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Late-life body mass index, rapid weight loss, apolipoprotein E ε4 and the risk of cognitive decline and incident dementia

  • Published:
The journal of nutrition, health & aging

Abstract

Objectives

To examine the effect of late-life body mass index (BMI) and rapid weight loss on incident mild cognitive impairment (MCI) and Alzheimer’s disease (AD).

Design

Prospective longitudinal cohort study.

Setting

National Alzheimer’s Coordinating Center (NACC) Uniform Data Set, including 34 past and current National Institute on Aging-funded AD Centers across the United States.

Participants

6940 older adults (n=5061 normal cognition [NC]; n=1879 MCI).

Measurements

BMI (kg/m2) and modified Framingham Stroke Risk Profile (FSRP) score (sex, age, systolic blood pressure, anti-hypertension medication, diabetes mellitus, cigarette smoking, prevalent cardiovascular disease, atrial fibrillation) were assessed at baseline. Cognition and weight were assessed annually.

Results

Multivariable binary logistic regression, adjusting for age, sex, race, education, length of follow-up, and modified FSRP related late-life BMI to risk of diagnostic conversion from NC to MCI or AD and from MCI to AD. Secondary analyses related late-life BMI to diagnostic conversion in the presence of rapid weight loss (>5% decrease in 12 months) and apolipoprotein E (APOE) ε4. During a mean 3.8-year follow-up period, 12% of NC participants converted to MCI or AD and 49% of MCI participants converted to AD. Higher baseline BMI was associated with a reduced probability of diagnostic conversion, such that for each one-unit increase in baseline BMI there was a reduction in diagnostic conversion for both NC (OR=0.977, 95%CI 0.958-0.996, p=0.015) and MCI participants (OR=0.962, 95%CI 0.942-0.983, p<0.001). The protective effect of higher baseline BMI did not persist in the setting of rapid weight loss but did persist when adjusting for APOE ε4.

Conclusions

Higher late-life BMI is associated with a lower risk of incident MCI and AD but is not protective in the presence of rapid weight loss.

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References

  1. Hebert LE, Weuve J, Scherr PA, Evans DA. Alzheimer disease in the United States (2010-2050) estimated using the 2010 census. Neurology; 2013;80(19):1778–83. doi: 10.1212/WNL.0b013e31828726f5.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Yaffe K, Lindquist K, Vittinghoff E, Barnes D, Simonsick EM, Newman A, Satterfield S, Rosano C, Rubin SM, Ayonayon HN, et al. The effect of maintaining cognition on risk of disability and death. Journal of the American Geriatrics Society; 2010;58(5):889–94. doi: 10.1111/j.1532-5415.2010.02818.x.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Schiffczyk C, Romero B, Jonas C, Lahmeyer C, Muller F, Riepe MW. Generic quality of life assessment in dementia patients: a prospective cohort study. BMC neurology; 2010;10:48. doi: 10.1186/1471-2377-10-48.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Sandman PO, Adolfsson R, Nygren C, Hallmans G, Winblad B. Nutritional status and dietary intake in institutionalized patients with Alzheimer’s disease and multiinfarct dementia. Journal of the American Geriatrics Society; 1987;35(1):31–8.

    Article  CAS  PubMed  Google Scholar 

  5. White H, Pieper C, Schmader K. The association of weight change in Alzheimer’s disease with severity of disease and mortality: a longitudinal analysis. Journal of the American Geriatrics Society; 1998;46(10):1223–7.

    Article  CAS  PubMed  Google Scholar 

  6. Gustafson D, Rothenberg E, Blennow K, Steen B, Skoog I. An 18-year followup of overweight and risk of Alzheimer disease. Archives of internal medicine; 2003;163(13):1524–8. doi: 10.1001/archinte.163.13.1524.

    Article  PubMed  Google Scholar 

  7. Nourhashemi F, Deschamps V, Larrieu S, Letenneur L, Dartigues JF, Barberger-Gateau P, Quid PsPA. Body mass index and incidence of dementia: the PAQUID study. Neurology; 2003;60(1):117–9.

    Article  CAS  PubMed  Google Scholar 

  8. Buchman AS, Wilson RS, Bienias JL, Shah RC, Evans DA, Bennett DA. Change in body mass index and risk of incident Alzheimer disease. Neurology; 2005;65(6):892–7. doi: 10.1212/01.wnl.0000176061.33817.90.

    Article  CAS  PubMed  Google Scholar 

  9. Fitzpatrick AL, Kuller LH, Lopez OL, Diehr P, O’Meara ES, Longstreth WT, Jr., Luchsinger JA. Midlife and late-life obesity and the risk of dementia: cardiovascular health study. Archives of neurology; 2009;66(3):336–42. doi: 10.1001/archneurol.2008.582.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Qizilbash N, Gregson J, Johnson ME, Pearce N, Douglas I, Wing K, Evans SJ, Pocock SJ. BMI and risk of dementia in two million people over two decades: a retrospective cohort study. The lancet Diabetes & endocrinology 2015;. doi: 10.1016/S2213-8587(15)00033-9.

    Google Scholar 

  11. Besser LM, Gill DP, Monsell SE, Brenowitz W, Meranus DH, Kukull W, Gustafson DR. Body mass index, weight change, and clinical progression in mild cognitive impairment and Alzheimer disease. Alzheimer disease and associated disorders; 2014;28(1):36–43. doi: 10.1097/WAD.0000000000000005.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Ho AJ, Raji CA, Becker JT, Lopez OL, Kuller LH, Hua X, Lee S, Hibar D, Dinov ID, Stein JL, et al. Obesity is linked with lower brain volume in 700 AD and MCI patients. Neurobiology of aging; 2010;31(8):1326–39. doi: 10.1016/j. neurobiolaging.2010.04.006.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Hughes TF, Borenstein AR, Schofield E, Wu Y, Larson EB. Association between late-life body mass index and dementia: The Kame Project. Neurology; 2009;72(20):1741–6. doi: 10.1212/WNL.0b013e3181a60a58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Yoshitake T, Kiyohara Y, Kato I, Ohmura T, Iwamoto H, Nakayama K, Ohmori S, Nomiyama K, Kawano H, Ueda K, et al. Incidence and risk factors of vascular dementia and Alzheimer’s disease in a defined elderly Japanese population: the Hisayama Study. Neurology; 1995;45(6):1161–8.

    Article  CAS  PubMed  Google Scholar 

  15. Anstey KJ, Cherbuin N, Budge M, Young J. Body mass index in midlife and latelife as a risk factor for dementia: a meta-analysis of prospective studies. Obesity reviews: an official journal of the International Association for the Study of Obesity; 2011;12(5):e426–37. doi: 10.1111/j.1467-789X.2010.00825.x.

    Article  CAS  Google Scholar 

  16. Harris TB, Launer LJ, Madans J, Feldman JJ. Cohort study of effect of being overweight and change in weight on risk of coronary heart disease in old age. Bmj; 1997;314(7097):1791-. doi: 10.1136/bmj.314.7097.1791.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Petkeviciene J, Smalinskiene A, Luksiene DI, Jureniene K, Ramazauskiene V, Klumbiene J, Lesauskaite V. Associations between apolipoprotein E genotype, diet, body mass index, and serum lipids in Lithuanian adult population. PloS one; 2012;7(7):e41525. doi: 10.1371/journal.pone.0041525.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. de Andrade M, Thandi I, Brown S, Gotto A, Jr., Patsch W, Boerwinkle E. Relationship of the apolipoprotein E polymorphism with carotid artery atherosclerosis. American journal of human genetics; 1995;56(6):1379–90.

    PubMed  PubMed Central  Google Scholar 

  19. Matsumura K, Ansai T, Awano S, Hamasaki T, Akifusa S, Takehara T, Abe I, Takata Y. Association of body mass index with blood pressure in 80-year-old subjects. Journal of hypertension; 2001;19(12):2165–9.

    Article  CAS  PubMed  Google Scholar 

  20. Corder EH, Saunders AM, Strittmatter WJ, Schmechel DE, Gaskell PC, Small GW, Roses AD, Haines JL, Pericak-Vance MA. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science; 1993;261(5123):921–3.

    Article  CAS  PubMed  Google Scholar 

  21. Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, Seeman T, Tracy R, Kop WJ, Burke G, et al. Frailty in older adults: evidence for a phenotype. The journals of gerontology Series A, Biological sciences and medical sciences; 2001;56(3):M146–56.

    Article  CAS  PubMed  Google Scholar 

  22. Boyle PA, Buchman AS, Wilson RS, Leurgans SE, Bennett DA. Physical frailty is associated with incident mild cognitive impairment in community-based older persons. Journal of the American Geriatrics Society; 2010;58(2):248–55. doi: 10.1111/j.1532-5415.2009.02671.x.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Johnson DK, Wilkins CH, Morris JC. Accelerated weight loss may precede diagnosis in Alzheimer disease. Archives of neurology; 2006;63(9):1312–7. doi: 10.1001/archneur.63.9.1312.

    Article  PubMed  Google Scholar 

  24. Morris JC, Weintraub S, Chui HC, Cummings J, Decarli C, Ferris S, Foster NL, Galasko D, Graff-Radford N, Peskind ER, et al. The Uniform Data Set (UDS): clinical and cognitive variables and descriptive data from Alzheimer Disease Centers. Alzheimer disease and associated disorders; 2006;20(4):210–6. doi: 10.1097/01. wad.0000213865.09806.92.

    Article  PubMed  Google Scholar 

  25. Jefferson AL, Hohman TJ, Liu D, Haj-Hassan S, Gifford KA, Benson EM, Skinner JS, Lu Z, Sparling J, Sumner EC, et al. Adverse vascular risk is related to cognitive decline in older adults. Journal of Alzheimer’s disease: JAD; 2015;44(4):1361–73. doi: 10.3233/JAD-141812.

    PubMed  PubMed Central  Google Scholar 

  26. Wolf PA, D’Agostino RB, Belanger AJ, Kannel WB. Probability of stroke: a risk profile from the Framingham Study. Stroke; a journal of cerebral circulation; 1991;22(3):312–8.

    Article  CAS  Google Scholar 

  27. Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, Gamst A, Holtzman DM, Jagust WJ, Petersen RC, et al. The diagnosis of mild cognitive impairment due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimer’s & dementia: the journal of the Alzheimer’s Association; 2011;7(3):270–9. doi: 10.1016/j.jalz.2011.03.008.

    Article  Google Scholar 

  28. McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR, Jr., Kawas CH, Klunk WE, Koroshetz WJ, Manly JJ, Mayeux R, et al. The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimer’s & dementia: the journal of the Alzheimer’s Association; 2011;7(3):263–9. doi: 10.1016/j.jalz.2011.03.005.

    Article  Google Scholar 

  29. McKeith IG, Galasko D, Kosaka K, Perry EK, Dickson DW, Hansen LA, Salmon DP, Lowe J, Mirra SS, Byrne EJ, et al. Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop. Neurology; 1996;47(5):1113–24.

    Article  CAS  PubMed  Google Scholar 

  30. Roman GC, Tatemichi TK, Erkinjuntti T, Cummings JL, Masdeu JC, Garcia JH, Amaducci L, Orgogozo JM, Brun A, Hofman A, et al. Vascular dementia: diagnostic criteria for research studies. Report of the NINDS-AIREN International Workshop. Neurology; 1993;43(2):250–60.

    CAS  PubMed  Google Scholar 

  31. Neary D, Snowden JS, Gustafson L, Passant U, Stuss D, Black S, Freedman M, Kertesz A, Robert PH, Albert M, et al. (Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology; 1998;51(6):1546–54.

    Article  CAS  PubMed  Google Scholar 

  32. Litvan I, Agid Y, Calne D, Campbell G, Dubois B, Duvoisin RC, Goetz CG, Golbe LI, Grafman J, Growdon JH, et al. Clinical research criteria for the diagnosis of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome): report of the NINDS-SPSP international workshop. Neurology; 1996;47(1):1–9.

    Article  CAS  PubMed  Google Scholar 

  33. Litvan I, Bhatia KP, Burn DJ, Goetz CG, Lang AE, McKeith I, Quinn N, Sethi KD, Shults C, Wenning GK, et al. Movement Disorders Society Scientific Issues Committee report: SIC Task Force appraisal of clinical diagnostic criteria for Parkinsonian disorders. Movement disorders: official journal of the Movement Disorder Society; 2003;18(5):467–86. doi: 10.1002/mds.10459.

    Article  Google Scholar 

  34. Mesulam MM. Primary progressive aphasia. Annals of neurology; 2001;49(4):425–32.

    Article  CAS  PubMed  Google Scholar 

  35. Association AP. Diagnostic and statistical manual of mental disorders (DSM-IV). American Psychiatric Association., 1994

    Google Scholar 

  36. Abner EL, Kryscio RJ, Cooper GE, Fardo DW, Jicha GA, Mendiondo MS, Nelson PT, Smith CD, Van Eldik LJ, Wan L, et al. Mild cognitive impairment: statistical models of transition using longitudinal clinical data. Int J Alzheimers Dis; 2012:291920. doi: 10.1155/2012/291920.

    Google Scholar 

  37. Farrer LA, Cupples LA, Haines JL, Hyman B, Kukull WA, Mayeux R, Myers RH, Pericak-Vance MA, Risch N, van Duijn CM. Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium. JAMA; 1997;278(16):1349–56.

    Article  CAS  PubMed  Google Scholar 

  38. Rissanen A, Heliovaara M, Aromaa A. Overweight and anthropometric changes in adulthood: a prospective study of 17,000 Finns. International journal of obesity; 1998;12(5):391–401.

    Google Scholar 

  39. Stevens J, Cai J, Pamuk ER, Williamson DF, Thun MJ, Wood JL. The effect of age on the association between body-mass index and mortality. The New England journal of medicine; 1998;338(1):1–7. doi: 10.1056/NEJM199801013380101.

    Article  CAS  PubMed  Google Scholar 

  40. Manson JE, Willett WC, Stampfer MJ, Colditz GA, Hunter DJ, Hankinson SE, Hennekens CH, Speizer FE. Body weight and mortality among women. The New England journal of medicine; 1995;333(11):677–85. doi: 10.1056/NEJM199509143331101.

    Article  CAS  PubMed  Google Scholar 

  41. Calle EE, Thun MJ, Petrelli JM, Rodriguez C, Heath CW, Jr. Body-mass index and mortality in a prospective cohort of U.S. adults. The New England journal of medicine; 1999;341(15):1097–105. doi: 10.1056/NEJM199910073411501.

    Article  CAS  PubMed  Google Scholar 

  42. Cornoni-Huntley JC, Harris TB, Everett DF, Albanes D, Micozzi MS, Miles TP, Feldman JJ. An overview of body weight of older persons, including the impact on mortality. The National Health and Nutrition Examination Survey I—Epidemiologic Follow-up Study. Journal of clinical epidemiology; 1991;44(8):743–53.

    Article  CAS  PubMed  Google Scholar 

  43. Kivipelto M, Ngandu T, Fratiglioni L, Viitanen M, Kareholt I, Winblad B, Helkala EL, Tuomilehto J, Soininen H, Nissinen A. Obesity and vascular risk factors at midlife and the risk of dementia and Alzheimer disease. Archives of neurology; 2005;62(10):1556–60. doi: 10.1001/archneur.62.10.1556.

    Article  PubMed  Google Scholar 

  44. Burns JM, Johnson DK, Watts A, Swerdlow RH, Brooks WM. Reduced lean mass in early Alzheimer disease and its association with brain atrophy. Archives of neurology; 2010;67(4):428–33. doi: 10.1001/archneurol.2010.38.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Wilkins CH, Roe CM, Morris JC, Galvin JE. Mild physical impairment predicts future diagnosis of dementia of the Alzheimer’s type. Journal of the American Geriatrics Society; 2013;61(7):1055–9. doi: 10.1111/jgs.12255.

    Article  PubMed  Google Scholar 

  46. Hubbard RE, O’Mahony MS, Savva GM, Calver BL, Woodhouse KW. Inflammation and frailty measures in older people. Journal of cellular and molecular medicine; 2009;13(9B):3103–9. doi: 10.1111/j.1582-4934.2009.00733.x.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Marzetti E, Calvani R, Bernabei R, Leeuwenburgh C. Apoptosis in skeletal myocytes: a potential target for interventions against sarcopenia and physical frailty-a minireview. Gerontology; 2012;58(2):99–106. doi: 10.1159/000330064.

    Article  CAS  PubMed  Google Scholar 

  48. McGeer EG, McGeer PL. Neuroinflammation in Alzheimer’s disease and mild cognitive impairment: a field in its infancy. Journal of Alzheimer’s disease: JAD; 2010;19(1):355–61. doi: 10.3233/JAD-2010-1219.

    Article  PubMed  Google Scholar 

  49. Qiu C, Winblad B, Fratiglioni L. The age-dependent relation of blood pressure to cognitive function and dementia. Lancet Neurol; 2005;4(8):487–99. doi: 10.1016/S1474-4422(05)70141-1.

    Article  PubMed  Google Scholar 

  50. Ninomiya T, Ohara T, Hirakawa Y, Yoshida D, Doi Y, Hata J, Kanba S, Iwaki T, Kiyohara Y. Midlife and late-life blood pressure and dementia in Japanese elderly: the Hisayama study. Hypertension; 2011;58(1):22–8. doi: 10.1161/HYPERTENSIONAHA.110.163055.

    Article  CAS  PubMed  Google Scholar 

  51. Mielke MM, Zandi PP, Sjogren M, Gustafson D, Ostling S, Steen B, Skoog I. High total cholesterol levels in late life associated with a reduced risk of dementia. Neurology; 2005;64(10):1689–95. doi: 10.1212/01.WNL.0000161870.78572.A5.

    Article  CAS  PubMed  Google Scholar 

  52. Linn RT, Wolf PA, Bachman DL, Knoefel JE, Cobb JL, Belanger AJ, Kaplan EF, D’Agostino RB. The ‘preclinical phase’ of probable Alzheimer’s disease. A 13-year prospective study of the Framingham cohort. Archives of neurology; 1995;52(5):485–90.

    CAS  PubMed  Google Scholar 

  53. Musiek ES, Holtzman DM. Origins of Alzheimer’s disease: reconciling cerebrospinal fluid biomarker and neuropathology data regarding the temporal sequence of amyloid-beta and tau involvement. Current opinion in neurology; 2012;25(6):715–20. doi: 10.1097/WCO.0b013e32835a30f4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Gorelick PB, Scuteri A, Black SE, Decarli C, Greenberg SM, Iadecola C, Launer LJ, Laurent S, Lopez OL, Nyenhuis D, et al. Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the american heart association/american stroke association. Stroke; a journal of cerebral circulation; 2011;42(9):2672–713. doi: 10.1161/STR.0b013e3182299496.

    Article  PubMed Central  Google Scholar 

  55. Tang MX, Cross P, Andrews H, Jacobs DM, Small S, Bell K, Merchant C, Lantigua R, Costa R, Stern Y, et al. Incidence of AD in African-Americans, Caribbean Hispanics, and Caucasians in northern Manhattan. Neurology; 2001;56(1):49–56.

    Article  CAS  PubMed  Google Scholar 

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Bell, S.P., Liu, D., Samuels, L.R. et al. Late-life body mass index, rapid weight loss, apolipoprotein E ε4 and the risk of cognitive decline and incident dementia. J Nutr Health Aging 21, 1259–1267 (2017). https://doi.org/10.1007/s12603-017-0906-3

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