Abstract
Objectives
The association between cognitive function and cholesterol levels is poorly understood and inconsistent results exist among the elderly. The purpose of this study is to investigate the association of cholesterol level with cognitive performance among Chinese elderly.
Design
A cross-sectional study was implemented in 2012 and data were analyzed using generalized additive models, linear regression models and logistic regression models.
Setting
Community-based setting in eight longevity areas in China.
Subjects
A total of 2000 elderly aged 65 years and over (mean 85.8±12.0 years) participated in this study.
Measurements
Total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) concentration were determined and cognitive impairment was defined as Mini-Mental State Examination (MMSE) score≤23.
Results
There was a significant positive linear association between TC, TG, LDL-C, HDL-C and MMSE score in linear regression models. Each 1 mmol/L increase in TC, TG, LDL-C and HDL-C corresponded to a decreased risk of cognitive impairment in logistic regression models. Compared with the lowest tertile, the highest tertile of TC, LDL-C and HDL-C had a lower risk of cognitive impairment. The adjusted odds ratios and 95% CI were 0.73(0.62–0.84) for TC, 0.81(0.70–0.94) for LDL-C and 0.81(0.70–0.94) for HDL-C. There was no gender difference in the protective effects of high TC and LDL-C levels on cognitive impairment. However, for high HDL-C levels the effect was only observed in women. High TC, LDL-C and HDL-C levels were associated with lower risk of cognitive impairment in the oldest old (aged 80 and older), but not in the younger elderly (aged 65 to 79 years).
Conclusions
These findings suggest that cholesterol levels within the high normal range are associated with better cognitive performance in Chinese elderly, specifically in the oldest old. With further validation, low cholesterol may serve a clinical indicator of risk for cognitive impairment in the elderly.
Similar content being viewed by others
References
Jia J, Zhou A, Wei C, et al. The prevalence of mild cognitive impairment and its etiological subtypes in elderly Chinese. Alzheimers Dement 2014; 10:439–447.
Jia J, Wang F, Wei C, et al. The prevalence of dementia in urban and rural areas of China. Alzheimers Dement 2014;10: 1–9.
Muldoon MF, Flory JD, Ryan CM. Serum cholesterol, the brain, and cognitive functioning. Neuropsychology of Cardiovascular Disease. Mahwah, NJ; 2001:37–59.
Helzner EP, Luchsinger JA, Scarmeas N, et al. Contribution of vascular risk factors to the progression in Alzheimer disease. Arch Neurol 2009;66:343–348
Rantanen KK, Strandberg AY, Pitkälä K, et al. Cholesterol in midlife increases the risk of Alzheimer’s disease during an up to 43-year follow-up. Eur Geriatr Med, 2014.
Yaffe K, Barrett-Connor E, Lin F, et al. Serum lipoprotein levels, statin use, and cognitive function in older women. Arch Neurol-Chicago 2002;59: 378–384.
Feng L, Chong MS, Lim WS, et al. Tea for Alzheimer Prevention. J Prev Alz Dis 2015;2:136–141.
Yasuno F, Tanimukai S, Sasaki M, et al. Association between cognitive function and plasma lipids of the elderly after controlling for apolipoprotein E genotype. Am J Geriat Psychiat 2012; 20: 574–583.
Reitz C, Luchsinger J, Tang MX, et al. Impact of plasma lipids and time on memory performance in healthy elderly without dementia. Neurology 2005; 64:1378–1383.
Tukiainen TP, Jylänki VP, Mäkinen O, et al. Mild cognitive impairment associates with concurrent decreases in serum cholesterol and cholesterol-related lipoprotein subclasses. J Nutr Health Aging 2012; 16: 631–635
Stewart R, White LR, Xue QL, et al. Twenty-six-year change in total cholesterol levels and incident dementia: the Honolulu-Asia Aging Study. Arch Neurol 2007;64:103–107.
Yin ZX, Shi XM, Kraus VB, et al. High normal plasma triglycerides are associated with preserved cognitive function in Chinese oldest-old. Age Ageing 2012; 41:600–606.
Kuusisto J, Koivisto K, Mykkänen L, et al. Association between features of the insulin resistance syndrome and Alzheimer’s disease independently of apolipoprotein E4 phenotype: cross sectional population based study. BMJ 1997, 315(7115): 1045–1049.
Piguet O, Grayson D A, Creasey H, et al. Vascular risk factors, cognition and dementia incidence over 6 years in the Sydney Older Persons Study. Neuroepidemiology 2003; 22: 165–171.
Elias P K, Elias M F, D’Agostino R B, et al. Serum cholesterol and cognitive performance in the Framingham Heart Study. Psychosomatic medicine 2005; 67: 24–30.
van Vliet P. Cholesterol and late-life cognitive decline. Journal of Alzheimer’s Disease 2012; 30: S147–S162.
Yi Zeng. Towards deeper research and better policy for healthy aging–using the unique data of Chinese Longitudinal Healthy Longevity Survey. China Economic J 2012; 5:131–149.
Yin ZX, Shi XM, Kraus VB, et al. Gender-dependent association of body mass index and waist circumference with disability in the Chinese oldest old. Obesity, 2014. 22:1918–1925.
Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972; 18:499–502.
Folstein MF, Folstein SE, McHugh PR, et al. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J. Psychiatr. Res 1975;12: 189–198
Tombaugh TN, McIntyre NJ. The mini-mental state examination: a comprehensive review. J Am Geriatr Soc 1992;40: 922–935.
National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 2002, 39(S1): S1–266.
Chinese eGFR Investigation Collaboration. Modification and evaluation of MDRD estimating equation for Chinese patients with chronic kidney disease. Chinese Journal of Nephrology 2006; 22:589–595.
Fagan AM, Younkin LH, Morris JC, et al. Differences in the Aβ40/Aβ42 ratio associated with cerebrospinal fluid lipoproteins as a function of apolipoprotein E genotype. Ann Neurol 2000; 48:201–210.
Michikawa M. Cholesterol paradox: is high total or low HDL cholesterol level a risk for Alzheimer’s disease? J Neurosci Res 2003; 72:141–146.
Stuart SA, Robertson JD, Marrion NV, et al. Chronic Pravastatin but Not Atorvastatin Treatment Impairs Cognitive Function in Two Rodent Models of Learning and Memory. PLoS One 2013;8:e75467.
Wagstaff LR, Mitton MW, Arvik B ML, et al. Statin Associated Memory Loss: Analysis of 60 Case Reports and Review of the Literature. Pharmacotherapy 2003; 23: 871–880.
FDA. Drug Safety Communication: Important safety label changes to cholesterol-lowering statin drugs. 2012.
Zhang Y, Protogerou AD, Iaria P, et al. Prognosis in the hospitalized very elderly: The PROTEGER study. Int J Cardiol 2013; 168:2714–2719.
Schupf N, Costa R, Luchsinger J, et al. Relationship between plasma lipids and all-cause mortality in nondemented elderly. J Am Geriatr Soc 2005; 53:219–226.
Fiorenza AM, Branchi A, Sommariva D. Serum lipoprotein profile in patients with cancer. A comparison with non-cancer subjects. Int J Clin Lab Res 2000;30:141–145.
Hu P, Seeman TE, Harris TB, et al. Does inflammation or undernutrition explain the low cholesterol–mortality association in high-functioning older persons? MacArthur Studies of Successful Aging. J Am Geriatr Soc 2003;51:80–84.
La Rue A, Koehler K M, Wayne S J, et al. Nutritional status and cognitive functioning in a normally aging sample: a 6-y reassessment. Am J Clin Nutr 1997; 65: 20–29.
Otsuka R, Kato Y, Nishita Y, et al. Cereal intake increases and dairy products decrease risk of cognitive decline among elderly female Japanese. J Prev Alz Dis. 2014;1(3):160–167.
Subhan F, Khan I, Arif R, et al. Serum lipid profile as an indicator of the severity of liver damage in cirrhotic patient. Rawal Medical Journal, 2012, 37: 387–389.
Fan QW, Yu W, Gong JS, et al. Cholesterol-dependent modulation of dendrite outgrowth and microtubule stability in cultured neurons. J Neurochem 2002; 80:178–190.
Koudinov AR, Koudinova NV. Essential role for cholesterol in synaptic plasticity and neuronal degeneration. Faseb J 2001;15:1858–1860.
Michikawa M, Yanagisawa K. Inhibition of cholesterol production but not of nonsterol isoprenoid products induces neuronal cell death. J Neurochem 1999; 72:2278–2285.
D.H. Mauch, K. Nagler, S. Schumacher, et al. CNS synaptogenesis promoted by glia-derived cholesterol. Science 2001;294: 1354–1357.
Oliver MF. Serum cholesterol–the knave of hearts and the joker. Lancet 1981;2:1090–1095.
Koudinov AR, Koudinova NV. Essential role for cholesterol in synaptic plasticity and neuronal degeneration. Faseb J 2001;15:1858–1860.
Traber MG, Kayden HJ. Vitamin E is delivered to cells via the high affinity receptor for low-density lipoprotein. Am J Clin Nutr, 1984, 40: 747–751.
Zlokovic B V. The blood-brain barrier in health and chronic neurodegenerative disorders. Neuron 2008, 57: 178–201.
Netea MG, Demacker PN, Kullberg BJ, et al. Low density lipoprotein receptor-deficient mice are protected against lethal endtoxemia and severe Gram-negative infections. J Clin Invest 1996; 97:1366–1372.
Shor-Posner G, Basit A, Lu Y, et al. Hypocholesterolemia is associated with immune dysfunction in early human immunodeficiency virus-1 infection. JAMA 1993; 94: 515–519.
Derecki NC, Quinnies KM, Kipnis J. Alternatively activated myeloid (M2) cells enhance cognitive function in immune compromised mice. Brain Behav Immun. 2011; 25:379–385.
Saxena, R, Amitabha C. Membrane cholesterol stabilizes the human serotonin receptor. Biochimic Biophysica Acta (BBA)-Biomembranes 2012; 1818: 2936–2942.
Ramirez MJ, Lai MKP, Tordera RM et al. Serotonergic Therapies for Cognitive Symptoms in Alzheimer’s Disease: Rationale and Current Status. Drugs 2014; 74: 729–736.
Huber, LA, Xu QB, Jurgens G, et al. Correlation of lymphocyte lipid composition membrane micro viscosity and mitogen response in the aged. Eur J Immunol 1991; 21:2761–2765.
Joseph JA. Cholesterol: a two-edged sword in brain aging. Free Radical Bio Med 1997; 22: 455–462.
Vatassery GT, Smith WE, Quach HT, et al. In vitro oxidation of vitamin E, vitamin C, thiols and cholesterol in rat brain mitochondria incubated with free radicals. Neurochem Int 1995;26:527–535.
Knopp RH, Paramsothy P, Retzlaff BM, et al. Gender differences in lipoprotein metabolism and dietary response: basis in hormonal differences and implications for cardiovascular disease. Curr Atheroscler Rep 2005;7:472–479.
Casiglia E, Tikhonoff V, Caffi S, et al. Menopause does not affect blood pressure and risk profile, and menopausal women do not become similar to men. J Hyperten 2008; 26:1983–1992.
Jousilahti P, Vartiainen E, Tuomilehto J, et al. Sex, age, cardiovascular risk factors, and coronary heart disease: a prospective follow-up study of 14786 middle-aged men and women in Finland. Circulation 1999; 99:1165–1172.
Klag MJ, Ford DE, Mead LA, et al. Serum cholesterol in young men and subsequent cardiovascular disease. N Engl J Med 1993; 328:313–318.
Krumholz HM, Seeman TE, Merrill SS, et al. Lack of association between cholesterol and coronary heart disease mortality and morbidity and all-cause mortality in persons older than 70 years. JAMA 1994; 272:1335–1340.
Author information
Authors and Affiliations
Corresponding author
Additional information
These two authors are co-first authors, they made equal contribution to this work.
Rights and permissions
About this article
Cite this article
Lv, YB., Yin, Z.X., Chei, CL. et al. Serum cholesterol levels within the high normal range are associated with better cognitive performance among Chinese elderly. J Nutr Health Aging 20, 280–287 (2016). https://doi.org/10.1007/s12603-016-0701-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12603-016-0701-6