Flavonoid Intake and MRI Markers of Brain Health in the Framingham Offspring Cohort

ABSTRACT Background Although greater flavonoid intake is associated with a reduced risk of Alzheimer's disease (AD) and related dementias (ADRD), evidence relating dietary flavonoid intake to brain health based on MRI is lacking. Objective The objective of this study was to explore the association between dietary flavonoid intake and MRI measures of brain health, including total brain tissue volume (TBV), white matter hyperintensities volume (WMHV), and hippocampal volume (HV). Methods Eligible subjects included members of the Framingham Heart Study Offspring Cohort who were free of stroke at exam 7 and had at least 1 valid food frequency questionnaire from exams 5, 6, or 7 (n = 2086; mean age at exam 7, 60.6 y). Flavonoid intakes represented the cumulative mean of intakes across the 3 exams and were categorized based on quartiles categories of intake. TBV, WMHV, and HV were assessed at exam 7. Multiple linear regression models were used to examine the cross-sectional association between total and the 6 classes of flavonoids and the 3 aforementioned MRI measures. Results The mean (95% CI) of the WMHV of subjects in the highest quartile category of flavan-3-ols [0.56 (0.52, 0.61)] and flavonoid polymers [0.57 (0.52, 0.61)] intake was significantly smaller relative to that of subjects in the lowest quartile category of flavan-3-ols [0.65 (0.60, 0.71)] and flavonoid polymers [0.66 (0.60, 0.71)] after accounting for important demographic, lifestyle, and clinical factors. Inverse trend associations with WMHV were also seen for flavan-3-ols (P = 0.01) and flavonoid polymers (P = 0.01) as well as for total flavonoids (P = 0.01). TBV and HV were not associated with dietary flavonoid intake following the adjustment for potential confounders. Conclusions Our results contribute to the literature on flavonoids and ADRD as they suggest that higher flavonoid intakes may affect ADRD risk in middle-aged and older adults by reducing WMHV, a marker strongly associated with ADRD.

[1]  L. Beckett,et al.  White matter hyperintensities in vascular contributions to cognitive impairment and dementia (VCID): Knowledge gaps and opportunities , 2019, Alzheimer's & dementia.

[2]  Alberto Pupi,et al.  Mediterranean diet and 3-year Alzheimer brain biomarker changes in middle-aged adults , 2018, Neurology.

[3]  Lisa Mosconi,et al.  Lifestyle and vascular risk effects on MRI-based biomarkers of Alzheimer’s disease: a cross-sectional study of middle-aged adults from the broader New York City area , 2018, BMJ Open.

[4]  K. Yaffe.  Modifiable Risk Factors and Prevention of Dementia: What Is the Latest Evidence? , 2017, JAMA internal medicine.

[5]  Clifford R. Jack,et al.  Mediterranean diet, micronutrients and macronutrients, and MRI measures of cortical thickness , 2017, Alzheimer's & Dementia.

[6]  Joanna M. Wardlaw,et al.  Mediterranean-type diet and brain structural change from 73 to 76 years in a Scottish cohort , 2017, Neurology.

[7]  E. Philippou,et al.  Mediterranean Diet, Cognitive Function, and Dementia: A Systematic Review of the Evidence. , 2016, Advances in nutrition.

[8]  Brian B. Avants,et al.  White matter hyperintensities are more highly associated with preclinical Alzheimer's disease than imaging and cognitive markers of neurodegeneration , 2016, Alzheimer's & dementia.

[9]  Ramachandran S Vasan,et al.  Cohort Profile: The Framingham Heart Study (FHS): overview of milestones in cardiovascular epidemiology. , 2015, International journal of epidemiology.

[10]  Yaakov Stern,et al.  Mediterranean diet and brain structure in a multiethnic elderly cohort , 2015, Neurology.

[11]  Bixente Dilharreguy,et al.  Mediterranean diet and preserved brain structural connectivity in older subjects , 2015, Alzheimer's & Dementia.

[12]  Katherine A. Sauder,et al.  Endothelial function, arterial stiffness and adherence to the 2010 Dietary Guidelines for Americans: a cross-sectional analysis. , 2015, The British journal of nutrition.

[13]  M. Carrillo,et al.  Summary of the evidence on modifiable risk factors for cognitive decline and dementia: A population-based perspective , 2015, Alzheimer's & Dementia.

[14]  Joanna M Wardlaw,et al.  What are White Matter Hyperintensities Made of? , 2015, Journal of the American Heart Association.

[15]  P. Scheltens,et al.  White matter hyperintensities, cognitive impairment and dementia: an update , 2015, Nature Reviews Neurology.

[16]  P. Nederkoorn,et al.  Presence and progression of white matter hyperintensities and cognition , 2014, Neurology.

[17]  W H Tsui,et al.  Mediterranean Diet and Magnetic Resonance Imaging-Assessed Brain Atrophy in Cognitively Normal Individuals at Risk for Alzheimer's Disease. , 2014, The journal of prevention of Alzheimer's disease.

[18]  Helgi B. Schiöth,et al.  Mediterranean diet habits in older individuals: Associations with cognitive functioning and brain volumes , 2013, Experimental Gerontology.

[19]  I. Lang,et al.  Mediterranean Diet, Cognitive Function, and Dementia: A Systematic Review , 2013, Epidemiology.

[20]  A. Vijayakumar,et al.  Comparison of Hippocampal Volume in Dementia Subtypes , 2012, ISRN radiology.

[21]  Roger Tam,et al.  The association between cognitive function and white matter lesion location in older adults: a systematic review , 2012, Alzheimer's & Dementia.

[22]  Charles DeCarli,et al.  Mediterranean diet and white matter hyperintensity volume in the Northern Manhattan Study. , 2012, Archives of neurology.

[23]  Giancarlo Logroscino,et al.  Diet and Alzheimer’s disease risk factors or prevention: the current evidence , 2011, Expert review of neurotherapeutics.

[24]  A. Brickman,et al.  Mediterranean diet and magnetic resonance imaging–assessed cerebrovascular disease , 2011, Annals of neurology.

[25]  E. Rimm,et al.  Habitual intake of flavonoid subclasses and incident hypertension in adults. , 2011, The American journal of clinical nutrition.

[26]  H. Markus,et al.  The clinical importance of white matter hyperintensities on brain magnetic resonance imaging: systematic review and meta-analysis , 2010, BMJ : British Medical Journal.

[27]  O. Chun,et al.  Urinary isoflavones and their metabolites validate the dietary isoflavone intakes in US adults. , 2009, Journal of the American Dietetic Association.

[28]  D. Harvey,et al.  Measures of brain morphology and infarction in the framingham heart study: establishing what is normal , 2005, Neurobiology of Aging.

[29]  T. Bekinschtein,et al.  White matter hyperintensities are significantly associated with cortical atrophy in Alzheimer’s disease , 2004, Journal of Neurology, Neurosurgery & Psychiatry.

[30]  J. Witteman,et al.  Dietary intake of antioxidants and risk of Alzheimer disease. , 2002, JAMA.

[31]  H Adlercreutz,et al.  Intake of dietary phytoestrogens is low in postmenopausal women in the United States: the Framingham study(1-4). , 2001, The Journal of nutrition.

[32]  D. Commenges,et al.  Intake of flavonoids and risk of dementia , 2000, European Journal of Epidemiology.

[33]  Beatty Pg,et al.  National Heart, Lung, and Blood Institute (NHLBI) workshop on the importance of minor histocompatibility antigens in marrow transplantation. September 16-17, 1996; Bethesda, Maryland. , 1997, Experimental hematology.

[34]  D Feskanich,et al.  Reproducibility and validity of food intake measurements from a semiquantitative food frequency questionnaire. , 1993, Journal of the American Dietetic Association.

[35]  G A Colditz,et al.  Reproducibility and validity of an expanded self-administered semiquantitative food frequency questionnaire among male health professionals. , 1992, American journal of epidemiology.

[36]  W. Kannel,et al.  Some health benefits of physical activity. The Framingham Study. , 1979, Archives of internal medicine.

[37]  W. Kannel,et al.  The Framingham Offspring Study. Design and preliminary data. , 1975, Preventive medicine.

[38]  清 黒川.  世界認知症審議会（World Dementia Council）と認知症の課題 , 2016 .