- Email: [email protected]
The role of lifestyle factors on cognitive decline among older men and women
P326
Poster Presentations: P2
particular, in the late-onset forms of AD, epigenetic alterations might play an important role in the pathophysiology of this disorder. The sulfur compound and dietary supplement S-adenosylmethionine (SAM) has been reported to have cytoprotective and antioxidant properties in the treatment of AD. However, the underlying mechanisms that may explain the cellular protective effects are not fully understood. Methods: H 2 O 2 -induced neuronal toxicity was characterized in SH-SY5Y human neuroblastoma cells by the decrease of cell viability using PrestoBlueÔ assay (Invitrogen) and by the increase o f intracellular reactive oxygen species (ROS) level using DCFH-DA (2’, 7’-dichlorodihydrofluorescin diacetate) assays. Heme oxygenase-1 mRNA expression was assayed by RT-PCR. The immunoblotting analysis is implicated for detecting phosphor-c-Jun, phosphor-AKT, and phosphor-ERK 1/2 expression to check if the anti-apoptotic signal pathways could be activated by H 2 O 2 medium. Results: Pretreatment with 0.01 mg/ml SAM significantly suppressed the H 2 O 2 -induced elevation of intracellular reactive oxygen species (ROS) level by 100% and increased the cell viability by 10% after 24 hours treatment of H 2 O 2 adding. Heme oxygenase-1 (HO-1) gene was up-regulated but phosphor-AKTwas inhibited by pretreatment of 0.01 mg/ml SAM. Conclusions: Our results indicated that SAM may activate HO-1 gene expression to perform the protective effect on neuron through the signal of modulating the phospholation of AKT pathway. The epigenetic alterations on gene expression of SAM treatment may explain that provide a dietary supplement of SAM will be an important part of the interface between the environment and the regulation of gene expression in neuron protection.
P2-198
THE ROLE OF LIFESTYLE FACTORS ON COGNITIVE DECLINE AMONG OLDER MEN AND WOMEN
Sylvie Belleville1, Carol Greenwood2, Marie-Jeanne Kergoat3, Danielle Laurin4, Jose Morais5, Bryna Shatenstein3, Guylaine Ferland3, 1 Research Center, Institut Universitaire de Geriatrie de Montreal, Montreal, Quebec, Canada; 2Baycrest Center, Toronto, Ontario, Canada; 3Institut Universitaire de Geriatrie de Montreal, Montreal, Quebec, Canada; 4 H^ opital du Saint-Sacrement, Quebec, Quebec, Canada; 5MUHC-Royal Victoria Hospital, Montreal, Quebec, Canada. Background: A number of studies have suggested that being physically and cognitively active protects against cognitive decline in older age. However, some have also suggested that the protective effect of lifestyle factors may vary as a function of personal characteristics like sex or education. Unfortunately, most studies have used models that control for these factors rather than directly measure them. The goal of this study was to investigate the association between lifestyle factors and cognitive decline in a group of cognitively-healthy older individuals and assess whether sex was associated with differential levels of association. Methods: Participants were 361 healthy older adults with a mean age of 74 years (range 68 to 82) recruited from the NuAge longitudinal cohort in 2007-2008 (baseline) and followed-up in 2009-2010. The cognitive battery comprised tests of verbal and non-verbal episodic memory, executive functions and processing speed. Cognitive decline was defined as the difference in scores between baseline and follow-up. Associations between education, lifespan level of physical activity, late-life level of physical activity, mental health and physical health (SF-36 scales) and cognition were examined at baseline. General linear modeling then explored the main effects of these variables on decline in task performance over two years, as well as their interaction with sex. Results: Results indicated that higher levels of education and physical activity were associated with better memory and executive functions at baseline. Higher levels of latelife physical activity were associated with lesser decline in verbal memory whereas education was associated with lesser decline in nonverbal memory and executive functions. There was an impact of lifespan physical activity on decline in executive functions but this effect was highly dependent on sex. The protective effect of lifespan physical activity was only apparent in women. Conclusions: These results confirm previous reports suggesting that education and a physically active lifestyle protect from cognitive decline in older age. Our results extend these findings to finer measures of cognitive functioning, particularly memory and executive functions. Furthermore, our study shows that sex modifies the relationship between lifespan physical activity and executive function decline.
P2-199
BODY MASS INDEX AND DEMENTIA IN THE OLDEST-OLD: THE MONZINO 80-PLUS STUDY
Ugo Lucca, Mauro Tettamanti, Mariateresa Garrı, Emma Riva, Alessandro Nobili, Luca Pasina, Carlotta Franchi, Codjo Djade, Angela Recchia, Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy. Background: Whereas midlife overweight has been related to an increased risk of dementia, late-life overweight has been suggested to reduce the risk. Yet, evidence is inconsistent and data are lacking on the relationship between body mass index (BMI) and dementia in the oldest-old, the age segment with the highest dementia prevalence. Objectives: To investigate the risk of developing dementia associated with advanced age BMI in a prospective population-based study of 80-years or older residents in Varese province, Italy (Monzino 80-plus Study). Methods: Individuals’ self-reported or caregiverreported height and weight were used to calculate BMI. Underweight was defined as a BMI <18.5 kg/m2 and overweight-obesity as a BMI 25 kg/m2. Diagnosis of dementia fulfilled DSM-IV criteria. Covariates entered in the fully adjusted logistic and Cox regression models: age, sex, education, current smoking, alcohol consumption, physical activity, depression, diabetes, hypertension, heart failure, atrial fibrillation, myocardial infarction, ictus, COPD. Results: At initial evaluation, data on BMI were available for 1,837 participants (mean age 89.3 years; women: 72.5%). Mean BMI was lower in individuals with dementia (22.6) compared with those without (23.7, p<0.0001). Percentage of underweight individuals was significantly higher in the dementia group (18.5%) compared to the dementia-free group (8.8%, fully adjusted P ¼ 0.0312). Underweight prevalence increased with disease severity: 9.6% in mildly, 18.0% in moderately, 26.3% in severely affected persons (age, sex, education adjusted p <0.0001). Among the 1,035 dementia-free elderly at baseline with at least one follow-up available, the percentage of incident cases in the following 5.5 years was lower among overweight-obese persons (25.9%) compared to normal-weight (31.7%; fully adjusted HR: 0.73, 95% CI: 0.550.97, P ¼ 0.0285) and underweight persons (44.2%; fully adjusted HR: 0.62, 95% CI: 0.41-0.97, P ¼ 0.0365). Baseline continuous BMI was associated with risk of dementia: for each unit increase in BMI the risk of developing dementia decreased 3.5% (fully adjusted HR: 0.966, 95% CI: 0.934-0.997, P ¼ 0.0328). Conclusions: In the oldest-old, higher baseline BMI was associated with a reduced risk of dementia suggesting that the relationship between BMI and dementia may change over time. Underweight could represent a marker of disease severity from the prodromal phase of dementia. P2-200
GROWTH DURING ADOLESCENCE AND RISK OF ALZHEIMER’S DISEASE IN THE ELDERLY
Victoria Moceri1, Michal Schnaider Beeri2, Uri Goldbourt3, 1Sapientia Research, Seattle, Washington, United States; 2Tel Aviv, Tel Aviv, Israel; 3Tel Aviv University, Tel Aviv, Israel. Background: Various anthropometric measures reflective of early-life growth have been investigated for their association with dementia: height, head circumference, leg length, knee height and arm span; but none of these measures are specific to growth during adolescence - a growth period when the brain is still completing maturation that may be critical for later risk of Alzheimer’s disease (AD). We investigated the association between anthropometric measures reflective of growth during adolescence and early-adult life with prevalence of AD in an elderly population. Results: We found the risk of AD to be highest for those whose shoulder breadth was narrower and more equal to their hip breadth; (comparing increasing quartile to 1 st, the odds ratios of 2 nd, 3 rd and 4 th quartile are 0.80, 0.70 & 0.91, respectively), and in those whose scapular skinfold was much thicker then their triceps skinfold (comparing increasing quartile to 1 st, the odds ratios of 2 nd, 3 rd and 4 th quartile are 1.29, 1.64 & 1.36, respectively). Survival bias may be attenuating the association of the 4th quartile. Increasing mortality is associated with increasing subscapular to triceps ratio (comparing to 1 st quartile, the hazards ratios of 2nd, 3rd and 4 th quartile are 1.01, 1.03 & 1.26, respectively). Conclusions: Growth during adolescence and early-adult life is associated with risk of Alzheimer’s disease later in life. Limited growth during adolescence and early-adult life may reflect limited brain reserve.
Poster Presentations: P2
particular, in the late-onset forms of AD, epigenetic alterations might play an important role in the pathophysiology of this disorder. The sulfur compound and dietary supplement S-adenosylmethionine (SAM) has been reported to have cytoprotective and antioxidant properties in the treatment of AD. However, the underlying mechanisms that may explain the cellular protective effects are not fully understood. Methods: H 2 O 2 -induced neuronal toxicity was characterized in SH-SY5Y human neuroblastoma cells by the decrease of cell viability using PrestoBlueÔ assay (Invitrogen) and by the increase o f intracellular reactive oxygen species (ROS) level using DCFH-DA (2’, 7’-dichlorodihydrofluorescin diacetate) assays. Heme oxygenase-1 mRNA expression was assayed by RT-PCR. The immunoblotting analysis is implicated for detecting phosphor-c-Jun, phosphor-AKT, and phosphor-ERK 1/2 expression to check if the anti-apoptotic signal pathways could be activated by H 2 O 2 medium. Results: Pretreatment with 0.01 mg/ml SAM significantly suppressed the H 2 O 2 -induced elevation of intracellular reactive oxygen species (ROS) level by 100% and increased the cell viability by 10% after 24 hours treatment of H 2 O 2 adding. Heme oxygenase-1 (HO-1) gene was up-regulated but phosphor-AKTwas inhibited by pretreatment of 0.01 mg/ml SAM. Conclusions: Our results indicated that SAM may activate HO-1 gene expression to perform the protective effect on neuron through the signal of modulating the phospholation of AKT pathway. The epigenetic alterations on gene expression of SAM treatment may explain that provide a dietary supplement of SAM will be an important part of the interface between the environment and the regulation of gene expression in neuron protection.
P2-198
THE ROLE OF LIFESTYLE FACTORS ON COGNITIVE DECLINE AMONG OLDER MEN AND WOMEN
Sylvie Belleville1, Carol Greenwood2, Marie-Jeanne Kergoat3, Danielle Laurin4, Jose Morais5, Bryna Shatenstein3, Guylaine Ferland3, 1 Research Center, Institut Universitaire de Geriatrie de Montreal, Montreal, Quebec, Canada; 2Baycrest Center, Toronto, Ontario, Canada; 3Institut Universitaire de Geriatrie de Montreal, Montreal, Quebec, Canada; 4 H^ opital du Saint-Sacrement, Quebec, Quebec, Canada; 5MUHC-Royal Victoria Hospital, Montreal, Quebec, Canada. Background: A number of studies have suggested that being physically and cognitively active protects against cognitive decline in older age. However, some have also suggested that the protective effect of lifestyle factors may vary as a function of personal characteristics like sex or education. Unfortunately, most studies have used models that control for these factors rather than directly measure them. The goal of this study was to investigate the association between lifestyle factors and cognitive decline in a group of cognitively-healthy older individuals and assess whether sex was associated with differential levels of association. Methods: Participants were 361 healthy older adults with a mean age of 74 years (range 68 to 82) recruited from the NuAge longitudinal cohort in 2007-2008 (baseline) and followed-up in 2009-2010. The cognitive battery comprised tests of verbal and non-verbal episodic memory, executive functions and processing speed. Cognitive decline was defined as the difference in scores between baseline and follow-up. Associations between education, lifespan level of physical activity, late-life level of physical activity, mental health and physical health (SF-36 scales) and cognition were examined at baseline. General linear modeling then explored the main effects of these variables on decline in task performance over two years, as well as their interaction with sex. Results: Results indicated that higher levels of education and physical activity were associated with better memory and executive functions at baseline. Higher levels of latelife physical activity were associated with lesser decline in verbal memory whereas education was associated with lesser decline in nonverbal memory and executive functions. There was an impact of lifespan physical activity on decline in executive functions but this effect was highly dependent on sex. The protective effect of lifespan physical activity was only apparent in women. Conclusions: These results confirm previous reports suggesting that education and a physically active lifestyle protect from cognitive decline in older age. Our results extend these findings to finer measures of cognitive functioning, particularly memory and executive functions. Furthermore, our study shows that sex modifies the relationship between lifespan physical activity and executive function decline.
P2-199
BODY MASS INDEX AND DEMENTIA IN THE OLDEST-OLD: THE MONZINO 80-PLUS STUDY
Ugo Lucca, Mauro Tettamanti, Mariateresa Garrı, Emma Riva, Alessandro Nobili, Luca Pasina, Carlotta Franchi, Codjo Djade, Angela Recchia, Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy. Background: Whereas midlife overweight has been related to an increased risk of dementia, late-life overweight has been suggested to reduce the risk. Yet, evidence is inconsistent and data are lacking on the relationship between body mass index (BMI) and dementia in the oldest-old, the age segment with the highest dementia prevalence. Objectives: To investigate the risk of developing dementia associated with advanced age BMI in a prospective population-based study of 80-years or older residents in Varese province, Italy (Monzino 80-plus Study). Methods: Individuals’ self-reported or caregiverreported height and weight were used to calculate BMI. Underweight was defined as a BMI <18.5 kg/m2 and overweight-obesity as a BMI 25 kg/m2. Diagnosis of dementia fulfilled DSM-IV criteria. Covariates entered in the fully adjusted logistic and Cox regression models: age, sex, education, current smoking, alcohol consumption, physical activity, depression, diabetes, hypertension, heart failure, atrial fibrillation, myocardial infarction, ictus, COPD. Results: At initial evaluation, data on BMI were available for 1,837 participants (mean age 89.3 years; women: 72.5%). Mean BMI was lower in individuals with dementia (22.6) compared with those without (23.7, p<0.0001). Percentage of underweight individuals was significantly higher in the dementia group (18.5%) compared to the dementia-free group (8.8%, fully adjusted P ¼ 0.0312). Underweight prevalence increased with disease severity: 9.6% in mildly, 18.0% in moderately, 26.3% in severely affected persons (age, sex, education adjusted p <0.0001). Among the 1,035 dementia-free elderly at baseline with at least one follow-up available, the percentage of incident cases in the following 5.5 years was lower among overweight-obese persons (25.9%) compared to normal-weight (31.7%; fully adjusted HR: 0.73, 95% CI: 0.550.97, P ¼ 0.0285) and underweight persons (44.2%; fully adjusted HR: 0.62, 95% CI: 0.41-0.97, P ¼ 0.0365). Baseline continuous BMI was associated with risk of dementia: for each unit increase in BMI the risk of developing dementia decreased 3.5% (fully adjusted HR: 0.966, 95% CI: 0.934-0.997, P ¼ 0.0328). Conclusions: In the oldest-old, higher baseline BMI was associated with a reduced risk of dementia suggesting that the relationship between BMI and dementia may change over time. Underweight could represent a marker of disease severity from the prodromal phase of dementia. P2-200
GROWTH DURING ADOLESCENCE AND RISK OF ALZHEIMER’S DISEASE IN THE ELDERLY
Victoria Moceri1, Michal Schnaider Beeri2, Uri Goldbourt3, 1Sapientia Research, Seattle, Washington, United States; 2Tel Aviv, Tel Aviv, Israel; 3Tel Aviv University, Tel Aviv, Israel. Background: Various anthropometric measures reflective of early-life growth have been investigated for their association with dementia: height, head circumference, leg length, knee height and arm span; but none of these measures are specific to growth during adolescence - a growth period when the brain is still completing maturation that may be critical for later risk of Alzheimer’s disease (AD). We investigated the association between anthropometric measures reflective of growth during adolescence and early-adult life with prevalence of AD in an elderly population. Results: We found the risk of AD to be highest for those whose shoulder breadth was narrower and more equal to their hip breadth; (comparing increasing quartile to 1 st, the odds ratios of 2 nd, 3 rd and 4 th quartile are 0.80, 0.70 & 0.91, respectively), and in those whose scapular skinfold was much thicker then their triceps skinfold (comparing increasing quartile to 1 st, the odds ratios of 2 nd, 3 rd and 4 th quartile are 1.29, 1.64 & 1.36, respectively). Survival bias may be attenuating the association of the 4th quartile. Increasing mortality is associated with increasing subscapular to triceps ratio (comparing to 1 st quartile, the hazards ratios of 2nd, 3rd and 4 th quartile are 1.01, 1.03 & 1.26, respectively). Conclusions: Growth during adolescence and early-adult life is associated with risk of Alzheimer’s disease later in life. Limited growth during adolescence and early-adult life may reflect limited brain reserve.