- Email: [email protected]
Prospective study of mitochondrial DNA copy number and incident dementia in Cache County, Utah
S472
Poster Presentations P3 that yielded an estimate of the ratio of mitochondrial genome copies to nuclear genome copies in buccal cell extracts collected from 3,879 participants at baseline in 1995; low level of mtDNA copy number was defined as the 10th percentile or less. Cox proportional hazards models were used to evaluate associations between mtDNA copy number and risk of incident allcause dementia (n ¼ 492) and dementia subtypes including Alzheimer’s disease with vascular diseases and vascular dementia (n ¼ 110) and Alzheimer’s disease in the absence of vascular disease (n ¼ 279). Covariates included sex, baseline age and APOE genotype. Analyses were stratified by baseline agegroup (above and below 75 years). Results: Low level of mtDNA copy number was associated with an increased risk of incident all-cause dementia in participants aged 75 years and older at baseline (hazard ratio (HR) ¼ 1.70, 95% confidence interval (CI) 1.22-2.39) but not significantly associated in those aged 65-74 (HR ¼ 1.17, 95% CI 0.74-1.84). In the older age group a suggestion of a stronger association was found between low mtDNA copy number and the dementia subgroup consisting of Alzheimer’s disease with vascular diseases and vascular dementia (HR ¼ 2.19, CI ¼ 1.12, 4.31) compared to those with Alzheimer’s disease in the absence of vascular disease (HR ¼ 1.43, 95% CI 0.87-2.36). Conclusions: MtDNA copy number, estimated from PCR-based assays of DNA derived from buccal epithelial cells, may be a useful indicator of global mitochondrial function associated with risk of dementia. Further studies are required to determine whether mitochondrial dysfunction is primarily associated with dementia via vascular vs. non-vascular mechanisms and with late-onset vs. earlier onset dementia.
P3-078
latent process represents the common factor five neuropsychological tests outcomes: MMSE, Isaacs Set test, Benton Visual Retention Test, and parts A and B of the Trail Making Test. Analyses were adjusted on sex, education, socio-professional status, insomnia, depressive symptoms and various cardio-vascular risk factors. Results: In the present study, 167 participants reported to take benzodiazepine at each of the 4 examinations and were defined as chronic users. The chronic use of benzodiazepines was significantly associated with a low cognitive latent level (b ¼ -0,024 p ¼ 0,006). No association was found between chronic use and an acceleration of latent cognitive decline (b*(years old) ¼ 0,005 p ¼ 0,445). Moreover, our model allowed to illustrate the metrological properties of neuropsychological tests by showing the shape of their relation with the latent process (Figure 1). Conclusions: By showing a cross sectional association between use of benzodiazepines and cognition but no association with accelerated cognitive decline, our results suggested that chronic use of benzodiazepines is not a risk factor of cognitive decline in free-dementia elderly population.
P3-077
PROSPECTIVE STUDY OF MITOCHONDRIAL DNA COPY NUMBER AND INCIDENT DEMENTIA IN CACHE COUNTY, UTAH
Ronald G. Munger1, Richard M. Cawthon2, Christopher Corcoran1, JoAnn Tschanz1, Maria Norton1, Ken Smith2, Peter Zandi3, Kathleen WelshBohmer4, 1Utah State University, Logan, UT, USA; 2University of Utah, Salt Lake City, UT, USA; 3Johns Hopkins University, Baltimore, MD, USA; 4 Duke University, Durham, NC, USA. Contact e-mail: [email protected] Background: Mitochondrial dysfunction has been implicated in neurodegenerative disorders but remains poorly understood. Mitochondrial DNA (mtDNA) copy number variation may be a useful indicator of mitochondrial function. Methods: The Cache County Memory Study (CCMS) is a prospective study of Utah men and women aged 65+ years at baseline in 1995. Dementia was assessed by clinical examination at baseline and 3, 7, and 11 years later. Participants demented at baseline were excluded from analyses. MtDNA copy number variation was quantified with a quantitative PCR assay
THE INCIDENCE OF STROKE IS INCREASED AMONG PATIENTS WITH ALZHEIMER’S DISEASE IN THE UNITED KINGDOM, 1988-2009
Nicole L. Baker1, Qing Liu1, H. Michael Arrighi2, Kristen Morris2, Roger A. Bullock3, Michael N. Cook1, 1Pfizer Inc., Collegeville, PA, USA; 2 Janssen Alzheimer Immunotherapy Research & Development, South San Francisco, CA, USA; 3Kingshill Research Centre, Swindon, United Kingdom. Contact e-mail: [email protected] Background: The joint occurrence of stroke and Alzheimer’s disease (AD) is more prevalent than what would be expected, possibly because both diseases may be related to a build up of amyloid proteins in the brain. Although several studies have found that a history of stroke is a risk factor for AD, it is not clear if the occurrence of stroke also is increased following the onset of AD. The purpose of this observational study was to estimate the incidence rate of ischemic and hemorrhagic cerebrovascular events among AD patients and age-sex matched non-AD patients. Methods: A retrospective cohort study was conducted using anonymised electronic medical records from nearly 400 primary practices in the United Kingdom. The study population included AD patients aged 50 years or older and a comparison cohort of randomly-selected age-sex-matched patients without AD. Follow-up for each AD patient began at his/her first record of AD in the electronic medical record. Follow-up for each non-AD patient began on the same date as his/ her respective matched AD patient. All patients were followed until the first of any of the following events: a cerebrovascular event, death, transferral out of the practice, or the last date of data collection from the practice. Results: A total of 13,694 AD patients and 13,694 age-sex-matched non-AD patients were included in this study. AD patients were followed for an average of 2.3 years and non-AD patients were followed for an average of 3.4 years. The incidence of cerebrovascular events among patients with and without AD was 18.3 (95% CI, 16.9-19.9) and 11.7 (95% CI, 10.8-12.8) per 1,000 person years, respectively. Overall, patients with AD had an incidence rate that was 1.6 (95% CI, 1.4-1.8) times that of non-AD patients. The increased incidence rate of cerebrovascular events comparing AD patients to non-AD patients was seen in all age groups. Conclusions: The incidence of cerebrovascular events appears to be elevated after a diagnosis of AD in our study population. Patients with AD and their caregivers should be educated on the signs and symptoms of a stroke and be offered preventative services aimed at reducing the overall risk of stroke.
Poster Presentations P3 that yielded an estimate of the ratio of mitochondrial genome copies to nuclear genome copies in buccal cell extracts collected from 3,879 participants at baseline in 1995; low level of mtDNA copy number was defined as the 10th percentile or less. Cox proportional hazards models were used to evaluate associations between mtDNA copy number and risk of incident allcause dementia (n ¼ 492) and dementia subtypes including Alzheimer’s disease with vascular diseases and vascular dementia (n ¼ 110) and Alzheimer’s disease in the absence of vascular disease (n ¼ 279). Covariates included sex, baseline age and APOE genotype. Analyses were stratified by baseline agegroup (above and below 75 years). Results: Low level of mtDNA copy number was associated with an increased risk of incident all-cause dementia in participants aged 75 years and older at baseline (hazard ratio (HR) ¼ 1.70, 95% confidence interval (CI) 1.22-2.39) but not significantly associated in those aged 65-74 (HR ¼ 1.17, 95% CI 0.74-1.84). In the older age group a suggestion of a stronger association was found between low mtDNA copy number and the dementia subgroup consisting of Alzheimer’s disease with vascular diseases and vascular dementia (HR ¼ 2.19, CI ¼ 1.12, 4.31) compared to those with Alzheimer’s disease in the absence of vascular disease (HR ¼ 1.43, 95% CI 0.87-2.36). Conclusions: MtDNA copy number, estimated from PCR-based assays of DNA derived from buccal epithelial cells, may be a useful indicator of global mitochondrial function associated with risk of dementia. Further studies are required to determine whether mitochondrial dysfunction is primarily associated with dementia via vascular vs. non-vascular mechanisms and with late-onset vs. earlier onset dementia.
P3-078
latent process represents the common factor five neuropsychological tests outcomes: MMSE, Isaacs Set test, Benton Visual Retention Test, and parts A and B of the Trail Making Test. Analyses were adjusted on sex, education, socio-professional status, insomnia, depressive symptoms and various cardio-vascular risk factors. Results: In the present study, 167 participants reported to take benzodiazepine at each of the 4 examinations and were defined as chronic users. The chronic use of benzodiazepines was significantly associated with a low cognitive latent level (b ¼ -0,024 p ¼ 0,006). No association was found between chronic use and an acceleration of latent cognitive decline (b*(years old) ¼ 0,005 p ¼ 0,445). Moreover, our model allowed to illustrate the metrological properties of neuropsychological tests by showing the shape of their relation with the latent process (Figure 1). Conclusions: By showing a cross sectional association between use of benzodiazepines and cognition but no association with accelerated cognitive decline, our results suggested that chronic use of benzodiazepines is not a risk factor of cognitive decline in free-dementia elderly population.
P3-077
PROSPECTIVE STUDY OF MITOCHONDRIAL DNA COPY NUMBER AND INCIDENT DEMENTIA IN CACHE COUNTY, UTAH
Ronald G. Munger1, Richard M. Cawthon2, Christopher Corcoran1, JoAnn Tschanz1, Maria Norton1, Ken Smith2, Peter Zandi3, Kathleen WelshBohmer4, 1Utah State University, Logan, UT, USA; 2University of Utah, Salt Lake City, UT, USA; 3Johns Hopkins University, Baltimore, MD, USA; 4 Duke University, Durham, NC, USA. Contact e-mail: [email protected] Background: Mitochondrial dysfunction has been implicated in neurodegenerative disorders but remains poorly understood. Mitochondrial DNA (mtDNA) copy number variation may be a useful indicator of mitochondrial function. Methods: The Cache County Memory Study (CCMS) is a prospective study of Utah men and women aged 65+ years at baseline in 1995. Dementia was assessed by clinical examination at baseline and 3, 7, and 11 years later. Participants demented at baseline were excluded from analyses. MtDNA copy number variation was quantified with a quantitative PCR assay
THE INCIDENCE OF STROKE IS INCREASED AMONG PATIENTS WITH ALZHEIMER’S DISEASE IN THE UNITED KINGDOM, 1988-2009
Nicole L. Baker1, Qing Liu1, H. Michael Arrighi2, Kristen Morris2, Roger A. Bullock3, Michael N. Cook1, 1Pfizer Inc., Collegeville, PA, USA; 2 Janssen Alzheimer Immunotherapy Research & Development, South San Francisco, CA, USA; 3Kingshill Research Centre, Swindon, United Kingdom. Contact e-mail: [email protected] Background: The joint occurrence of stroke and Alzheimer’s disease (AD) is more prevalent than what would be expected, possibly because both diseases may be related to a build up of amyloid proteins in the brain. Although several studies have found that a history of stroke is a risk factor for AD, it is not clear if the occurrence of stroke also is increased following the onset of AD. The purpose of this observational study was to estimate the incidence rate of ischemic and hemorrhagic cerebrovascular events among AD patients and age-sex matched non-AD patients. Methods: A retrospective cohort study was conducted using anonymised electronic medical records from nearly 400 primary practices in the United Kingdom. The study population included AD patients aged 50 years or older and a comparison cohort of randomly-selected age-sex-matched patients without AD. Follow-up for each AD patient began at his/her first record of AD in the electronic medical record. Follow-up for each non-AD patient began on the same date as his/ her respective matched AD patient. All patients were followed until the first of any of the following events: a cerebrovascular event, death, transferral out of the practice, or the last date of data collection from the practice. Results: A total of 13,694 AD patients and 13,694 age-sex-matched non-AD patients were included in this study. AD patients were followed for an average of 2.3 years and non-AD patients were followed for an average of 3.4 years. The incidence of cerebrovascular events among patients with and without AD was 18.3 (95% CI, 16.9-19.9) and 11.7 (95% CI, 10.8-12.8) per 1,000 person years, respectively. Overall, patients with AD had an incidence rate that was 1.6 (95% CI, 1.4-1.8) times that of non-AD patients. The increased incidence rate of cerebrovascular events comparing AD patients to non-AD patients was seen in all age groups. Conclusions: The incidence of cerebrovascular events appears to be elevated after a diagnosis of AD in our study population. Patients with AD and their caregivers should be educated on the signs and symptoms of a stroke and be offered preventative services aimed at reducing the overall risk of stroke.