy was also negatively correlated to the score on the delayed recall of the RAVLT after controlling for age. Conclusions: Preliminary results suggest that premature estrogen deprivation is associated with a decrement in verbal memory compared to women matched in age and education. Importantly, time since BSO appears to exacerbate the decline of verbal memory independent of age. Results corroborate previous
Background: The concepts subjective (SCI) and mild cognitive impairment (MCI) are used to describe conditions with an increased risk of developing dementia, including Alzheimer’s disease. The study aims to investigate correlates of cognitive complaints and cognitive performance in patients with SCI and MCI. Methods: Seventy patients from a university-hospital based memory clinic, aged 45-79, with a score 2 (n¼23) or 3 (n¼47) on the Global Deterioration Scale were included. Lumbar puncture and neuropsychological examination were performed, and depressive symptoms and cognitive complaints were assessed. Results: Correlation analysis showed that cognitive complaints increased with decreasing cognitive function in SCI and decreased with decreasing cognitive function in MCI. Linear regression models revealed that cognitive complaints were associated with depressive symptoms in both groups of patients, while cognitive performance was associated with CSF Ab42 and P-tau in SCI and with T-tau and P-tau in MCI. Conclusions: These results suggest that depressive symptoms may increase cognitive complaints, while degenerative changes (relating to pathological levels of CSF biomarkers) predict objective cognitive decline in high-risk pre-dementia states.
P4-387
ALZHEIMER’S DISEASE BIOMARKERS AND NORMATIVE COGNITIVE DATA: THE SUPERNORMS APPROACH
Rachel Chasse1, Tammie Benzinger2, Elizabeth Grant1, Nigel Cairns1, Anne Fagan1, John Morris1, Jason Hassenstab1, 1Washington University, St. Louis, St. Louis, Missouri, United States; 2Washington University School of Medicine, St. Louis, Missouri, United States. Contact e-mail: [email protected] Background: Normative cognitive datasets in older populations may be contaminated with individuals who have subtle decline due to preclinical Alzheimer’s disease (AD). Means drawn from these samples may be artificially low, reducing the sensitivity to detect impairment. In this study, we developed a "SuperNorms" database composed of cognitively normal individuals with no biomarker evidence of preclinical AD and tested whether these robust norms improved diagnostic accuracy. Methods: Amyloid imaging (PET PIB), cerebrospinal fluid markers (tau, p-tau, Ab42), and MRI-derived hippocampal volumes from 264 cognitively normal (CDR¼0) participants (ages 65-89) were used to classify individuals as biomarker-negative ("Super-Normal", n¼177) or biomarker-positive ("Preclinical AD", n¼87). Normative data for commonly used cognitive tests (including measures from the Uniform Data Set) were created from the Super-Normal group and both groups combined. These norms were applied to a separate longitudinal sample of participants who enrolled as cognitively normal (CDR¼0) but either progressed to a consistent clinical diagnosis of AD (CDR>0,"Progressors", n¼46) or who never progressed to CDR>0 ("Stable", n¼98). Scores were normalized with both the SuperNormal and combined norms across an average of 9.5 visits per participant. Finally, sensitivity and specificity analyses determined if the Super-Normal database could enhance the detection of cognitive impairment at the time of AD diagnosis and at the visit prior to diagnosis in the Progressors group. Results: The Super-Normal group had reduced variability and was less affected by age than the Preclinical AD group. The Super-Normal group scored better on several cognitive tests, including measures of verbal recall