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AIMS Neuroscience

2018, Volume 5, Issue 2: 148-161. doi: 10.3934/Neuroscience.2018.2.148
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Research article

Vascular biomarkers and ApoE4 expression in mild cognitive impairment and Alzheimer’s disease

  • 1.
    Universidad Católica Santa María La Antigua (USMA), Panamá
  • 2.
    Facultad de Medicina, Universidad de Panamá, Panamá
  • 3.
    Centro de Neurociencias y Unidad de Investigación Clínica, Instituto de Investigaciones Científicas y Servicios de Alta Tecnología (INDICASAT AIP), Panamá
  • 4.
    Servicio de Radiología, Complejo Hospitalario Arnulfo Arias Madrid, Caja del Seguro Social, Panamá
  • 5.
    Departmento de Psicología Básica II (Procesos Cognitivos), Facultad de Psicología, Universidad Complutense de Madrid, Madrid, España
  • 6.
    Servicio de Neurología, Hospital Universitario La Paz, Madrid, España
  • Received: 05 April 2018 Accepted: 11 May 2018 Published: 16 June 2018

  • Vascular pathology and genetic markers such as apolipoprotein E allele ε4 (ApoE ε4) are risk factors for the progression from mild cognitive impairment (MCI) to Alzheimer’s disease (AD). In Panama, a high prevalence of vascular risk factors and an increase in the aging population, generate the need to investigate biomarkers using specific, sensitive, non-invasive and cost-efficient methods that could be used in primary care. The main objective of this study was to explore the association between vascular biomarkers such as intima-media thickness (IMT) and stenosis, ApoΕ ε4 and cognitive function in a sample of older adults, including healthy controls (n = 41), MCI (n = 33), and AD (n = 12). A descriptive and cross-sectional study was conducted. Participants were part of the Panama Aging Research Initiative (PARI), the first prospective study in aging in Panama. Assessments included a neuropsychological battery, ApoΕ ε4 genotyping and a Doppler ultrasound of the left carotid artery to examine the presence of vascular risk factors. Neuropsychological tests were combined to form six cognitive domains: Global cognition, language, visuospatial abilities, learning and memory, attention and executive functions. Multivariable analyses (using age, education, and ApoE ε4 expression as covariates) were conducted. Participants with increased IMT showed poorer performance in memory and those with carotid stenosis showed poorer performance in language, visuospatial abilities and attention, independent of age, education or ApoΕ ε4 expression. The results support the use of vascular markers in cognitive assessments of aged individuals.

    Citation: Diana C. Oviedo, Hector Lezcano, Ambar R. Perez, Alcibiades E. Villarreal, Maria B. Carreira, Baltasar Isaza, Lavinia Wesley, Shantal A. Grajales, Sara Fernandez, Ana Frank, Gabrielle B. Britton. Vascular biomarkers and ApoE4 expression in mild cognitive impairment and Alzheimer’s disease[J]. AIMS Neuroscience, 2018, 5(2): 148-161. doi: 10.3934/Neuroscience.2018.2.148

    Related Papers:

  • Vascular pathology and genetic markers such as apolipoprotein E allele ε4 (ApoE ε4) are risk factors for the progression from mild cognitive impairment (MCI) to Alzheimer’s disease (AD). In Panama, a high prevalence of vascular risk factors and an increase in the aging population, generate the need to investigate biomarkers using specific, sensitive, non-invasive and cost-efficient methods that could be used in primary care. The main objective of this study was to explore the association between vascular biomarkers such as intima-media thickness (IMT) and stenosis, ApoΕ ε4 and cognitive function in a sample of older adults, including healthy controls (n = 41), MCI (n = 33), and AD (n = 12). A descriptive and cross-sectional study was conducted. Participants were part of the Panama Aging Research Initiative (PARI), the first prospective study in aging in Panama. Assessments included a neuropsychological battery, ApoΕ ε4 genotyping and a Doppler ultrasound of the left carotid artery to examine the presence of vascular risk factors. Neuropsychological tests were combined to form six cognitive domains: Global cognition, language, visuospatial abilities, learning and memory, attention and executive functions. Multivariable analyses (using age, education, and ApoE ε4 expression as covariates) were conducted. Participants with increased IMT showed poorer performance in memory and those with carotid stenosis showed poorer performance in language, visuospatial abilities and attention, independent of age, education or ApoΕ ε4 expression. The results support the use of vascular markers in cognitive assessments of aged individuals.


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    [1] Nations U (2017) World Population Aging.
    [2] Nations U (2015) Department of Economic and Social Affairs.
    [3] Hebert LE, Bienias JL, Aggarwal NT, et al. (2010) Change in risk of Alzheimer disease over time. Neurology 75: 786-791. doi: 10.1212/WNL.0b013e3181f0754f
    [4] Palloni A, Pinto-Aguirre G, Pelaez M (2002) Demographic and health conditions of ageing in Latin America and the Caribbean. Int J Epidemiol 31: 762-771. doi: 10.1093/ije/31.4.762
    [5] de la Torre JC (2012) Cerebral hemodynamics and vascular risk factors: setting the stage for Alzheimer's disease. J Alzheimers Dis 32: 553-567. doi: 10.3233/JAD-2012-120793
    [6] Viswanathan A, Rocca WA, Tzourio C (2009) Vascular risk factors and dementia: how to move forward? Neurology 72: 368-374. doi: 10.1212/01.wnl.0000341271.90478.8e
    [7] Iadecola C (2003) Atherosclerosis and neurodegeneration: unexpected conspirators in Alzheimer's dementia. Arterioscler Thromb Vasc Biol 23: 1951-1953. doi: 10.1161/01.ATV.0000102660.99744.85
    [8] Roher AE, Esh C, Kokjohn TA, et al. (2003) Circle of willis atherosclerosis is a risk factor for sporadic Alzheimer's disease. Arterioscler Thromb Vasc Biol 23: 2055-2062. doi: 10.1161/01.ATV.0000095973.42032.44
    [9] Hofman A, Ott A, Breteler MM, et al. (1997) Atherosclerosis, apolipoprotein E, and prevalence of dementia and Alzheimer's disease in the Rotterdam Study. Lancet 349: 151-154. doi: 10.1016/S0140-6736(96)09328-2
    [10] Xiang J, Zhang T, Yang QW, et al. (2013) Carotid artery atherosclerosis is correlated with cognitive impairment in an elderly urban Chinese non-stroke population. J Clin Neurosci 20: 1571-1575. doi: 10.1016/j.jocn.2013.02.026
    [11] Yamaura Y, Watanabe N, Obase K, et al. (2010) Relation between progression of aortic valve sclerosis and carotid intima-media thickening in asymptomatic subjects with cardiovascular risk factors. J Echocardiogr 8: 87-93. doi: 10.1007/s12574-010-0038-9
    [12] Silvestrini M, Viticchi G, Falsetti L, et al. (2011) The role of carotid atherosclerosis in Alzheimer's disease progression. J Alzheimers Dis 25: 719-726. doi: 10.3233/JAD-2011-101968
    [13] Wendell CR, Waldstein SR, Evans MK, et al. (2016) Subclinical carotid atherosclerosis and neurocognitive function in an urban population. Atherosclerosis 249: 125-131. doi: 10.1016/j.atherosclerosis.2016.04.009
    [14] Zeki Al Hazzouri A, Vittinghoff E, Sidney S, et al. (2015) Intima-Media Thickness and Cognitive Function in Stroke-Free Middle-Aged Adults: Findings From the Coronary Artery Risk Development in Young Adults Study. Stroke 46: 2190-2196. doi: 10.1161/STROKEAHA.115.008994
    [15] Romero JR, Beiser A, Seshadri S, et al. (2009) Carotid artery atherosclerosis, MRI indices of brain ischemia, aging, and cognitive impairment: the Framingham study. Stroke 40: 1590-1596. doi: 10.1161/STROKEAHA.108.535245
    [16] Arntzen KA, Schirmer H, Johnsen SH, et al. (2012) Carotid atherosclerosis predicts lower cognitive test results: a 7-year follow-up study of 4,371 stroke-free subjects-the Tromso study. Cerebrovasc Dis 33: 159-165. doi: 10.1159/000334182
    [17] Cervantes S, Samaranch L, Vidal-Taboada JM, et al. (2011) Genetic variation in APOE cluster region and Alzheimer's disease risk. Neurobiol Aging 32: e2107-2117.
    [18] Michaelson DM (2014) APOE epsilon4: the most prevalent yet understudied risk factor for Alzheimer's disease. Alzheimers Dement 10: 861-868. doi: 10.1016/j.jalz.2014.06.015
    [19] Verghese PB, Castellano JM, Holtzman DM (2011) Apolipoprotein E in Alzheimer's disease and other neurological disorders. Lancet Neurol 10: 241-252. doi: 10.1016/S1474-4422(10)70325-2
    [20] Doliner B, Dong C, Blanton SH, et al. (2018) Apolipoprotein E Gene Polymorphism and Subclinical Carotid Atherosclerosis: The Northern Manhattan Study. J Stroke Cerebrovasc Dis 27: 645-652. doi: 10.1016/j.jstrokecerebrovasdis.2017.09.053
    [21] Bangen KJ, Beiser A, Delano-Wood L, et al. (2013) APOE genotype modifies the relationship between midlife vascular risk factors and later cognitive decline. J Stroke Cerebrovasc Dis 22: 1361-1369. doi: 10.1016/j.jstrokecerebrovasdis.2013.03.013
    [22] Filippini N, Ebmeier KP, MacIntosh BJ, et al. (2011) Differential effects of the APOE genotype on brain function across the lifespan. Neuroimage 54: 602-610. doi: 10.1016/j.neuroimage.2010.08.009
    [23] Yusuf S, Hawken S, Ounpuu S, et al. (2004) Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet 364: 937-952. doi: 10.1016/S0140-6736(04)17018-9
    [24] Gracia F, Benzadon A, Gonzalez-Castellon M, et al. (2014) The impact of cerebrovascular disease in Panama. Int J Stroke 9 Suppl A100: 28-30.
    [25] Carrion Donderis M, Moreno Velasquez I, Castro F, et al. (2016) Analysis of mortality trends due to cardiovascular diseases in Panama, 2001-2014. Open Heart 3: e000510. doi: 10.1136/openhrt-2016-000510
    [26] Villarreal AE, Grajales S, O'Bryant SE, et al. (2016) Characterization of Alzheimer's Disease and Mild Cognitive Impairment in Older Adults in Panama. J Alzheimers Dis 54: 897-901. doi: 10.3233/JAD-160402
    [27] Villarreal AE, O'Bryant SE, Edwards M, et al. (2016) Serum-based protein profiles of Alzheimer's disease and mild cognitive impairment in elderly Hispanics. Neurodegener Dis Manag.
    [28] Folstein MF, Folstein SE, McHugh PR (1975) "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12: 189-198.
    [29] Wechsler D (1997) WAIS‐III administration and scoring manual. San Antonio, TX: The Psychological Corporation.
    [30] Reitan RM (1958) Validity of the Trail Making Test as an Indicator or Organic Brain Damage. Perceptual Motor Skills 8: 271–276. doi: 10.2466/pms.1958.8.3.271
    [31] Connor DJ, Schafer k (1998) Administration Manual for the Alzheimer's Disease Assessment Scale. San Diego: Alzheimer's Disease Cooperative Study.
    [32] Kaplan EF, Goodglass H, Weintraub S (1983) The Boston Naming Test (2nd ed.). Philadelphia, PA: Lea & Febiger.
    [33] Spreen O, Benton AL (1977) Neurosensory center comprehensive examination for aphasia: Manual of directions. Vicotria, BC, Canada: Neuropsychology Laboratory, University of Victoria.
    [34] Sunderland T, Hill JL, Mellow AM, et al. (1989) Clock drawing in Alzheimer's disease. A novel measure of dementia severity. J Am Geriatr Soc 37: 725-729.
    [35] Poppelreuter W (1923) Zur Psychologie und Pathologie der optischen Wahrnehmung. Zeitschrift für die Gesamte Neurologie und Psychiatrie 83: 152.
    [36] Lawton MP, Brody EM (1969) Assessment of older people: self-maintaining and instrumental activities of daily living. Gerontologist 9: 179-186. doi: 10.1093/geront/9.3_Part_1.179
    [37] Pfeffer RI, Kurosaki TT, Harrah CH, Jr., et al. (1982) Measurement of functional activities in older adults in the community. J Gerontol 37: 323-329. doi: 10.1093/geronj/37.3.323
    [38] Yesavage JA, Brink TL, Rose TL, et al. (1982) Development and validation of a geriatric depression screening scale: a preliminary report. J Psychiatr Res 17: 37-49. doi: 10.1016/0022-3956(82)90033-4
    [39] Badia X, Roset M, Montserrat S, et al. (1999) La versión española del EuroQol: Descripción y aplicaciones. Medicina Clinica 112 79–86.
    [40] Reisberg B, Ferris SH, de Leon MJ, et al. (1982) The Global Deterioration Scale for assessment of primary degenerative dementia. Am J Psychiatry 139: 1136-1139. doi: 10.1176/ajp.139.9.1136
    [41] Albert MS, DeKosky ST, Dickson D, et al. (2011) 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. Alzheimers Dement 7: 270-279. doi: 10.1016/j.jalz.2011.03.008
    [42] McKhann GM, Knopman DS, Chertkow H, et al. (2011) 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. Alzheimers Dement 7: 263-269. doi: 10.1016/j.jalz.2011.03.005
    [43] Koch W, Ehrenhaft A, Griesser K, et al. (2002) TaqMan systems for genotyping of disease-related polymorphisms present in the gene encoding apolipoprotein E. Clin Chem Lab Med 40: 1123-1131.
    [44] Van Bortel LM (2005) What does intima-media thickness tell us? J Hypertension.
    [45] Grant EG, Benson CB, Moneta GL, et al. (2003) Carotid artery stenosis: gray-scale and Doppler US diagnosis--Society of Radiologists in Ultrasound Consensus Conference. Radiology 229: 340-346. doi: 10.1148/radiol.2292030516
    [46] Cerami C, Dubois B, Boccardi M, et al. (2017) Clinical validity of delayed recall tests as a gateway biomarker for Alzheimer's disease in the context of a structured 5-phase development framework. Neurobiol Aging 52: 153-166. doi: 10.1016/j.neurobiolaging.2016.03.034
    [47] Luna-Lario P, Azcarate-Jimenez L, Seijas-Gomez R, et al. (2015) Proposal for a neuropsychological cognitive evaluation battery for detecting and distinguishing between mild cognitive impairment and dementias. Rev Neurol 60: 553-561.
    [48] Lim SL, Gao Q, Nyunt MS, et al. (2016) Vascular Health Indices and Cognitive Domain Function: Singapore Longitudinal Ageing Studies. J Alzheimers Dis 50: 27-40.
    [49] Cloutier S, Chertkow H, Kergoat MJ, et al. (2015) Patterns of Cognitive Decline Prior to Dementia in Persons with Mild Cognitive Impairment. J Alzheimers Dis 47: 901-913. doi: 10.3233/JAD-142910
    [50] Wisdom NM, Callahan JL, Hawkins KA (2011) The effects of apolipoprotein E on non-impaired cognitive functioning: a meta-analysis. Neurobiol Aging 32: 63-74. doi: 10.1016/j.neurobiolaging.2009.02.003
    [51] Johnston SC, O'Meara ES, Manolio TA, et al. (2004) Cognitive impairment and decline are associated with carotid artery disease in patients without clinically evident cerebrovascular disease. Ann Intern Med 140: 237-247. doi: 10.7326/0003-4819-140-4-200402170-00005
    [52] Vinkers DJ, Stek ML, van der Mast RC, et al. (2005) Generalized atherosclerosis, cognitive decline, and depressive symptoms in old age. Neurology 65: 107-112. doi: 10.1212/01.wnl.0000167544.54228.95
    [53] Mitchell GF, van Buchem MA, Sigurdsson S, et al. (2011) Arterial stiffness, pressure and flow pulsatility and brain structure and function: the Age, Gene/Environment Susceptibility-Reykjavik study. Brain 134: 3398-3407. doi: 10.1093/brain/awr253
    [54] Zhong W, Cruickshanks KJ, Schubert CR, et al. (2014) Pulse wave velocity and cognitive function in older adults. Alzheimer Dis Assoc Disord 28: 44-49. doi: 10.1097/WAD.0b013e3182949f06
    [55] Li X, Ma X, Lin J, et al. (2017) Severe carotid artery stenosis evaluated by ultrasound is associated with post stroke vascular cognitive impairment. Brain Behav 7: e00606. doi: 10.1002/brb3.606
    [56] Wang T, Mei B, Zhang J (2016) Atherosclerotic carotid stenosis and cognitive function. Clin Neurol Neurosurg 146: 64-70. doi: 10.1016/j.clineuro.2016.03.027
    [57] Mathiesen EB, Waterloo K, Joakimsen O, et al. (2004) Reduced neuropsychological test performance in asymptomatic carotid stenosis: The Tromso Study. Neurology 62: 695-701. doi: 10.1212/01.WNL.0000113759.80877.1F
    [58] Nemeth D, Sefcsik T, Nemeth K, et al. (2013) Impaired language production in asymptomatic carotid stenosis. J Neurolinguistics 6: 462–469.
    [59] Rocque BG, Jackson D, Varghese T, et al. (2012) Impaired cognitive function in patients with atherosclerotic carotid stenosis and correlation with ultrasound strain measurements. J Neurol Sci 322: 20-24. doi: 10.1016/j.jns.2012.05.020
    [60] Mataro M, Soriano-Raya JJ, Lopez-Oloriz J, et al. (2014) Cerebrovascular markers in lowered cognitive function. J Alzheimers Dis 42: S383-391. doi: 10.3233/JAD-141443
    [61] Bots ML, van Swieten JC, Breteler MM, et al. (1993) Cerebral white matter lesions and atherosclerosis in the Rotterdam Study. Lancet 341: 1232-1237. doi: 10.1016/0140-6736(93)91144-B
    [62] McDonald CR, Gharapetian L, McEvoy LK, et al. (2012) Relationship between regional atrophy rates and cognitive decline in mild cognitive impairment. Neurobiol Aging 33: 242-253. doi: 10.1016/j.neurobiolaging.2010.03.015
    [63] Moretti DV (2015) Electroencephalography reveals lower regional blood perfusion and atrophy of the temporoparietal network associated with memory deficits and hippocampal volume reduction in mild cognitive impairment due to Alzheimer's disease. Neuropsychiatr Dis Treat 11: 461-470.
    [64] Korolev IO, Symonds LL, Bozoki AC, et al. (2016) Predicting Progression from Mild Cognitive Impairment to Alzheimer's Dementia Using Clinical, MRI, and Plasma Biomarkers via Probabilistic Pattern Classification. PLoS One 11: e0138866. doi: 10.1371/journal.pone.0138866
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