Modified ketogenic diet is associated with improved cerebrospinal fluid biomarker profile, cerebral perfusion, and cerebral ketone body uptake in older adults at risk for Alzheimer's disease: a pilot study

被引:144
作者
Neth, Bryan J. [1 ,2 ]
Mintz, Akiva [3 ,4 ]
Whitlow, Christopher [3 ]
Jung, Youngkyoo [3 ]
Sai, Kiran Solingapuram [3 ]
Register, Thomas C. [5 ]
Kellar, Derek [1 ]
Lockhart, Samuel N. [1 ]
Hoscheidt, Siobhan [1 ]
Maldjian, Joseph [3 ,6 ]
Heslegrave, Amanda J. [7 ,8 ]
Blennow, Kaj [9 ,10 ]
Cunnane, Stephen C. [11 ]
Castellano, Christian-Alexandre [11 ]
Zetterberg, Henrik [7 ,8 ,9 ,10 ]
Craft, Suzanne [1 ]
机构
[1] Wake Forest Sch Med, Dept Internal Med, Winston Salem, NC 27157 USA
[2] Mayo Clin, Dept Neurol, Rochester, MN USA
[3] Wake Forest Sch Med, Dept Radiol, Winston Salem, NC 27157 USA
[4] Columbia Univ, Dept Radiol, New York, NY USA
[5] Wake Forest Sch Med, Dept Pathol Comparat Med, Winston Salem, NC 27157 USA
[6] Univ Texas Southwestern Med Ctr Dallas, Dept Radiol, Dallas, TX USA
[7] UCL Queen Sq Inst Neurol, Dept Neurodegenerat Dis, London, England
[8] UCL, UK Dementia Res Inst, London, England
[9] Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Molndal, Sweden
[10] Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, Sweden
[11] Univ Sherbrooke, Res Ctr Aging, Sherbrooke, PQ, Canada
基金
瑞典研究理事会;
关键词
Alzheimer's disease; Mild cognitive impairment; Ketogenic diet; CSF biomarkers; MRI; PET; BLOOD-FLOW; MOUSE MODEL; LOW-CARBOHYDRATE; METABOLISM; COGNITION; DEMENTIA; HYPOMETABOLISM; RESTRICTION; GLUCOSE; OBESITY;
D O I
10.1016/j.neurobiolaging.2019.09.015
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
03 ; 0303 ; 100203 ;
摘要
There is currently no established therapy to treat or prevent Alzheimer's disease. The ketogenic diet supplies an alternative cerebral metabolic fuel, with potential neuroprotective effects. Our goal was to compare the effects of a modified Mediterranean-ketogenic diet (MMKD) and an American Heart Association Diet (AHAD) on cerebrospinal fluid Alzheimer's biomarkers, neuroimaging measures, peripheral metabolism, and cognition in older adults at risk for Alzheimer's. Twenty participants with subjective memory complaints (n = 11) or mild cognitive impairment (n = 9) completed both diets, with 3 participants discontinuing early. Mean compliance rates were 90% for MMKD and 95% for AHAD. All participants had improved metabolic indices following MMKD. MMKD was associated with increased cerebrospinal fluid A beta 42 and decreased tau. There was increased cerebral perfusion and increased cerebral ketone body uptake (C-11-acetoacetate PET, in subsample) following MMKD. Memory performance improved after both diets, which may be due to practice effects. Our results suggest that a ketogenic intervention targeted toward adults at risk for Alzheimer's may prove beneficial in the prevention of cognitive decline. (C) 2019 Published by Elsevier Inc.
引用
收藏
页码:54 / 63
页数:10
相关论文
共 68 条
  • [1] Arterial Spin Labeling Blood Flow MRI: Its Role in the Early Characterization of Alzheimer's Disease
    Alsop, David C.
    Dai, Weiying
    Grossman, Murray
    Detre, John A.
    [J]. JOURNAL OF ALZHEIMERS DISEASE, 2010, 20 (03) : 871 - 880
  • [2] 2018 Alzheimer's disease facts and figures
    不详
    [J]. ALZHEIMERS & DEMENTIA, 2018, 14 (03) : 367 - 425
  • [4] American Diabetes Association, 2010, DIABETES CARE, V33, pS11, DOI DOI 10.2337/dc10-S011
  • [5] Regression Algorithm Correcting for Partial Volume Effects in Arterial Spin Labeling MRI
    Asllani, Iris
    Borogovac, Ajna
    Brown, Truman R.
    [J]. MAGNETIC RESONANCE IN MEDICINE, 2008, 60 (06) : 1362 - 1371
  • [6] Diet Intervention and Cerebrospinal Fluid Biomarkers in Amnestic Mild Cognitive Impairment
    Bayer-Carter, Jennifer L.
    Green, Pattie S.
    Montine, Thomas J.
    VanFossen, Brian
    Baker, Laura D.
    Watson, Stennis
    Bonner, Laura M.
    Callaghan, Maureen
    Leverenz, James B.
    Walter, Brooke K.
    Tsai, Elaine
    Plymate, Stephen R.
    Postupna, Nadia
    Wilkinson, Charles W.
    Zhang, Jing
    Lampe, Johanna
    Kahn, Steven E.
    Craft, Suzanne
    [J]. ARCHIVES OF NEUROLOGY, 2011, 68 (06) : 743 - 752
  • [7] A ketogenic diet improves motor performance but does not affect β-amyloid levels in a mouse model of Alzheimer's Disease
    Beckett, Tina L.
    Studzinski, Christa M.
    Keller, Jeffrey N.
    Murphy, M. Paul
    Niedowicz, Dana M.
    [J]. BRAIN RESEARCH, 2013, 1505 : 61 - 67
  • [8] Low Cerebral Blood Flow is Associated with Lower Memory Function in Metabolic Syndrome
    Birdsill, Alex C.
    Carlsson, Cynthia M.
    Willette, Auriel A.
    Okonkwo, Ozioma C.
    Johnson, Sterling C.
    Xu, Guofan
    Oh, Jennifer M.
    Gallagher, Catherine L.
    Koscik, Rebecca L.
    Jonaitis, Erin M.
    Hermann, Bruce P.
    LaRue, Asenath
    Rowley, Howard A.
    Asthana, Sanjay
    Sager, Mark A.
    Bendlin, Barbara B.
    [J]. OBESITY, 2013, 21 (07) : 1313 - 1320
  • [9] The Past and the Future of Alzheimer's Disease Fluid Biomarkers
    Blennow, Kaj
    Zetterberg, Henrik
    [J]. JOURNAL OF ALZHEIMERS DISEASE, 2018, 62 (03) : 1125 - 1140
  • [10] Mitochondrial biogenesis in the anticonvulsant mechanism of the ketogenic diet
    Bough, Kristopher J.
    Wetherington, Jonathon
    Hassel, Bjornar
    Pare, Jean Francois
    Gawryluk, Jeremy W.
    Greene, James G.
    Shaw, Renee
    Smith, Yoland
    Geiger, Jonathan D.
    Dingledine, Raymond J.
    [J]. ANNALS OF NEUROLOGY, 2006, 60 (02) : 223 - 235