Neuropsychiatric Symptoms are Related to Blood-biomarkers in Major Neurocognitive Disorders

Page: [74 - 84] Pages: 11

  • * (Excluding Mailing and Handling)

Abstract

Background: Neuropsychiatric symptoms (NPS) are highly prevalent among individuals with major neurocognitive disorders (MNCD). Objective: Here, we characterized blood biomarkers (metabolic, inflammatory, neurotrophic profiles and total antioxidant), body composition, physical fitness and quality of life (QoL) in individuals with MNCD according to NPS.

Methods: The sample comprised 34 older adults (71.4% women; 74.06±6.03 yrs, with MNCD diagnosis) categorized according to 50th percentile [Low (≤12) or High (≥13)] for NPS (Neuropsychiatric Inventory Questionnaire). Sociodemographic, clinical data, body composition, anthropometric, cognitive assessment (ADAS-Cog), physical fitness (Senior Fitness Test), QoL (QoL-Alzheimer’s Disease scale) were evaluated, and blood samples were collected for biochemical analysis.

Results: Low compared to high NPS group showed higher levels of IL-6, IGF-1and neurotrophic zscore (composite of IGF-1, VEGF-1, BDNF). Additionally, low compared to high NPS group have higher QoL, aerobic fitness and upper body and lower body strength.

Conclusion: The severity of NPS seems to be related to modified neurotrophic and inflammatory outcomes, lower physical fitness, and poor QoL. Strategies to counteract NPS development may preserve the physical and mental health of individuals with MNCD.

Graphical Abstract

[1]
Livingston G, Huntley J, Sommerlad A, et al. Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. Lancet 2020; 396(10248): 413-46.
[http://dx.doi.org/10.1016/S0140-6736(20)30367-6] [PMID: 32738937]
[2]
Gerlach LB, Kales HC. Pharmacological management of neuropsychiatric symptoms of dementia. Curr Treat Options Psychiatry 2020; 7(4): 489-507.
[http://dx.doi.org/10.1007/s40501-020-00233-9] [PMID: 33344107]
[3]
Chapman KR, Tremont G, Malloy P, Spitznagel MB. The role of sexual disinhibition to predict caregiver burden and desire to institutionalize among family dementia caregivers. J Geriatr Psychiatry Neurol 2020; 33(1): 42-51.
[http://dx.doi.org/10.1177/0891988719856688] [PMID: 31203702]
[4]
Sampaio A, Marques-Aleixo I, Seabra A, Mota J, Carvalho J. Physical exercise for individuals with dementia: Potential benefits perceived by formal caregivers. BMC Geriatr 2021; 21(1): 6.
[http://dx.doi.org/10.1186/s12877-020-01938-5] [PMID: 33407194]
[5]
Ng KP, Pascoal TA, Mathotaarachchi S, et al. Neuropsychiatric symptoms are early indicators of an upcoming metabolic decline in Alzheimer’s disease. Transl Neurodegener 2021; 10(1): 1.
[http://dx.doi.org/10.1186/s40035-020-00225-y] [PMID: 33390174]
[6]
Okabe K, Nagata T, Shinagawa S, et al. Effects of neuropsychiatric symptoms of dementia on reductions in activities of daily living in patients with Alzheimer’s disease. Geriatr Gerontol Int 2020; 20(6): 584-8.
[http://dx.doi.org/10.1111/ggi.13918] [PMID: 32232948]
[7]
Saari T, Hallikainen I, Hintsa T, Koivisto AM. Neuropsychiatric symptoms and activities of daily living in Alzheimer’s disease: ALSOVA 5-year follow-up study. Int Psychogeriatr 2020; 32(6): 741-51.
[http://dx.doi.org/10.1017/S1041610219001571] [PMID: 31656211]
[8]
Camina Martín MA, de Mateo Silleras B, Redondo del Río MP. Body composition analysis in older adults with dementia. Anthropometry and bioelectrical impedance analysis: A critical review. Eur J Clin Nutr 2014; 68(11): 1228-33.
[http://dx.doi.org/10.1038/ejcn.2014.168] [PMID: 25117995]
[9]
Sampaio A, Marques-Aleixo I, Seabra A, Mota J, Marques E, Carvalho J. Physical fitness in institutionalized older adults with dementia: Association with cognition, functional capacity and quality of life. Aging Clin Exp Res 2020; 32(11): 2329-38.
[http://dx.doi.org/10.1007/s40520-019-01445-7] [PMID: 31927709]
[10]
Hall JR, Wiechmann AR, Johnson LA, et al. Biomarkers of vascular risk, systemic inflammation, and microvascular pathology and neuropsychiatric symptoms in Alzheimer’s disease. J Alzheimers Dis 2013; 35(2): 363-71.
[http://dx.doi.org/10.3233/JAD-122359] [PMID: 23403534]
[11]
Holmes C, Cunningham C, Zotova E, Culliford D, Perry VH. Proinflammatory cytokines, sickness behavior, and Alzheimer disease. Neurology 2011; 77(3): 212-8.
[http://dx.doi.org/10.1212/WNL.0b013e318225ae07] [PMID: 21753171]
[12]
Nagata T, Kobayashi N, Shinagawa S, Yamada H, Kondo K, Nakayama K. Plasma BDNF levels are correlated with aggressiveness in patients with amnestic mild cognitive impairment or Alzheimer disease. J Neural Transm (Vienna) 2014; 121(4): 433-41.
[http://dx.doi.org/10.1007/s00702-013-1121-y] [PMID: 24253237]
[13]
Cummings JL, Mega M, Gray K, Rosenberg-Thompson S, Carusi DA, Gornbein J. The Neuropsychiatric Inventory: Comprehensive assessment of psychopathology in dementia. Neurology 1994; 44(12): 2308-14.
[http://dx.doi.org/10.1212/WNL.44.12.2308] [PMID: 7991117]
[14]
Lyketsos CG, Lopez O, Jones B, Fitzpatrick AL, Breitner J, DeKosky S. Prevalence of neuropsychiatric symptoms in dementia and mild cognitive impairment: Results from the cardiovascular health study. JAMA 2002; 288(12): 1475-83.
[http://dx.doi.org/10.1001/jama.288.12.1475] [PMID: 12243634]
[15]
Peters ME, Rosenberg PB, Steinberg M, et al. Neuropsychiatric symptoms as risk factors for progression from CIND to dementia: The Cache County Study. Am J Geriatr Psychiatry 2013; 21(11): 1116-24.
[http://dx.doi.org/10.1016/j.jagp.2013.01.049] [PMID: 23567370]
[16]
Nogueira J, Freitas S, Duro D, Almeida J, Santana I. Validation study of the Alzheimer’s disease assessment scale–cognitive subscale (ADAS-Cog) for the Portuguese patients with mild cognitive impairment and Alzheimer’s disease. Clin Neuropsychol 2018; 32 (Suppl. 1): 46-59.
[http://dx.doi.org/10.1080/13854046.2018.1454511] [PMID: 29566598]
[17]
Rosen WG, Mohs RC, Davis KL. A new rating scale for Alzheimer’s disease. Am J Psychiatry 1984; 141(11): 1356-64.
[http://dx.doi.org/10.1176/ajp.141.11.1356] [PMID: 6496779]
[18]
Rikli RE, Jones CJ. Development and validation of a functional fitness test for community-residing older adults. J Aging Phys Act 1999; 7(2): 129-61.
[http://dx.doi.org/10.1123/japa.7.2.129]
[19]
Rikli RE, Jones CJ. Senior fitness test manual. Champaign: Human Kinetics 2001.
[20]
Hesseberg K, Bentzen H, Ranhoff AH, Engedal K, Bergland A. Physical fitness in older people with mild cognitive impairment and dementia. J Aging Phys Act 2016; 24(1): 92-100.
[http://dx.doi.org/10.1123/japa.2014-0202] [PMID: 26098078]
[21]
Pavasini R, Guralnik J, Brown JC, et al. Short Physical Performance Battery and all-cause mortality: Systematic review and meta-analysis. BMC Med 2016; 14(1): 215.
[http://dx.doi.org/10.1186/s12916-016-0763-7] [PMID: 28003033]
[22]
Guralnik JM, Simonsick EM, Ferrucci L, et al. A short physical performance battery assessing lower extremity function: Association with self-reported disability and prediction of mortality and nursing home admission. J Gerontol 1994; 49(2): M85-94.
[http://dx.doi.org/10.1093/geronj/49.2.M85] [PMID: 8126356]
[23]
Kwon S, Perera S, Pahor M, et al. What is a meaningful change in physical performance? Findings from a clinical trial in older adults (the LIFE-P study). J Nutr Health Aging 2009; 13(6): 538-44.
[http://dx.doi.org/10.1007/s12603-009-0104-z] [PMID: 19536422]
[24]
Mendes J, Amaral TF, Borges N, et al. Handgrip strength values of Portuguese older adults: A population based study. BMC Geriatr 2017; 17(1): 191-1.
[http://dx.doi.org/10.1186/s12877-017-0590-5] [PMID: 28835211]
[25]
Sousa-Santos AR, Amaral TF. Differences in handgrip strength protocols to identify sarcopenia and frailty - a systematic review. BMC Geriatr 2017; 17(1): 238.
[http://dx.doi.org/10.1186/s12877-017-0625-y] [PMID: 29037155]
[26]
Bárrios HSG. Adaptação cultural e linguística e validação do instrumento QOL-AD para Portugal. 2013. Available from: https://repositorio.ul.pt/handle/10451/8409
[27]
Miller M, Stone NJ, Ballantyne C, et al. Triglycerides and cardiovascular disease: A scientific statement from the American Heart Association. Circulation 2011; 123(20): 2292-333.
[http://dx.doi.org/10.1161/CIR.0b013e3182160726] [PMID: 21502576]
[28]
Patterson MB, Whitehouse PJ, Edland SD, et al. ADCS Prevention Instrument Project: Quality of life assessment (QOL). Alzheimer Dis Assoc Disord 2006; 20(4) (Suppl. 3): S179-90.
[http://dx.doi.org/10.1097/01.wad.0000213874.25053.e5] [PMID: 17135811]
[29]
Nepal B, Brown LJ, Anstey KJ. Rising midlife obesity will worsen future prevalence of dementia. PLoS One 2014; 9(9): e99305.
[http://dx.doi.org/10.1371/journal.pone.0099305] [PMID: 25184830]
[30]
Liberman K, Forti LN, Beyer I, Bautmans I. The effects of exercise on muscle strength, body composition, physical functioning and the inflammatory profile of older adults. Curr Opin Clin Nutr Metab Care 2017; 20(1): 30-53.
[http://dx.doi.org/10.1097/MCO.0000000000000335] [PMID: 27755209]
[31]
Venkatraman VK, Sanderson A, Cox KL, et al. Effect of a 24-month physical activity program on brain changes in older adults at risk of Alzheimer’s disease: The AIBL active trial. Neurobiol Aging 2020; 89: 132-41.
[http://dx.doi.org/10.1016/j.neurobiolaging.2019.02.030] [PMID: 31324405]
[32]
Westerterp KR. Exercise, energy balance and body composition. Eur J Clin Nutr 2018; 72(9): 1246-50.
[http://dx.doi.org/10.1038/s41430-018-0180-4] [PMID: 30185845]
[33]
Ferrucci L, Guralnik JM, Studenski S, Fried LP, Cutler GB Jr, Walston JD. Designing randomized, controlled trials aimed at preventing or delaying functional decline and disability in frail, older persons: A consensus report. J Am Geriatr Soc 2004; 52(4): 625-34.
[http://dx.doi.org/10.1111/j.1532-5415.2004.52174.x] [PMID: 15066083]
[34]
Conde-Sala JL, Reñé-Ramírez R, Turró-Garriga O, et al. Severity of dementia, anosognosia, and depression in relation to the quality of life of patients with Alzheimer disease: Discrepancies between patients and caregivers. Am J Geriatr Psychiatry 2014; 22(2): 138-47.
[http://dx.doi.org/10.1016/j.jagp.2012.07.001] [PMID: 23567444]
[35]
Sampaio A, Marques EA, Mota J, Carvalho J. Effects of a multicomponent exercise program in institutionalized elders with Alzheimer’s disease. Dementia 2019; 18(2): 417-31.
[http://dx.doi.org/10.1177/1471301216674558] [PMID: 27756836]
[36]
Mendonça DCB, Fernandes DR, Hernandez SS, Soares FDG, Figueiredo K, Coelho FGM. Physical exercise is effective for neuropsychiatric symptoms in Alzheimer’s disease: A systematic review. Arq Neuropsiquiatr 2021; 79(5): 447-56.
[http://dx.doi.org/10.1590/0004-282x-anp-2020-0284] [PMID: 34161531]
[37]
Kouloutbani K, Venetsanou F, Markati A, Karteroliotis KE, Politis A. The effectiveness of physical exercise interventions in the management of neuropsychiatric symptoms in dementia patients: A systematic review. Int Psychogeriatr 2021; 34(2): 177-90.
[PMID: 33818342]
[38]
Vreugdenhil A, Cannell J, Davies A, Razay G. A community-based exercise programme to improve functional ability in people with Alzheimer’s disease: A randomized controlled trial. Scand J Caring Sci 2012; 26(1): 12-9.
[http://dx.doi.org/10.1111/j.1471-6712.2011.00895.x] [PMID: 21564154]
[39]
Lam FMH, Huang MZ, Liao LR, Chung RCK, Kwok TCY, Pang MYC. Physical exercise improves strength, balance, mobility, and endurance in people with cognitive impairment and dementia: A systematic review. J Physiother 2018; 64(1): 4-15.
[http://dx.doi.org/10.1016/j.jphys.2017.12.001] [PMID: 29289581]
[40]
Sobol NA, Dall CH, Høgh P, et al. Change in fitness and the relation to change in cognition and neuropsychiatric symptoms after aerobic exercise in patients with mild Alzheimer’s disease. J Alzheimers Dis 2018; 65(1): 137-45.
[http://dx.doi.org/10.3233/JAD-180253] [PMID: 30040719]
[41]
Morris JK, Vidoni ED, Johnson DK, et al. Aerobic exercise for Alzheimer’s disease: A randomized controlled pilot trial. PLoS One 2017; 12(2): e0170547.
[http://dx.doi.org/10.1371/journal.pone.0170547] [PMID: 28187125]
[42]
Qu Y, Ma YH, Huang YY, et al. Blood biomarkers for the diagnosis of amnestic mild cognitive impairment and Alzheimer’s disease: A systematic review and meta-analysis. Neurosci Biobehav Rev 2021; 128: 479-86.
[http://dx.doi.org/10.1016/j.neubiorev.2021.07.007] [PMID: 34245759]
[43]
Nowrangi MA. Neuropsychiatric aspects of alzheimer dementia. Psychiatr Clin North Am 2020; 43(2): 383-97.
[http://dx.doi.org/10.1016/j.psc.2020.02.012] [PMID: 32439028]
[44]
Cunningham C, Campion S, Lunnon K, et al. Systemic inflammation induces acute behavioral and cognitive changes and accelerates neurodegenerative disease. Biol Psychiatry 2009; 65(4): 304-12.
[http://dx.doi.org/10.1016/j.biopsych.2008.07.024] [PMID: 18801476]
[45]
Takeda S, Sato N, Morishita R. Systemic inflammation, blood-brain barrier vulnerability and cognitive/non-cognitive symptoms in Alzheimer disease: Relevance to pathogenesis and therapy. Front Aging Neurosci 2014; 6: 171.
[http://dx.doi.org/10.3389/fnagi.2014.00171] [PMID: 25120476]
[46]
Pearson TA, Mensah GA, Alexander RW, et al. Markers of inflammation and cardiovascular disease: Application to clinical and public health practice: A statement for healthcare professionals from the centers for disease control and prevention and the american heart association. Circulation 2003; 107(3): 499-511.
[http://dx.doi.org/10.1161/01.CIR.0000052939.59093.45] [PMID: 12551878]
[47]
James H. Biomarkers and depressive symptoms in a sample of cognitively intact and Alzheimer’s disease elderly males. Neurosci Med 2011; 2(4): 306-12.
[48]
Vorobyov V, Bobkova N. The brain compensatory mechanisms and Alzheimer-s disease progression: A new protective strategy. Neural Regen Res 2015; 10(5): 696-7.
[http://dx.doi.org/10.4103/1673-5374.156954] [PMID: 26109935]
[49]
Holmgren S, Hjorth E, Schultzberg M, et al. Neuropsychiatric symptoms in dementia—A role for neuroinflammation? Brain Res Bull 2014; 108: 88-93.
[http://dx.doi.org/10.1016/j.brainresbull.2014.09.003] [PMID: 25224917]
[50]
Pedersen BK, Steensberg A, Fischer C, Keller C, Ostrowski K, Schjerling P. Exercise and cytokines with particular focus on muscle-derived IL-6. Exerc Immunol Rev 2001; 7: 18-31.
[PMID: 11579746]
[51]
Xu LZ, Li FY, Li BQ, et al. Decreased levels of insulin-like growth factor-1 are associated with alzheimer’s disease: A meta-analysis. J Alzheimers Dis 2021; 82(3): 1357-67.
[http://dx.doi.org/10.3233/JAD-210516] [PMID: 34151815]
[52]
Swerdlow RH, Burns JM, Khan SM. The Alzheimer’s disease mitochondrial cascade hypothesis: Progress and perspectives. Biochim Biophys Acta Mol Basis Dis 2014; 1842(8): 1219-31.
[http://dx.doi.org/10.1016/j.bbadis.2013.09.010] [PMID: 24071439]
[53]
Loeffler DA. Modifiable, non-modifiable, and clinical factors associated with progression of Alzheimer’s disease. J Alzheimers Dis 2021; 80(1): 1-27.
[http://dx.doi.org/10.3233/JAD-201182] [PMID: 33459643]
[54]
Büttiker P, Weissenberger S, Esch T, et al. Dysfunctional mitochondrial processes contribute to energy perturbations in the brain and neuropsychiatric symptoms. Front Pharmacol 2023; 13: 1095923.
[http://dx.doi.org/10.3389/fphar.2022.1095923] [PMID: 36686690]
[55]
Marques-Aleixo I, Beleza J, Sampaio A, et al. Preventive and therapeutic potential of physical exercise in neurodegenerative diseases. Antioxid Redox Signal 2021; 34(8): 674-93.
[http://dx.doi.org/10.1089/ars.2020.8075] [PMID: 32159378]