Metabolic Syndrome and Amyloid Accumulation in the Aging Brain.

BACKGROUND Recent studies show links between metabolic syndrome and Alzheimer's disease (AD) neuropathology. Understanding the link between vascular-related health conditions and dementia will help target at risk populations and inform clinical strategies for early detection and prevention of AD. OBJECTIVE To determine whether metabolic syndrome is associated with global cerebral amyloid-β (Aβ) positivity and longitudinal Aβ accumulation. METHODS Prospective study of 165 participants who underwent (11)C-Pittsburgh compound B (PiB) PET neuroimaging to measure Aβ, from June 2005 to May 2016. Metabolic syndrome was defined using the revised Third Adults Treatment Panel of the National Cholesterol Education Program criteria. Participants were classified as PiB+/-. Linear mixed effects models assessed the relationships between baseline metabolic syndrome and PiB status and regional Aβ change over time. RESULTS A total of 165 cognitively normal participants of the Baltimore Longitudinal Study of Aging (BLSA) Neuroimaging substudy, aged 55-92 years (mean baseline age = 76.4 years, 85 participants were male), received an average of 2.5 PET-PiB scans over an average interval of 2.6 (3.08 SD) years between first and last visits. Metabolic syndrome was not associated with baseline PiB positivity or concurrent regional Aβ. Metabolic syndrome was associated with increased rates of Aβ accumulation in superior parietal and precuneus regions over time in the PiB+ group. Elevated fasting glucose and blood pressure showed individual associations with accelerated Aβ accumulation. CONCLUSION Metabolic syndrome was associated with accelerated Aβ accumulation in PiB+ individuals and may be an important factor in the progression of AD pathology.

[1]  L. Ferrucci,et al.  Evidence for brain glucose dysregulation in Alzheimer's disease , 2018, Alzheimer's & Dementia.

[2]  C. Rowe,et al.  Insulin resistance is associated with reductions in specific cognitive domains and increases in CSF tau in cognitively normal adults , 2017, Scientific Reports.

[3]  C. Sánchez-Torres,et al.  Metabolic Syndrome as a Risk Factor for Alzheimer's Disease: Is Aβ a Crucial Factor in Both Pathologies? , 2017, Antioxidants & redox signaling.

[4]  P. Selnes,et al.  White matter hyperintensity microstructure in amyloid dysmetabolism , 2017, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[5]  M. Weiner,et al.  The Role of Cerebrovascular Disease in Amyloid Deposition. , 2016, Journal of Alzheimer's disease : JAD.

[6]  Nicole C. Burns,et al.  Impaired fasting glucose is associated with increased regional cerebral amyloid , 2016, Neurobiology of Aging.

[7]  Zein Al-Atrache,et al.  CHLAMYDIA PNEUMONIAE-INFECTED ASTROCYTES ALTER THEIR EXPRESSION OF ADAM10, BACE1, AND PRESENILIN-1 PROTEASES , 2016, Alzheimer's & Dementia.

[8]  H. Rusinek,et al.  Effects of vascular risk factors, statins, and antihypertensive drugs on PiB deposition in cognitively normal subjects , 2016, Alzheimer's & dementia.

[9]  Alzheimer’s Association,et al.  2016 Alzheimer's disease facts and figures , 2016, Alzheimer's & Dementia.

[10]  Jerry L. Prince,et al.  Individual estimates of age at detectable amyloid onset for risk factor assessment , 2016, Alzheimer's & Dementia.

[11]  Susan M Resnick,et al.  Voxelwise Relationships Between Distribution Volume Ratio and Cerebral Blood Flow: Implications for Analysis of β-Amyloid Images , 2015, The Journal of Nuclear Medicine.

[12]  D. Holtzman,et al.  Hyperglycemia modulates extracellular amyloid-β concentrations and neuronal activity in vivo. , 2015, The Journal of clinical investigation.

[13]  Sterling C. Johnson,et al.  Insulin resistance predicts brain amyloid deposition in late middle-aged adults , 2015, Alzheimer's & Dementia.

[14]  W. M. van der Flier,et al.  The metabolic syndrome in a memory clinic population: Relation with clinical profile and prognosis , 2015, Journal of the Neurological Sciences.

[15]  W. M. van der Flier,et al.  Associations between cerebral small-vessel disease and Alzheimer disease pathology as measured by cerebrospinal fluid biomarkers. , 2014, JAMA Neurology.

[16]  L. Kuller,et al.  Arterial stiffness and β-amyloid progression in nondemented elderly adults. , 2014, JAMA neurology.

[17]  J. Williamson,et al.  Markers of cholesterol transport are associated with amyloid deposition in the brain , 2014, Neurobiology of Aging.

[18]  C. DeCarli,et al.  Associations between serum cholesterol levels and cerebral amyloidosis. , 2014, JAMA neurology.

[19]  Nick C Fox,et al.  Regional variability of imaging biomarkers in autosomal dominant Alzheimer’s disease , 2013, Proceedings of the National Academy of Sciences.

[20]  W. Song,et al.  Molecular links between Alzheimer’s disease and diabetes mellitus , 2013, Neuroscience.

[21]  L. Ferrucci,et al.  Glucose intolerance, insulin resistance, and pathological features of Alzheimer disease in the Baltimore Longitudinal Study of Aging. , 2013, JAMA neurology.

[22]  Florian Auer,et al.  White matter hyperintensities predict amyloid increase in Alzheimer's disease , 2012, Neurobiology of Aging.

[23]  C. Jack,et al.  Cardiovascular risk factors, cortisol, and amyloid-β deposition in Alzheimer's Disease Neuroimaging Initiative , 2012, Alzheimer's & Dementia.

[24]  A. Brickman,et al.  Metabolic syndrome and localization of white matter hyperintensities in the elderly population , 2012, Alzheimer's & Dementia.

[25]  A. Fleisher,et al.  Blood pressure is associated with higher brain amyloid burden and lower glucose metabolism in healthy late middle-age persons , 2012, Neurobiology of Aging.

[26]  S. Monte Contributions of Brain Insulin Resistance and Deficiency in Amyloid-Related Neurodegeneration in Alzheimer’s Disease , 2012, Drugs.

[27]  M. Folstein,et al.  Clinical diagnosis of Alzheimer's disease: Report of the NINCDS—ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease , 2011, Neurology.

[28]  S. Resnick,et al.  In vivo human amyloid imaging. , 2011, Current Alzheimer research.

[29]  S. Resnick,et al.  Amyloid imaging and memory change for prediction of cognitive impairment , 2011, Alzheimer's Research & Therapy.

[30]  J. Rutledge,et al.  The vascular contribution to Alzheimer's disease. , 2010, Clinical science.

[31]  Daniele Sancarlo,et al.  Metabolic-cognitive syndrome: A cross-talk between metabolic syndrome and Alzheimer's disease , 2010, Ageing Research Reviews.

[32]  S. Kanba,et al.  Insulin resistance is associated with the pathology of Alzheimer disease , 2010, Neurology.

[33]  L. Ferrucci,et al.  Longitudinal cognitive decline is associated with fibrillar amyloid-beta measured by [11C]PiB , 2010, Neurology.

[34]  C. Jack,et al.  Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade , 2010, The Lancet Neurology.

[35]  D. Perl Neuropathology of Alzheimer's disease. , 2010, The Mount Sinai journal of medicine, New York.

[36]  Daniele Sancarlo,et al.  Metabolic syndrome and cognitive impairment: current epidemiology and possible underlying mechanisms. , 2010, Journal of Alzheimer's disease : JAD.

[37]  David R. Hunter,et al.  mixtools: An R Package for Analyzing Mixture Models , 2009 .

[38]  D. Hunter,et al.  mixtools: An R Package for Analyzing Mixture Models , 2009 .

[39]  Berislav V. Zlokovic,et al.  Neurovascular mechanisms and blood–brain barrier disorder in Alzheimer’s disease , 2009, Acta Neuropathologica.

[40]  P. Barberger‐Gateau,et al.  Metabolic Syndrome and Risk for Incident Alzheimer's Disease or Vascular Dementia , 2009, Diabetes Care.

[41]  Olga Pletnikova,et al.  Effect of infarcts on dementia in the Baltimore longitudinal study of aging , 2008, Annals of neurology.

[42]  R. Carare,et al.  Perivascular drainage of amyloid-beta peptides from the brain and its failure in cerebral amyloid angiopathy and Alzheimer's disease. , 2008, Brain pathology.

[43]  Brian B. Avants,et al.  Symmetric diffeomorphic image registration with cross-correlation: Evaluating automated labeling of elderly and neurodegenerative brain , 2008, Medical Image Anal..

[44]  R. Carare,et al.  SYMPOSIUM: Clearance of Aβ from the Brain in Alzheimer's Disease: Perivascular Drainage of Amyloid‐β Peptides from the Brain and Its Failure in Cerebral Amyloid Angiopathy and Alzheimer's Disease , 2007 .

[45]  S. Resnick,et al.  Longitudinal Changes in Cerebral Blood Flow in the Older Hypertensive Brain , 2007, Stroke.

[46]  Yun Zhou,et al.  Using a reference tissue model with spatial constraint to quantify [11C]Pittsburgh compound B PET for early diagnosis of Alzheimer's disease , 2007, NeuroImage.

[47]  K. Yaffe Metabolic Syndrome and Cognitive Disorders: Is the Sum Greater Than Its Parts? , 2007, Alzheimer disease and associated disorders.

[48]  Ira Driscoll,et al.  Impact of Alzheimer's pathology on cognitive trajectories in nondemented elderly , 2006, Annals of neurology.

[49]  Alyssa A. Gamaldo,et al.  Effect of a clinical stroke on the risk of dementia in a prospective cohort , 2006, Neurology.

[50]  M. Laakso,et al.  Association of metabolic syndrome with Alzheimer disease , 2006, Neurology.

[51]  Anders M. Dale,et al.  An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest , 2006, NeuroImage.

[52]  S. Grundy,et al.  The metabolic syndrome , 2003, The Lancet.

[53]  R. Petersen Mild cognitive impairment as a diagnostic entity , 2004, Journal of internal medicine.

[54]  J. Schneider,et al.  Cerebral infarctions and the likelihood of dementia from Alzheimer disease pathology , 2004, Neurology.

[55]  Matthew P. Frosch,et al.  Insulin-degrading enzyme regulates the levels of insulin, amyloid β-protein, and the β-amyloid precursor protein intracellular domain in vivo , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[56]  B. Winblad,et al.  Pulse Pressure and Risk of Alzheimer Disease in Persons Aged 75 Years and Older: A Community-Based, Longitudinal Study , 2003, Stroke.

[57]  Willem Hendrik Gispen,et al.  Cognition and synaptic plasticity in diabetes mellitus , 2000, Trends in Neurosciences.

[58]  S. Resnick,et al.  One-year age changes in MRI brain volumes in older adults. , 2000, Cerebral cortex.

[59]  P. Hof,et al.  The neuropathological changes associated with normal brain aging. , 1996, Histology and histopathology.

[60]  C. Grady,et al.  Brain metabolic function in older men with chronic essential hypertension. , 1995, The journals of gerontology. Series A, Biological sciences and medical sciences.

[61]  Y. Benjamini,et al.  Controlling the false discovery rate: a practical and powerful approach to multiple testing , 1995 .

[62]  R. Reitan Trail Making Test: Manual for Administration and Scoring , 1992 .

[63]  I. Rossman,et al.  Normal Human Aging: The Baltimore Longitudinal Study of Aging , 1986 .

[64]  David Arenberg,et al.  Normal Human Aging: The Baltimore Longitudinal Study on Aging , 1984 .

[65]  M. Folstein,et al.  Clinical diagnosis of Alzheimer's disease , 1984, Neurology.

[66]  C. Patlak,et al.  Drainage of interstitial fluid from different regions of rat brain. , 1984, The American journal of physiology.

[67]  J. R. Wilson,et al.  Cognitive Abilities: Use of Family Data as a Control to Assess Sex and Age Differences in Two Ethnic Groups , 1975, International journal of aging & human development.

[68]  John C. DeFries,et al.  Near Identity of Cognitive Structure in Two Ethnic Groups , 1974, Science.

[69]  Brodie Hughes,et al.  MISSILE WOUNDS OF THE BRAIN A Study of Psychological Deficits , 1970 .

[70]  Arthur L. Benton,et al.  Differential behavioral effects in frontal lobe disease , 1968 .