Associations of Multimorbidity with Cerebrospinal Fluid Biomarkers for Neurodegenerative Disorders in Early Parkinson's Disease: A Crosssectional and Longitudinal Study


如何引用文章

全文:

详细

Object:The study aims to determine whether multimorbidity status is associated with cerebrospinal fluid (CSF) biomarkers for neurodegenerative disorders.

Methods:A total of 827 patients were enrolled from the Parkinson’s Progression Markers Initiative (PPMI) database, including 638 patients with early-stage Parkinson’s disease (PD) and 189 healthy controls (HCs). Multimorbidity status was evaluated based on the count of long-term conditions (LTCs) and the multimorbidity pattern. Using linear regression models, cross-sectional and longitudinal analyses were conducted to assess the associations of multimorbidity status with CSF biomarkers for neurodegenerative disorders, including α-synuclein (αSyn), amyloid-β42 (Aβ42), total tau (t-tau), phosphorylated tau (p-tau), glial fibrillary acidic protein (GFAP), and neurofilament light chain protein (NfL).

Results:At baseline, the CSF t-tau (p = 0.010), p-tau (p = 0.034), and NfL (p = 0.049) levels showed significant differences across the three categories of LTC counts. In the longitudinal analysis, the presence of LTCs was associated with lower Aβ42 (β < -0.001, p = 0.020), and higher t-tau (β = 0.007, p = 0.026), GFAP (β = 0.013, p = 0.022) and NfL (β = 0.020, p = 0.012); Participants with tumor/musculoskeletal/mental disorders showed higher CSF levels of t-tau (β = 0.016, p = 0.011) and p-tau (β = 0.032, p = 0.044) than those without multimorbidity.

Conclusion:Multimorbidity, especially severe multimorbidity and the pattern of mental/musculoskeletal/ tumor disorders, was associated with CSF biomarkers for neurodegenerative disorders in early-stage PD patients, suggesting that multimorbidity might play a crucial role in aggravating neuronal damage in neurodegenerative diseases.

作者简介

Ming-Zhan Zhang

School of Clinical Medicine, Shandong Second Medical University (formerly Weifang Medical University)

Email: info@benthamscience.net

Yan Sun

Department of Neurology, Qingdao Municipal Hospital, Qingdao University

Email: info@benthamscience.net

Yan-Ming Chen

Department of Neurology, Qingdao Municipal Hospital, Qingdao University

Email: info@benthamscience.net

Fan Guo

Department of Neurology, Qingdao Municipal Hospital, Qingdao University

Email: info@benthamscience.net

Pei-Yang Gao

Department of Neurology, Qingdao Municipal Hospital, Qingdao University

Email: info@benthamscience.net

Lan Tan

Department of Neurology, Qingdao Municipal Hospital, University of Health and Rehabilitation Sciences

Email: info@benthamscience.net

Meng-Shan Tan

School of Clinical Medicine, Shandong Second Medical University (formerly Weifang Medical University)

编辑信件的主要联系方式.
Email: info@benthamscience.net

参考

  1. Multimorbidity. Geneva: World Health Organization 2016.
  2. Johnston MC, Crilly M, Black C, Prescott GJ, Mercer SW. Defining and measuring multimorbidity: A systematic review of systematic reviews. Eur J Public Health 2019; 29(1): 182-9. doi: 10.1093/eurpub/cky098 PMID: 29878097
  3. Barnett K, Mercer SW, Norbury M, Watt G, Wyke S, Guthrie B. Epidemiology of multimorbidity and implications for health care, research, and medical education: A cross-sectional study. Lancet 2012; 380(9836): 37-43. doi: 10.1016/S0140-6736(12)60240-2 PMID: 22579043
  4. Skou ST, Mair FS, Fortin M, et al. Multimorbidity. Nat Rev Dis Primers 2022; 8(1): 48. doi: 10.1038/s41572-022-00376-4 PMID: 35835758
  5. Chua YP, Xie Y, Lee PSS, Lee ES. Definitions and prevalence of multimorbidity in large database studies: A scoping review. Int J Environ Res Public Health 2021; 18(4): 1673. doi: 10.3390/ijerph18041673 PMID: 33572441
  6. Salisbury C. Multimorbidity: Redesigning health care for people who use it. Lancet 2012; 380(9836): 7-9. doi: 10.1016/S0140-6736(12)60482-6 PMID: 22579042
  7. Chudasama YV, Khunti K, Gillies CL, et al. Healthy lifestyle and life expectancy in people with multimorbidity in the UK Biobank: A longitudinal cohort study. PLoS Med 2020; 17(9): e1003332. doi: 10.1371/journal.pmed.1003332 PMID: 32960883
  8. Loza E, Jover JA, Rodriguez L, Carmona L. Multimorbidity: Prevalence, effect on quality of life and daily functioning, and variation of this effect when one condition is a rheumatic disease. Semin Arthritis Rheum 2009; 38(4): 312-9. doi: 10.1016/j.semarthrit.2008.01.004 PMID: 18336872
  9. Kanesarajah J, Waller M, Whitty JA, Mishra GD. Multimorbidity and quality of life at mid-life: A systematic review of general population studies. Maturitas 2018; 109: 53-62. doi: 10.1016/j.maturitas.2017.12.004 PMID: 29452782
  10. Rizzuto D, Orsini N, Qiu C, Wang H-X, Fratiglioni L. Lifestyle, social factors, and survival after age 75: Population based study. BMJ 2012; 345(2): e5568.
  11. Rai SN, Singh P, Steinbusch HWM, Vamanu E, Ashraf G, Singh MP. The role of vitamins in neurodegenerative disease: An update. Biomedicines 2021; 9(10): 1284. doi: 10.3390/biomedicines9101284 PMID: 34680401
  12. Masnoon N, Shakib S, Kalisch-Ellett L, Caughey GE. What is polypharmacy? A systematic review of definitions. BMC Geriatr 2017; 17(1): 230. doi: 10.1186/s12877-017-0621-2 PMID: 29017448
  13. Makovski TT, Schmitz S, Zeegers MP, Stranges S, van den Akker M. Multimorbidity and quality of life: Systematic literature review and meta-analysis. Ageing Res Rev 2019; 53: 100903. doi: 10.1016/j.arr.2019.04.005 PMID: 31048032
  14. Hu Y, Wang Z, He H, Pan L, Tu J, Shan G. Prevalence and patterns of multimorbidity in China during 2002–2022: A systematic review and meta-analysis. Ageing Res Rev 2024; 93: 102165. doi: 10.1016/j.arr.2023.102165 PMID: 38096988
  15. Grande G, Marengoni A, Vetrano DL, et al. Multimorbidity burden and dementia risk in older adults: The role of inflammation and genetics. Alzheimers Dement 2021; 17(5): 768-76. doi: 10.1002/alz.12237 PMID: 33403740
  16. Wetterling T. Pathogenesis of multimorbidity—what is known? Z Gerontol Geriatr 2021; 54(6): 590-6. doi: 10.1007/s00391-020-01752-z PMID: 32651847
  17. Barnes PJ. Mechanisms of development of multimorbidity in the elderly. Eur Respir J 2015; 45(3): 790-806. doi: 10.1183/09031936.00229714 PMID: 25614163
  18. Hely MA, Reid WGJ, Adena MA, Halliday GM, Morris JGL. The Sydney multicenter study of Parkinson’s disease: The inevitability of dementia at 20 years. Mov Disord 2008; 23(6): 837-44. doi: 10.1002/mds.21956 PMID: 18307261
  19. Ramakrishna K, Nalla LV, Naresh D, et al. WNT-β catenin signaling as a potential therapeutic target for neurodegenerative diseases: Current status and future perspective. Diseases 2023; 11(3): 89. doi: 10.3390/diseases11030089 PMID: 37489441
  20. Vassilaki M, Aakre JA, Mielke MM, et al. Multimorbidity and neuroimaging biomarkers among cognitively normal persons. Neurology 2016; 86(22): 2077-84. doi: 10.1212/WNL.0000000000002624 PMID: 27164657
  21. Mendes A, Tezenas du Montcel S, Levy M, et al. Multimorbidity is associated with preclinical alzheimer’s disease neuroimaging biomarkers. Dement Geriatr Cogn Disord 2018; 45(5-6): 272-81. doi: 10.1159/000489007 PMID: 29953971
  22. Vassilaki M, Aakre JA, Kremers WK, et al. The association of multimorbidity with preclinical AD stages and SNAP in cognitively unimpaired persons. J Gerontol A Biol Sci Med Sci 2019; 74(6): 877-83. doi: 10.1093/gerona/gly149 PMID: 30124772
  23. Aerqin Q, Chen XT, Ou YN, et al. Associations between multimorbidity burden and Alzheimer’s pathology in older adults without dementia: The CABLE study. Neurobiol Aging 2024; 134: 1-8. doi: 10.1016/j.neurobiolaging.2023.09.014 PMID: 37950963
  24. Parnetti L, Gaetani L, Eusebi P, et al. CSF and blood biomarkers for Parkinson’s disease. Lancet Neurol 2019; 18(6): 573-86. doi: 10.1016/S1474-4422(19)30024-9 PMID: 30981640
  25. Van Maurik IS, Vos SJ, Bos I, et al. Biomarker-based prognosis for people with mild cognitive impairment (ABIDE): A modelling study. Lancet Neurol 2019; 18(11): 1034-44. doi: 10.1016/S1474-4422(19)30283-2 PMID: 31526625
  26. Cousins KAQ, Irwin DJ, Tropea TF, Rhodes E, Phillips JS, Chen-Plotkin AS. Parkinson's progression markers initiative. Evaluation of ATN PD framework and biofluid markers to predict cognitive decline in early parkinson disease. Neurology 2023; 102(4): e208033.
  27. Milà-Alomà M, Salvadó G, Gispert JD, et al. Amyloid beta, tau, synaptic, neurodegeneration, and glial biomarkers in the preclinical stage of the Alzheimer’s continuum. Alzheimers Dement 2020; 16(10): 1358-71. doi: 10.1002/alz.12131 PMID: 32573951
  28. Lleó A, Cavedo E, Parnetti L, et al. Cerebrospinal fluid biomarkers in trials for Alzheimer and Parkinson diseases. Nat Rev Neurol 2015; 11(1): 41-55. doi: 10.1038/nrneurol.2014.232 PMID: 25511894
  29. Marek K, Chowdhury S, Siderowf A, et al. The Parkinson’s progression markers initiative (PPMI) – establishing a PD biomarker cohort. Ann Clin Transl Neurol 2018; 5(12): 1460-77. doi: 10.1002/acn3.644 PMID: 30564614
  30. Marek K, Jennings D, Lasch S, et al. The parkinson progression marker initiative (PPMI). Prog Neurobiol 2011; 95(4): 629-35. doi: 10.1016/j.pneurobio.2011.09.005 PMID: 21930184
  31. Biomarker promise for Parkinson’s disease. Lancet Neurol 2010; 9(12): 1139. doi: 10.1016/S1474-4422(10)70284-2 PMID: 21087732
  32. Monestime JP, Mayer RW, Blackwood A. Analyzing the ICD-10-CM transition and post-implementation stages: A public health institution case study. Perspect Health Inf Manag 2019; 16: 1a.
  33. Topaz M, Shafran-Topaz L, Bowles KH. ICD-9 to ICD-10: Evolution. Revolution, and Current Debates in the United States 2013.
  34. Jackson H, Anzures-Cabrera J, Taylor KI, Pagano G. Hoehn and yahr stage and striatal dat-spect uptake are predictors of parkinson’s disease motor progression. Front Neurosci 2021; 15: 765765. doi: 10.3389/fnins.2021.765765 PMID: 34966256
  35. Brumm MC, Siderowf A, Simuni T, et al. Parkinson’s progression markers initiative: A milestone-based strategy to monitor parkinson’s disease progression. J Parkinsons Dis 2023; 13(6): 899-916. doi: 10.3233/JPD-223433 PMID: 37458046
  36. Calderón-Larrañaga A, Vetrano DL, Onder G, et al. Assessing and measuring chronic nMultimorbidity in the older population: A proposal for its operationalization. J Gerontol A Biol Sci Med Sci 2016; glw233. doi: 10.1093/gerona/glw233 PMID: 28003375
  37. Guisado-Clavero M, Roso-Llorach A, López-Jimenez T, et al. Multimorbidity patterns in the elderly: A prospective cohort study with cluster analysis. BMC Geriatr 2018; 18(1): 16. doi: 10.1186/s12877-018-0705-7 PMID: 29338690
  38. Kang JH, Mollenhauer B, Coffey CS, et al. CSF biomarkers associated with disease heterogeneity in early Parkinson’s disease: The Parkinson’s Progression Markers Initiative study. Acta Neuropathol 2016; 131(6): 935-49. doi: 10.1007/s00401-016-1552-2 PMID: 27021906
  39. Bartl M, Dakna M, Galasko D, et al. Biomarkers of neurodegeneration and glial activation validated in Alzheimer’s disease assessed in longitudinal cerebrospinal fluid samples of Parkinson’s disease. PLoS One 2021; 16(10): e0257372. doi: 10.1371/journal.pone.0257372 PMID: 34618817
  40. Sheng ZH, Ma LZ, Liu JY, et al. Cerebrospinal fluid neurofilament dynamic profiles predict cognitive progression in individuals with de novo Parkinson’s disease. Front Aging Neurosci 2022; 14: 1061096. doi: 10.3389/fnagi.2022.1061096 PMID: 36589544
  41. Ronaldson A, Arias de la Torre J, Ashworth M, et al. Associations between air pollution and multimorbidity in the UK Biobank: A cross-sectional study. Front Public Health 2022; 10: 1035415. doi: 10.3389/fpubh.2022.1035415 PMID: 36530697
  42. Ben Hassen C, Fayosse A, Landré B, et al. Association between age at onset of multimorbidity and incidence of dementia: 30 year follow-up in Whitehall II prospective cohort study. BMJ 2022; 376: e068005. doi: 10.1136/bmj-2021-068005 PMID: 35110302
  43. Hanlon P, Jani B, Mair F, McAllister D. Multimorbidity and frailty in middle-aged adults with type 2 diabetes mellitus.Diabetes and endocrine disease. American Academy of Family Physicians 2022; p. 2910. doi: 10.1370/afm.20.s1.2910
  44. Nie F, Xue J, Wu D, Wang R, Li H, Li X. Coordinate descent method for k-means. IEEE Trans Pattern Anal Mach Intell 2021; 1-1. doi: 10.1109/TPAMI.2021.3085739 PMID: 34061737
  45. Chen YT, Witten DM. Selective inference for k-means clustering. arXiv 2024.
  46. Liu B, Zhang T, Li Y, Liu Z, Zhang Z. Kernel probabilistic k-means clustering. Sensors 2021; 21(5): 1892. doi: 10.3390/s21051892 PMID: 33800353
  47. Wang Q, Zhang S, Wang Y, Zhao D, Chen X, Zhou C. The effect of dual sensory impairment and multimorbidity patterns on functional impairment: A longitudinal cohort of middle-aged and older adults in China. Front Aging Neurosci 2022; 14: 807383. doi: 10.3389/fnagi.2022.807383 PMID: 35462686
  48. Mattson MP, Chan SL, Duan W. Modification of brain aging and neurodegenerative disorders by genes, diet, and behavior. Physiol Rev 2002; 82(3): 637-72. doi: 10.1152/physrev.00004.2002 PMID: 12087131
  49. Petzinger GM, Fisher BE, McEwen S, Beeler JA, Walsh JP, Jakowec MW. Exercise-enhanced neuroplasticity targeting motor and cognitive circuitry in Parkinson’s disease. Lancet Neurol 2013; 12(7): 716-26. doi: 10.1016/S1474-4422(13)70123-6 PMID: 23769598
  50. Musiek ES, Holtzman DM. Mechanisms linking circadian clocks, sleep, and neurodegeneration. Science 2016; 354(6315): 1004-8. doi: 10.1126/science.aah4968 PMID: 27885006
  51. Zuccato C, Cattaneo E. Brain-derived neurotrophic factor in neurodegenerative diseases. Nat Rev Neurol 2009; 5(6): 311-22. doi: 10.1038/nrneurol.2009.54 PMID: 19498435
  52. Breen DP, Vuono R, Nawarathna U, et al. Sleep and circadian rhythm regulation in early Parkinson disease. JAMA Neurol 2014; 71(5): 589-95. doi: 10.1001/jamaneurol.2014.65 PMID: 24687146
  53. Larkin M. Polly Matzinger: Immunology’s dangerous thinker. Lancet 1997; 350(9070): 38. doi: 10.1016/S0140-6736(05)66254-X PMID: 9229665
  54. Sung YJ, Yang C, Norton J, et al. Proteomics of brain, CSF, and plasma identifies molecular signatures for distinguishing sporadic and genetic Alzheimer’s disease. Sci Transl Med 2023; 15(703): eabq5923. doi: 10.1126/scitranslmed.abq5923 PMID: 37406134
  55. Hafizi S, Rajji TK. Modifiable risk factors of dementia linked to excitation-inhibition imbalance. Ageing Res Rev 2023; 83: 101804. doi: 10.1016/j.arr.2022.101804 PMID: 36410620
  56. Morris A. Peripheral Aβ linked to pathogenesis of T2DM. Nat Rev Endocrinol 2017; 13(10): 564-4. doi: 10.1038/nrendo.2017.118 PMID: 28862268
  57. Ballatore C, Lee VMY, Trojanowski JQ. Tau-mediated neurodegeneration in Alzheimer’s disease and related disorders. Nat Rev Neurosci 2007; 8(9): 663-72. doi: 10.1038/nrn2194 PMID: 17684513
  58. Tracy TE, Madero-Pérez J, Swaney DL, et al. Tau interactome maps synaptic and mitochondrial processes associated with neurodegeneration. Cell 2022; 185(4): 712-728.e14. doi: 10.1016/j.cell.2021.12.041 PMID: 35063084
  59. Dolatshahi M, Pourmirbabaei S, Kamalian A, Ashraf-Ganjouei A, Yaseri M, Aarabi MH. Longitudinal alterations of alpha-synuclein, amyloid beta, total, and phosphorylated tau in cerebrospinal fluid and correlations between their changes in parkinson’s disease. Front Neurol 2018; 9: 560. doi: 10.3389/fneur.2018.00560 PMID: 30050494
  60. Visser D, Wolters EE, Verfaillie SCJ, et al. Tau pathology and relative cerebral blood flow are independently associated with cognition in Alzheimer’s disease. Eur J Nucl Med Mol Imaging 2020; 47(13): 3165-75. doi: 10.1007/s00259-020-04831-w PMID: 32462397
  61. Wang Y, Mandelkow E. Tau in physiology and pathology. Nat Rev Neurosci 2016; 17(1): 22-35. doi: 10.1038/nrn.2015.1 PMID: 26631930
  62. Ochoa E, Ramirez P, Gonzalez E, et al. Pathogenic tau–induced transposable element–derived dsRNA drives neuroinflammation. Sci Adv 2023; 9(1): eabq5423. doi: 10.1126/sciadv.abq5423 PMID: 36608133
  63. Middeldorp J, Hol EM. GFAP in health and disease. Prog Neurobiol 2011; 93(3): 421-43. doi: 10.1016/j.pneurobio.2011.01.005 PMID: 21219963
  64. Yang Z, Wang KKW. Glial fibrillary acidic protein: from intermediate filament assembly and gliosis to neurobiomarker. Trends Neurosci 2015; 38(6): 364-74. doi: 10.1016/j.tins.2015.04.003 PMID: 25975510
  65. Katsipis G, Tzekaki EE, Tsolaki M, Pantazaki AA. Salivary GFAP as a potential biomarker for diagnosis of mild cognitive impairment and Alzheimer’s disease and its correlation with neuroinflammation and apoptosis. J Neuroimmunol 2021; 361: 577744. doi: 10.1016/j.jneuroim.2021.577744 PMID: 34655990
  66. Tansey MG, Wallings RL, Houser MC, Herrick MK, Keating CE, Joers V. Inflammation and immune dysfunction in Parkinson disease. Nat Rev Immunol 2022; 22(11): 657-73. doi: 10.1038/s41577-022-00684-6 PMID: 35246670
  67. Blöndal V, Malinovschi A, Sundbom F, et al. Multimorbidity in asthma, association with allergy, inflammatory markers and symptom burden, results from the Swedish GA 2 LEN study. Clin Exp Allergy 2021; 51(2): 262-72. doi: 10.1111/cea.13759 PMID: 33053244
  68. Ferrucci L, Fabbri E. Inflammageing: Chronic inflammation in ageing, cardiovascular disease, and frailty. Nat Rev Cardiol 2018; 15(9): 505-22. doi: 10.1038/s41569-018-0064-2 PMID: 30065258
  69. Khalil M, Teunissen CE, Otto M, et al. Neurofilaments as biomarkers in neurological disorders. Nat Rev Neurol 2018; 14(10): 577-89. doi: 10.1038/s41582-018-0058-z PMID: 30171200
  70. Peltz CB, Kenney K, Gill J, Diaz-Arrastia R, Gardner RC, Yaffe K. Blood biomarkers of traumatic brain injury and cognitive impairment in older veterans. Neurology 2020; 95(9): e1126-33. doi: 10.1212/WNL.0000000000010087 PMID: 32571850
  71. Uyar M, Lezius S, Buhmann C, et al. Diabetes, Glycated Hemoglobin (HbA1c), and Neuroaxonal Damage in Parkinson’s Disease (MARK-PD Study). Mov Disord 2022; 37(6): 1299-304. doi: 10.1002/mds.29009 PMID: 35384057
  72. Aamodt WW, Waligorska T, Shen J, et al. Neurofilament light chain as a biomarker for cognitive decline in parkinson disease. Mov Disord 2021; 36(12): 2945-50. doi: 10.1002/mds.28779 PMID: 34480363
  73. Disanto G, Barro C, Benkert P, et al. Serum Neurofilament light: A biomarker of neuronal damage in multiple sclerosis. Ann Neurol 2017; 81(6): 857-70. doi: 10.1002/ana.24954 PMID: 28512753
  74. Olsson B, Portelius E, Cullen NC, et al. Association of cerebrospinal fluid neurofilament light protein levels with cognition in patients with dementia, motor neuron disease, and movement disorders. JAMA Neurol 2019; 76(3): 318-25. doi: 10.1001/jamaneurol.2018.3746 PMID: 30508027
  75. Mollenhauer B, Caspell-Garcia CJ, Coffey CS, et al. Longitudinal CSF biomarkers in patients with early Parkinson disease and healthy controls. Neurology 2017; 89(19): 1959-69. doi: 10.1212/WNL.0000000000004609 PMID: 29030452
  76. Abbasi N, Mohajer B, Abbasi S, Hasanabadi P, Abdolalizadeh A, Rajimehr R. Relationship between cerebrospinal fluid biomarkers and structural brain network properties in Parkinson’s disease. Mov Disord 2018; 33(3): 431-9. doi: 10.1002/mds.27284 PMID: 29436735
  77. Lei P, Ayton S, Finkelstein DI, Adlard PA, Masters CL, Bush AI. Tau protein: Relevance to parkinson’s disease. Int J Biochem Cell Biol 2010; 42(11): 1775-8. doi: 10.1016/j.biocel.2010.07.016 PMID: 20678581
  78. Shim KH, Kang MJ, Youn YC, An SSA, Kim S. Alpha-synuclein: A pathological factor with Aβ and tau and biomarker in Alzheimer’s disease. Alzheimers Res Ther 2022; 14(1): 201. doi: 10.1186/s13195-022-01150-0 PMID: 36587215
  79. Pech U, Verstreken P. α-Synuclein and Tau: Mitochondrial kill switches. Neuron 2018; 97(1): 3-4. doi: 10.1016/j.neuron.2017.12.024 PMID: 29301103
  80. McAleese KE, Colloby SJ, Thomas AJ, et al. Concomitant neurodegenerative pathologies contribute to the transition from mild cognitive impairment to dementia. Alzheimers Dement 2021; 17(7): 1121-33. doi: 10.1002/alz.12291 PMID: 33663011
  81. Violán C, Roso-Llorach A, Foguet-Boreu Q, et al. Multimorbidity patterns with K-means nonhierarchical cluster analysis. BMC Fam Pract 2018; 19(1): 108. doi: 10.1186/s12875-018-0790-x PMID: 29969997
  82. Kyrkanides S, Tallents RH, Miller JH, et al. Osteoarthritis accelerates and exacerbates Alzheimer’s disease pathology in mice. J Neuroinflammation 2011; 8(1): 112. doi: 10.1186/1742-2094-8-112 PMID: 21899735
  83. Ramakers IHGB, Verhey FRJ, Scheltens P, et al. Anxiety is related to Alzheimer cerebrospinal fluid markers in subjects with mild cognitive impairment. Psychol Med 2013; 43(5): 911-20. doi: 10.1017/S0033291712001870 PMID: 22954311
  84. Babulal GM, Ghoshal N, Head D, et al. Mood changes in cognitively normal older adults are linked to alzheimer disease biomarker levels. Am J Geriatr Psychiatry 2016; 24(11): 1095-104. doi: 10.1016/j.jagp.2016.04.004 PMID: 27426238
  85. Lebedeva A, Westman E, Lebedev AV, et al. Structural brain changes associated with depressive symptoms in the elderly with Alzheimer’s disease. J Neurol Neurosurg Psychiatry 2014; 85(8): 930-5. doi: 10.1136/jnnp-2013-307110 PMID: 24421287
  86. Gonzales MM, Insel PS, Nelson C, et al. Chronic depressive symptomatology and CSF amyloid beta and tau levels in mild cognitive impairment. Int J Geriatr Psychiatry 2018; 33(10): 1305-11. doi: 10.1002/gps.4926 PMID: 29953668
  87. Fabbri E, An Y, Zoli M, et al. Association between accelerated multimorbidity and age-related cognitive decline in older baltimore longitudinal study of aging participants without dementia. J Am Geriatr Soc 2016; 64(5): 965-72. doi: 10.1111/jgs.14092 PMID: 27131225
  88. Wei MY, Levine DA, Zahodne LB, Kabeto MU, Langa KM. Multimorbidity and cognitive decline over 14 years in older americans. J Gerontol A Biol Sci Med Sci 2020; 75(6): 1206-13. doi: 10.1093/gerona/glz147 PMID: 31173065
  89. Bassil F, Brown HJ, Pattabhiraman S, et al. Amyloid-Beta (Aβ) plaques promote seeding and spreading of alpha-synuclein and tau in a mouse model of lewy body disorders with aβ pathology. Neuron 2020; 105(2): 260-275.e6. doi: 10.1016/j.neuron.2019.10.010 PMID: 31759806

补充文件

附件文件
动作
1. JATS XML
下载

版权所有 © Bentham Science Publishers, 2024