- Email: [email protected]
PREVENTION OF DEMENTIA BY INTENSIVE VASCULAR CARE (PREDIVA): A CLUSTER-RANDOMIZED TRIAL
P342
Podium Presentations: Wednesday, July 27, 2016
WEDNESDAY, JULY 27, 2016 ORAL SESSIONS O4-05 CLINICAL THERAPEUTICS: CLINICAL TRIALS — INNOVATIVE TRIALS O4-05-01
PREVENTION OF DEMENTIA BY INTENSIVE VASCULAR CARE (PREDIVA): A CLUSTERRANDOMIZED TRIAL
Edo Richard1,2, Eric P. Moll van Charante1, Lisa S. Eurelings1, JanWillem van Dalen1, Suzanne A. Ligthart1, Emma F. van Bussel1, Marieke P. Hoevenaar1, Marinus Vermeulen1, Willem A. van Gool1, 1 Academic Medical Center, Amsterdam, Netherlands; 2Radboud University Medical Center, Nijmegen, Netherlands. Contact e-mail: e.richard@amc. uva.nl Background: Observational studies show that cardiovascular and
lifestyle related risk factors are associated with an increased risk of dementia. It is unknown whether targeting these risk factors prevents dementia. In the preDIVA trial we test whether a multicomponent intervention targeting vascular and lifestyle related risk factors could prevent incident dementia. Methods: In an open cluster-randomized controlled clinical trial in primary care, with blind outcome adjudication, 3526 persons (age 70-78 years) were randomized to nurse-led vascular care (1890 participants) or usual care (1636 participants). The planned intervention and follow-up duration were six years. Primary outcomes were cumulative dementia incidence and disability. Main secondary outcomes were incident cardiovascular disease (CVD), mortality and dementia according to subtype. Results: Complete data for the primary outcome were obtained for 3454 persons (98%) after a median follow-up of 6.7 years, yielding 21,341 observed person-years. Dementia occurred in 233/3453 participants (6,7%). During the study 578 participants (16,4%) died. Stroke/TIA occurred in 222/2844 participants (7,8%). Mean blood pressure decreased significantly in both groups, but more in the intervention group than in the control group (D2.5 mmHG, p¼0.02). The effect was largest for participants with grade III hypertension (D6.2 mmHG, p¼0.05). Conclusions: PreDIVA is the largest and longest running RCT ever with incident dementia as primary outcome. The pragmatic primary outcome has resulted in a complete follow-up in a very high percentage of participants. A beneficial effect on blood pressure was recorded throughout the study. The manuscript is under review and results will be presented depending on the review process.
O4-05-02
DIETARY FIBRE AND PROTEIN INTAKE AND ASSOCIATIONS WITH BLOOD AND BRAIN AMYLOID BETA BURDEN IN HEALTHY INDIVIDUALS
Warnakulasuriya M. A. D. B. Fernando1, Stephanie R. Rainey-Smith1, Samantha L. Gardener1, Ralph N. Martins1,2,3,4,5and the Australian Imaging, Biomarker and Lifestyle Flagship Study of Ageing (AIBL) Investigators, 1Edith Cowan University, Perth, Australia; 2Cooperative Research Centre for Mental Health, Melbourne, Australia; 3Sir James McCusker Alzheimer’s Disease Research Unit (Hollywood Private Hospital), Perth, Australia; 4School of Psychiatry and Clinical Neurosciences, University of Western Australia, Perth, Australia; 5AIBL Research Group, Perth and Melbourne, Australia. Contact e-mail: w. [email protected] Background: There have been no studies directly investigating the
relationship between protein, fibre and AD, specifically brain and plasma Ab. This cross sectional study examined whether intake
fibre and protein, are associated with plasma and brain Ab levels using Australian elderly cohort drawn from the larger Australian Imaging, Biomarkers and Lifestyle study of ageing [AIBL] cohort. Methods: The AIBL study is a longitudinal study of 1112 volunteers including healthy controls (HC). Of the baseline 541 HCs completed the Cancer Council of Victoria Food Frequency Questionnaire (CCVFFQ). DNA was isolated from the leucocytes, using Qiagen Midiprep kits, and APOE genotype was determined using polymerase chain reaction amplification and restriction enzyme digest techniques. 162 participants underwent a [11C] Pittsburgh compound-B positron emission tomography (PiB PET) scan. Results: The average age, body mass index and energy intake of participants was 69.84, 26.57 kg/m2 and 1693.06 kCal per day respectively. Mean daily protein and fibre intake was 84.44 and 22.96, respectively. The average Ab1-40, Ab1-42 and PiB PET SUVR was 151.43 and , 33.81 pg ml-1 and 1.41 respectively. When PiB PET SUVR was used as a categorical variable, there was 12.594 higher odds of being PiB PET positive if protein intake was in the lowest intake tertile compared to the highest intake tertile (p < 0.05). Additionally, there was 8.425 higher odds of being PiB PET positive if protein intake was in the middle intake tertile compared to the highest intake tertile (p< 0.01). Conclusions: Study indicates if participants had a higher protein intake, they had a lower odds of having a level of Ab in the brain to categorize them as PiB PET positive. There were no associations between fibre intake, protein intake, and the fibre: protein ratio with Ab level in the plasma or PiB PET SUVR as a continuous score. The study highlights the potential negative impact of low protein intake on brain Ab load. However, longitudinal studies are needed to assess the impact of low protein consumption on risk of AD and related diseases. These results would be of considerable interest to researchers, public health officials and the lay public.
O4-05-03
KETOGENIC DIET EFFECTS ON BRAIN KETONE METABOLISM AND ALZHEIMER’S DISEASE CSF BIOMARKERS
Suzanne Craft1, Bryan J. Neth1, Akiva Mintz1, Kiran Sai1, Nora Shively1, Deborah Dahl1, Laura D. Baker2, Stephen Cunnane3, Thomas C. Register1, H. Donald Gage1, 1Wake Forest School of Medicine, Winston-Salem, NC, USA; 2Wake Forest University Health Sciences, Winston Salem, NC, USA; 3 Universite de Sherbrooke, Sherbrooke, QC, Canada. Contact e-mail: [email protected] Background: Diet is a powerful modulator of brain function. The
ketogenic diet (KD), a very low carbohydrate diet, is remarkably effective in treating refractory epilepsy; 50-70% of patients have >50% seizure reduction and 30% have >90% seizure reduction. Although the mechanisms underlying its effectiveness are not definitively known, reduction of neuronal hyperexcitability and neuroprotective effects of ketones have been demonstrated, as has reduction in AD pathology in rodent models. In small pilot studies, interventions that elevate ketones improve memory in adults with MCI and AD. The present study was undertaken to determine whether elevating ketones with diet affected cerebral bioenergetics and AD biomarkers in cerebrospinal fluid (CSF) in adults at risk for AD due to amnestic mild cognitive impairment (MCI) and metabolic dysregulation (prediabetes). Methods: Adults with MCI and prediabetes (n¼10, mean age¼63.6) consumed a 6-week ketogenic diet (<15g carb per day) and a 6-week low fat diet (<10g fat per day) in random order, separated by a 6-week washout period. Diets were equicaloric with participants’ normal diet. Compliance was verified by measuring plasma ketone levels during intervention.
Podium Presentations: Wednesday, July 27, 2016
WEDNESDAY, JULY 27, 2016 ORAL SESSIONS O4-05 CLINICAL THERAPEUTICS: CLINICAL TRIALS — INNOVATIVE TRIALS O4-05-01
PREVENTION OF DEMENTIA BY INTENSIVE VASCULAR CARE (PREDIVA): A CLUSTERRANDOMIZED TRIAL
Edo Richard1,2, Eric P. Moll van Charante1, Lisa S. Eurelings1, JanWillem van Dalen1, Suzanne A. Ligthart1, Emma F. van Bussel1, Marieke P. Hoevenaar1, Marinus Vermeulen1, Willem A. van Gool1, 1 Academic Medical Center, Amsterdam, Netherlands; 2Radboud University Medical Center, Nijmegen, Netherlands. Contact e-mail: e.richard@amc. uva.nl Background: Observational studies show that cardiovascular and
lifestyle related risk factors are associated with an increased risk of dementia. It is unknown whether targeting these risk factors prevents dementia. In the preDIVA trial we test whether a multicomponent intervention targeting vascular and lifestyle related risk factors could prevent incident dementia. Methods: In an open cluster-randomized controlled clinical trial in primary care, with blind outcome adjudication, 3526 persons (age 70-78 years) were randomized to nurse-led vascular care (1890 participants) or usual care (1636 participants). The planned intervention and follow-up duration were six years. Primary outcomes were cumulative dementia incidence and disability. Main secondary outcomes were incident cardiovascular disease (CVD), mortality and dementia according to subtype. Results: Complete data for the primary outcome were obtained for 3454 persons (98%) after a median follow-up of 6.7 years, yielding 21,341 observed person-years. Dementia occurred in 233/3453 participants (6,7%). During the study 578 participants (16,4%) died. Stroke/TIA occurred in 222/2844 participants (7,8%). Mean blood pressure decreased significantly in both groups, but more in the intervention group than in the control group (D2.5 mmHG, p¼0.02). The effect was largest for participants with grade III hypertension (D6.2 mmHG, p¼0.05). Conclusions: PreDIVA is the largest and longest running RCT ever with incident dementia as primary outcome. The pragmatic primary outcome has resulted in a complete follow-up in a very high percentage of participants. A beneficial effect on blood pressure was recorded throughout the study. The manuscript is under review and results will be presented depending on the review process.
O4-05-02
DIETARY FIBRE AND PROTEIN INTAKE AND ASSOCIATIONS WITH BLOOD AND BRAIN AMYLOID BETA BURDEN IN HEALTHY INDIVIDUALS
Warnakulasuriya M. A. D. B. Fernando1, Stephanie R. Rainey-Smith1, Samantha L. Gardener1, Ralph N. Martins1,2,3,4,5and the Australian Imaging, Biomarker and Lifestyle Flagship Study of Ageing (AIBL) Investigators, 1Edith Cowan University, Perth, Australia; 2Cooperative Research Centre for Mental Health, Melbourne, Australia; 3Sir James McCusker Alzheimer’s Disease Research Unit (Hollywood Private Hospital), Perth, Australia; 4School of Psychiatry and Clinical Neurosciences, University of Western Australia, Perth, Australia; 5AIBL Research Group, Perth and Melbourne, Australia. Contact e-mail: w. [email protected] Background: There have been no studies directly investigating the
relationship between protein, fibre and AD, specifically brain and plasma Ab. This cross sectional study examined whether intake
fibre and protein, are associated with plasma and brain Ab levels using Australian elderly cohort drawn from the larger Australian Imaging, Biomarkers and Lifestyle study of ageing [AIBL] cohort. Methods: The AIBL study is a longitudinal study of 1112 volunteers including healthy controls (HC). Of the baseline 541 HCs completed the Cancer Council of Victoria Food Frequency Questionnaire (CCVFFQ). DNA was isolated from the leucocytes, using Qiagen Midiprep kits, and APOE genotype was determined using polymerase chain reaction amplification and restriction enzyme digest techniques. 162 participants underwent a [11C] Pittsburgh compound-B positron emission tomography (PiB PET) scan. Results: The average age, body mass index and energy intake of participants was 69.84, 26.57 kg/m2 and 1693.06 kCal per day respectively. Mean daily protein and fibre intake was 84.44 and 22.96, respectively. The average Ab1-40, Ab1-42 and PiB PET SUVR was 151.43 and , 33.81 pg ml-1 and 1.41 respectively. When PiB PET SUVR was used as a categorical variable, there was 12.594 higher odds of being PiB PET positive if protein intake was in the lowest intake tertile compared to the highest intake tertile (p < 0.05). Additionally, there was 8.425 higher odds of being PiB PET positive if protein intake was in the middle intake tertile compared to the highest intake tertile (p< 0.01). Conclusions: Study indicates if participants had a higher protein intake, they had a lower odds of having a level of Ab in the brain to categorize them as PiB PET positive. There were no associations between fibre intake, protein intake, and the fibre: protein ratio with Ab level in the plasma or PiB PET SUVR as a continuous score. The study highlights the potential negative impact of low protein intake on brain Ab load. However, longitudinal studies are needed to assess the impact of low protein consumption on risk of AD and related diseases. These results would be of considerable interest to researchers, public health officials and the lay public.
O4-05-03
KETOGENIC DIET EFFECTS ON BRAIN KETONE METABOLISM AND ALZHEIMER’S DISEASE CSF BIOMARKERS
Suzanne Craft1, Bryan J. Neth1, Akiva Mintz1, Kiran Sai1, Nora Shively1, Deborah Dahl1, Laura D. Baker2, Stephen Cunnane3, Thomas C. Register1, H. Donald Gage1, 1Wake Forest School of Medicine, Winston-Salem, NC, USA; 2Wake Forest University Health Sciences, Winston Salem, NC, USA; 3 Universite de Sherbrooke, Sherbrooke, QC, Canada. Contact e-mail: [email protected] Background: Diet is a powerful modulator of brain function. The
ketogenic diet (KD), a very low carbohydrate diet, is remarkably effective in treating refractory epilepsy; 50-70% of patients have >50% seizure reduction and 30% have >90% seizure reduction. Although the mechanisms underlying its effectiveness are not definitively known, reduction of neuronal hyperexcitability and neuroprotective effects of ketones have been demonstrated, as has reduction in AD pathology in rodent models. In small pilot studies, interventions that elevate ketones improve memory in adults with MCI and AD. The present study was undertaken to determine whether elevating ketones with diet affected cerebral bioenergetics and AD biomarkers in cerebrospinal fluid (CSF) in adults at risk for AD due to amnestic mild cognitive impairment (MCI) and metabolic dysregulation (prediabetes). Methods: Adults with MCI and prediabetes (n¼10, mean age¼63.6) consumed a 6-week ketogenic diet (<15g carb per day) and a 6-week low fat diet (<10g fat per day) in random order, separated by a 6-week washout period. Diets were equicaloric with participants’ normal diet. Compliance was verified by measuring plasma ketone levels during intervention.