Metabolic Brain Disease

, Volume 32, Issue 4, pp 1089–1097 | Cite as

Sex-specific nonlinear associations between serum lipids and different domains of cognitive function in middle to older age individuals

  • Yanhui Lu
  • Yu An
  • Huanling Yu
  • Fengyuan Che
  • Xiaona Zhang
  • Hongguo Rong
  • Yuandi Xi
  • Rong XiaoEmail author
Original Article


To examine how serum lipids relates to specific cognitive ability domains between the men and women in Chinese middle to older age individuals. A complete lipid panel was obtained from 1444 individuals, ages 50–65, who also underwent a selection of cognitive tests. Participants were 584 men and 860 women from Linyi city, Shandong province. Multiple linear regression analyses examined serum lipids level as quadratic predictors of sex-specific measure of performance in different cognitive domains, which were adjusted for sociodemographic and lifestyle characteristics. In men, a significant quadratic effect of total cholesterol (TC) was identified for Digit Symbol (B = −0.081, P = 0.044) and also quadratic effect of low density lipoprotein-cholesterol (LDL-C) was identified for Trail Making Test B (B = −0.082, P = 0.045). Differently in women, there were significant quadratic associations between high density lipoprotein-cholesterol (HDL-C) and multiple neuropsychological tests. The nonlinear lipid-cognition associations differed between men and women and were specific to certain cognitive domains and might be of potential relevance for prevention and therapy of cognitive decline.


Serum lipids Cholesterol Sex Cognitive performance Different domains Nonlinear associations 


Compliance with ethical standards


The research was supported by the State Key Program of the National Natural Science Foundation of China (Grant No. 81330065).

Conflict of interest

The authors declare that there are no conflicts of interest.


  1. Allinquant B, Clamagirand C, Potier MC (2014) Role of cholesterol metabolism in the pathogenesis of Alzheimer's disease. Curr Opin Clin Nutr Metab Care 17(4):319–323CrossRefPubMedGoogle Scholar
  2. Ancelin ML, Ritchie K (2005) Lifelong endocrine fluctuations and related cognitive disorders. Curr Pharm Des 11(32):4229–4252CrossRefPubMedGoogle Scholar
  3. Ancelin ML, Ripoche E, Dupuy AM, Samieri C, Rouaud O, Berr C et al (2014) Gender-s pecific associations between lipids and cognitive decline in the elderly. Eur Neuropsychopharmacol 24(7):1056–1066CrossRefPubMedGoogle Scholar
  4. Andreano JM, Cahill L (2009) Sex influences on the neurobiology of learning and memory. Learn Mem 16(4):248–266CrossRefPubMedGoogle Scholar
  5. Anstey KJ, Lipnicki DM, Low LF (2008) Cholesterol as a risk factor for dementia and cognitive decline: a systematic review of prospective studies with meta-analysis. Am J Geriatr Psychiatry 16(5):343–354CrossRefPubMedGoogle Scholar
  6. Artero S, Ancelin ML, Portet F, Dupuy A, Berr C, Dartigues JF et al (2008) Risk profiles for mild cognitive impairment and progression to dementia are gender specific. J Neurol Neurosurg Psychiatry 79(9):979–984CrossRefPubMedGoogle Scholar
  7. Braak, E., Griffing, K., Arai, K., Bohl, J., Bratzke, H., & Braak, H. (1999) Neuropathology of Alzheimer's disease: what is new since a. Alzheimer? Eur Arch Psychiatry Clin Neurosci 249 Suppl 3, 14-22.Google Scholar
  8. Cankurtaran M, Yavuz BB, Halil M, Dagli N, Cankurtaran ES, Ariogul S (2005) Are serum lipid and lipoprotein levels related to dementia? Arch Gerontol Geriatr 41(1):31–39CrossRefPubMedGoogle Scholar
  9. Casiglia E, Tikhonoff V, Caffi S, Bascelli A, Schiavon L, Guidotti F et al (2008) Menopause does not affect blood pressure and risk profile, and menopausal women do not become similar to men. J Hypertens 26(10):1983–1992CrossRefPubMedGoogle Scholar
  10. Dai XY, Ryan JJ, Paolo AM, Harrington RG (1990) Factor analysis of the mainland Chinese version of the Wechsler adult intelligence scale (WAIS-RC) in a brain-damaged sample. Int J Neurosci 55(2–4):107–111CrossRefPubMedGoogle Scholar
  11. Elias PK, Elias MF, D'Agostino RB, Sullivan LM, Wolf PA (2005) Serum cholesterol and cognitive performance in the Framingham heart study. Psychosom Med 67(1):24–30CrossRefPubMedGoogle Scholar
  12. Giedd JN, Snell JW, Lange N, Rajapakse JC, Casey BJ, Kozuch PL et al (1996) Quantitative magnetic resonance imaging of human brain development: ages 4-18. Cereb Cortex 6(4):551–560CrossRefPubMedGoogle Scholar
  13. Helzner EP, Luchsinger JA, Scarmeas N, Cosentino S, Brickman AM, Glymour MM et al (2009) Contribution of vascular risk factors to the progression in Alzheimer disease. Arch Neurol 66(3):343–348CrossRefPubMedPubMedCentralGoogle Scholar
  14. Henderson VW, Guthrie JR, Dennerstein L (2003) Serum lipids and memory in a population based cohort of middle age women. J Neurol Neurosurg Psychiatry 74(11):1530–1535CrossRefPubMedPubMedCentralGoogle Scholar
  15. Knopp RH, Paramsothy P, Retzlaff BM, Fish B, Walden C, Dowdy A et al (2005) Gender differences in lipoprotein metabolism and dietary response: basis in hormonal differences and implications for cardiovascular disease. Current Atherosclerosis Reports 7(6):472–479CrossRefPubMedGoogle Scholar
  16. Kolovou GD, Anagnostopoulou KK, Damaskos DS, Bilianou HI, Mihas C, Milionis HJ et al (2009) Gender differences in the lipid profile of dyslipidemic subjects. European Journal of Internal Medicine 20(2):145–151CrossRefPubMedGoogle Scholar
  17. Lesser GT, Haroutunian V, Purohit DP, Schnaider BM, Schmeidler J, Honkanen L et al (2009) Serum lipids are related to Alzheimer's pathology in nursing home residents. Dement Geriatr Cogn Disord 27(1):42–49CrossRefPubMedPubMedCentralGoogle Scholar
  18. Liao LM, Zhou LX, Le HB, Yin JJ, Ma SH (2012) Spatial working memory dysfunction in minimal hepatic encephalopathy: an ethology and BOLD-fMRI study. Brain Res 1445:62–72CrossRefPubMedGoogle Scholar
  19. Lu J, Li D, Li F, Zhou A, Wang F, Zuo X et al (2011) Montreal cognitive assessment in detecting cognitive impairment in Chinese elderly individuals: a population-based study. J Geriatr Psychiatry Neurol 24(4):184–190CrossRefPubMedGoogle Scholar
  20. Lv YB, Yin ZX, Chei CL, Brasher MS, Zhang J, Kraus VB et al (2016) Serum cholesterol levels within the high normal range are associated with better cognitive performance among Chinese elderly. Journal of Nutrition Health & Aging 20(3):280–287CrossRefGoogle Scholar
  21. Ma WW, Li CQ, Yu HL, Zhang DD, Xi YD, Han J et al (2015a) The oxysterol 27-hydroxycholesterol increases oxidative stress and regulate Nrf2 signaling pathway in astrocyte cells. Neurochem Res 40(4):758–766CrossRefPubMedGoogle Scholar
  22. Ma J, Zhang Y, Guo Q (2015b) Comparison of vascular cognitive impairment--no dementia by multiple classification methods. Int J Neurosci 125(11):823–830CrossRefPubMedGoogle Scholar
  23. McGuinness B, Craig D, Bullock R, Passmore P (2016) Statins for the prevention of dementia. Cochrane Database Syst Rev 1:D3160Google Scholar
  24. Mielke MM, Xue QL, Zhou J, Chaves PH, Fried LP, Carlson MC (2008) Baseline serum cholesterol is selectively associated with motor speed and not rates of cognitive decline: the Women's Health and aging study II. J Gerontol A Biol Sci Med Sci 63(6):619–624CrossRefPubMedPubMedCentralGoogle Scholar
  25. Morley JE, Banks WA (2010) Lipids and cognition. Journal of Alzheimers Disease 20(3):737–747CrossRefGoogle Scholar
  26. Moroney JT, Tang MX, Berglund L, Small S, Merchant C, Bell K et al (1999) Low-density lipoprotein cholesterol and the risk of dementia with stroke. JAMA 282(3):254–260CrossRefPubMedGoogle Scholar
  27. Muldoon MF, Ryan CM, Sereika SM, Flory JD, Manuck SB (2004) Randomized trial of the effects of simvastatin on cognitive functioning in hypercholesterolemic adults. Am J Med 117(11):823–829CrossRefPubMedGoogle Scholar
  28. Neufang S, Specht K, Hausmann M, Gunturkun O, Herpertz-Dahlmann B, Fink GR et al (2009) Sex differences and the impact of steroid hormones on the developing human brain. Cereb Cortex 19(2):464–473CrossRefPubMedGoogle Scholar
  29. Pfrieger FW, Ungerer N (2011) Cholesterol metabolism in neurons and astrocytes. Prog Lipid Res 50(4):357–371CrossRefPubMedGoogle Scholar
  30. Polk DM, Naqvi TZ (2005) Cardiovascular disease in women: sex differences in presentation, risk factors, and evaluation. Curr Cardiol Rep 7(3):166–172CrossRefPubMedGoogle Scholar
  31. Ravnskov U, Diamond DM, Hama R, Hamazaki T, Hammarskjold B, Hynes N et al (2016) Lack of an association or an inverse association between low-density-lipoprotein cholesterol and mortality in the elderly: a systematic review. BMJ Open 6(6):e10401CrossRefGoogle Scholar
  32. Reitz C, Luchsinger J, Tang MX, Manly J, Mayeux R (2005) Impact of plasma lipids and time on memory performance in healthy elderly without dementia. Neurology 64(8):1378–1383CrossRefPubMedPubMedCentralGoogle Scholar
  33. Reitz C, Tang MX, Manly J, Schupf N, Mayeux R, Luchsinger JA (2008) Plasma lipid levels in the elderly are not associated with the risk of mild cognitive impairment. Dement Geriatr Cogn Disord 25(3):232–237CrossRefPubMedPubMedCentralGoogle Scholar
  34. Reynolds CA, Gatz M, Prince JA, Berg S, Pedersen NL (2010) Serum lipid levels and cognitive change in late life. J Am Geriatr Soc 58(3):501–509CrossRefPubMedPubMedCentralGoogle Scholar
  35. Shepardson NE, Shankar GM, Selkoe DJ (2011) Cholesterol level and statin use in Alzheimer disease: II. Review of human trials and recommendations. Arch Neurol 68(11):1385–1392CrossRefPubMedPubMedCentralGoogle Scholar
  36. Sowers MR, Symons JP, Jannausch ML, Chu J, Kardia SR (2006) Sex steroid hormone polymorphisms, high-density lipoprotein cholesterol, and apolipoprotein A-1 from the study of Women's Health across the nation (SWAN). Am J Med 119(9 Suppl 1):S61–S68CrossRefPubMedGoogle Scholar
  37. Stewart R, White LR, Xue QL, Launer LJ (2007) Twenty-six-year change in total cholesterol levels and incident dementia: the Honolulu-Asia aging study. Arch Neurol 64(1):103–107CrossRefPubMedGoogle Scholar
  38. Wang C, An Y, Yu H, Feng L, Liu Q, Lu Y et al (2016) Association between exposure to the Chinese famine in different stages of early life and decline in cognitive functioning in adulthood. Front Behav Neurosci 10:146PubMedPubMedCentralGoogle Scholar
  39. Wendell CR, Zonderman AB, Katzel LI, Rosenberger WF, Plamadeala VV, Hosey MM et al (2016) Nonlinear associations between plasma cholesterol levels and neuropsychological function. Neuropsychology 30(8):980–987CrossRefPubMedGoogle Scholar
  40. Yaffe K, Barrett-Connor E, Lin F, Grady D (2002) Serum lipoprotein levels, statin use, and cognitive function in older women. Arch Neurol 59(3):378–384CrossRefPubMedGoogle Scholar
  41. Zagni E, Simoni L, Colombo D (2016) Sex and gender differences in central nervous system-related disorders. Neurosci J 2016:2827090CrossRefPubMedPubMedCentralGoogle Scholar
  42. Zhang J, Muldoon MF, McKeown RE (2004) Serum cholesterol concentrations are associated with visuomotor speed in men: findings from the third National Health and nutrition examination survey, 1988-1994. Am J Clin Nutr 80(2):291–298PubMedGoogle Scholar
  43. Zhang DD, Yu HL, Ma WW, Liu QR, Han J, Wang H et al (2015) 27-Hydroxycholesterol contributes to disruptive effects on learning and memory by modulating cholesterol metabolism in the rat brain. Neuroscience 300:163–173CrossRefPubMedGoogle Scholar
  44. Zhao Q, Guo Q, Li F, Zhou Y, Wang B, Hong Z (2013) The Shape Trail test: application of a new variant of the Trail making test. PLoS One 8(2):e57333CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Yanhui Lu
    • 1
    • 2
  • Yu An
    • 1
  • Huanling Yu
    • 1
  • Fengyuan Che
    • 3
  • Xiaona Zhang
    • 1
  • Hongguo Rong
    • 1
  • Yuandi Xi
    • 1
  • Rong Xiao
    • 1
    Email author
  1. 1.School of Public HealthCapital Medical UniversityBeijingChina
  2. 2.Linyi Mental Health CenterLinyiChina
  3. 3.Linyi People’s HospitalLinyiChina

Personalised recommendations