Generic placeholder image

Current Alzheimer Research

Editor-in-Chief

ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

Research Article

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

In Press, (this is not the final "Version of Record"). Available online 22 July, 2024
Author(s): Ming-Zhan Zhang, Yan Sun, Yan-Ming Chen, Fan Guo, Pei-Yang Gao, Lan Tan and Meng-Shan Tan*
Published on: 22 July, 2024

DOI: 10.2174/0115672050314397240708060314

Price: $95

Abstract

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.

[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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/10.3390/ijerph18041673] [PMID: 33572441]
[6]
Salisbury C. Multimorbidity: Redesigning health care for people who use it. Lancet 2012; 380(9836): 7-9.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/10.1002/alz.12237] [PMID: 33403740]
[16]
Wetterling T. Pathogenesis of multimorbidity—what is known? Z Gerontol Geriatr 2021; 54(6): 590-6.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/10.1016/j.pneurobio.2011.09.005] [PMID: 21930184]
[31]
Biomarker promise for Parkinson’s disease. Lancet Neurol 2010; 9(12): 1139.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/10.1001/jamaneurol.2014.65] [PMID: 24687146]
[53]
Larkin M. Polly Matzinger: Immunology’s dangerous thinker. Lancet 1997; 350(9070): 38.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/10.1126/sciadv.abq5423] [PMID: 36608133]
[63]
Middeldorp J, Hol EM. GFAP in health and disease. Prog Neurobiol 2011; 93(3): 421-43.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/10.1016/j.neuron.2019.10.010] [PMID: 31759806]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy