Incidental findings on brain MRI of cognitively normal first-degree descendants of patients with Alzheimer's disease: a cross-sectional analysis from the ALFA (Alzheimer and Families) project

Anna Brugulat-Serrat, Santiago Rojas, Nuria Bargalló, Gerardo Conesa, Carolina Minguillón, Karine Fauria, Nina Gramunt, José Luis Molinuevo, Juan Domingo Gispert, Anna Brugulat-Serrat, Santiago Rojas, Nuria Bargalló, Gerardo Conesa, Carolina Minguillón, Karine Fauria, Nina Gramunt, José Luis Molinuevo, Juan Domingo Gispert

Abstract

Objectives: To describe the prevalence of brain MRI incidental findings (IF) in a cohort of cognitively normal first-degree descendants of patients with Alzheimer's disease (AD).

Design: Cross-sectional observational study.

Setting: All scans were obtained with a 3.0 T scanner. Scans were evaluated by a single neuroradiologist and IF recorded and categorised. The presence of white matter hyperintensities (WMH) was determined with the Fazekas scale and reported as relevant if ≥2.

Participants: 575 participants (45-75 years) underwent high-resolution structural brain MRI. Participants were cognitively normal and scored over the respective cut-off values in all the following neuropsychological tests: Mini-Mental State Examination (≥26), Memory Impairment Screen (≥6), Time Orientation Subtest of the Barcelona Test II (≥68), verbal semantic fluency (naming animals ≥12). Clinical Dementia Rating (CDR) had to be 0.

Results: 155 participants (27.0%) presented with at least one IF. Relevant WMH were present in 7.8% of the participants, and vascular abnormalities, cyst and brain volume loss in 10.7%, 3.1% and 6.9% of the study volunteers, respectively. Neoplastic brain findings were found in 2.4% of participants and within these, meningiomas were the most common (1.7%) and more frequently found in women. A positive correlation between increasing age and the presence of IF was found. Additionally, brain atrophy greater than that expected by age was significantly more prevalent in participants without a parental history of AD.

Conclusions: Brain MRIs of healthy middle-aged participants show a relatively high prevalence of IF even when study participants have been screened for subtle cognitive alterations. Most of our participants are first-degree descendants of patients with AD, and therefore these results are of special relevance for novel imaging studies in the context of AD prevention in cognitively healthy middle-aged participants.

Trial registration number: NCT02198586.

Keywords: Alzheimer's disease; cerebral MRI; healthy; incidental finding; late middle-aged; prevention.

Conflict of interest statement

Competing interests: JLM has provided scientific advice or has been an investigator or data monitoring board member receiving consultancy fees from: Novartis, Pfizer, Eisai, Janssen-Cilag, Lundbeck, Roche, Bayer, Bristol-Myers Squibb, GE Health Care, Merz, MSD, GlaxoSmithKline, Astra-Zeneca, Avid, Lilly, Boehringer-Inghelmein, Biokit, Piramal, IBL and Fujireibio-Europe.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Figures

Figure 1
Figure 1
Incidental findings on brain MRI. (A) White matter hyperintensities. (B) Lacunar infarct. (C) Cavernous malformation. (D) Malformation of venous development. (E) Arachnoid cyst. (F) Meningioma. (G) Non-specific focus of altered signal. (H) Brain volume loss. (I) Chiari malformation type I. (J) Otorhinolaryngology process. (K) Ventriculomegaly suspicious of NPH. (L) Brain stem atrophy.

References

    1. Carrillo MC, Brashear HR, Logovinsky V et al. . Can we prevent Alzheimer's disease? Secondary “prevention” trials in Alzheimer's disease. Alzheimers Dement 2013;9:123–31.e1. 10.1016/j.jalz.2012.12.004
    1. Marcus DS, Wang TH, Parker J et al. . Open Access Series of Imaging Studies (OASIS): cross-sectional MRI data in young, middle aged, nondemented, and demented older adults. J Cogn Neurosci 2007;19:1498–507. 10.1162/jocn.2007.19.9.1498
    1. Morris Z, Whiteley WN, Longstreth WT Jr et al. . Incidental findings on brain magnetic resonance imaging: systematic review and meta-analysis. BMJ 2009;339:b3016 10.1136/bmj.b3016
    1. Nelson CA. Incidental findings in magnetic resonance imaging (MRI) brain research. J Law Med Ethics 2008;36:315–9. 213 10.1111/j.1748-720X.2008.00275.x
    1. Radiologists TRCo. Management of incidental findings detected during research imaging. London: The Royal College of Radiologists, 2011.
    1. van der Lugt A. Incidental findings on brain magnetic resonance imaging. BMJ 2009;339:b3107 10.1136/bmj.b3107
    1. Sandeman EM, Hernandez Mdel C, Morris Z et al. . Incidental findings on brain MR imaging in older community-dwelling subjects are common but serious medical consequences are rare: a cohort study. PLoS ONE 2013;8:e71467 10.1371/journal.pone.0071467
    1. Bos D, Poels MM, Adams HH et al. . Prevalence, clinical management, and natural course of incidental findings on brain MR images: the population-based Rotterdam Scan Study. Radiology 2016;281:507–15. 10.1148/radiol.2016160218
    1. Boutet C, Vassal F, Celle S et al. . Incidental findings on brain magnetic resonance imaging in the elderly: the PROOF study. Brain Imaging Behav 2016. 10.1007/s11682-016-9519-4 doi: 10.1016/j.neuchi.2014.05.006. [Epub ahead of print 20 Sep 2014]
    1. de Leeuw FE, de Groot JC, Achten E et al. . Prevalence of cerebral white matter lesions in elderly people: a population based magnetic resonance imaging study. The Rotterdam Scan Study. J Neurol Neurosurg Psychiatry 2001;70:9–14. 10.1136/jnnp.70.1.9
    1. Sachdev P, Chen X, Wen W. White matter hyperintensities in mid-adult life. Curr Opin Psychiatry 2008;21:268–74. 10.1097/YCO.0b013e3282f945d5
    1. Wang R, Fratiglioni L, Laukka EJ et al. . Effects of vascular risk factors and APOE ε4 on white matter integrity and cognitive decline. Neurology 2015;84:1128–35. 10.1212/WNL.0000000000001379
    1. Vernooij MW, Ikram MA, Tanghe HL et al. . Incidental findings on brain MRI in the general population. N Engl J Med 2007;357:1821–8. 10.1056/NEJMoa070972
    1. Molinuevo JL, Gramunt N, Gispert JD et al. . The ALFA project: a research platform to identify early pathophysiological features of Alzheimer's disease. Alzheimers Demen Transl Res Clin Interv 2016;2:82–92. 10.1016/j.trci.2016.02.003
    1. Vos SJ, Xiong C, Visser PJ et al. . Preclinical Alzheimer's disease and its outcome: a longitudinal cohort study. Lancet Neurol 2013;12:957–65. 10.1016/S1474-4422(13)70194-7
    1. Ritchie CW, Ritchie K. The PREVENT study: a prospective cohort study to identify mid-life biomarkers of late-onset Alzheimer's disease. BMJ Open 2012;2 pii: e001893 10.1136/bmjopen-2012-001893
    1. Coats M, Morris JC. Antecedent biomarkers of Alzheimer's disease: the adult children study. J Geriatr Psychiatry Neurol 2005;18:242–4. 10.1177/0891988705281881
    1. Sager MA, Hermann B, La Rue A. Middle-aged children of persons with Alzheimer's disease: APOE genotypes and cognitive function in the Wisconsin Registry for Alzheimer's Prevention. J Geriatr Psychiatry Neurol 2005;18:245–9. 10.1177/0891988705281882
    1. Ritchie CW, Molinuevo JL, Truyen L et al. . Development of interventions for the secondary prevention of Alzheimer's dementia: the European Prevention of Alzheimer's Dementia (EPAD) project. Lancet Psychiatry 2016;3:179–86. 10.1016/S2215-0366(15)00454-X
    1. Blesa R, Pujol M, Aguilar M et al. . Clinical validity of the ‘mini-mental state’ for Spanish speaking communities. Neuropsychologia 2001;39:1150–7. 10.1016/S0028-3932(01)00055-0
    1. Böhm P, Peña-Casanova J, Gramunt N et al. . [Spanish version of the Memory Impairment Screen (MIS): normative data and discriminant validity]. Neurologia 2005;20:402–11.
    1. Quinones-Ubeda S. Desenvolupament, normalització i validació de la versió estandard de la segona versió del Test Barcelona. Barcelona: Ramon Llull University, 2009.
    1. Peña-Casanova J, Quiñones-Ubeda S, Gramunt-Fombuena N et al. . Spanish Multicenter Normative Studies (NEURONORMA Project): norms for verbal fluency tests. Arch Clin Neuropsychol 2009;24:395–411. 10.1093/arclin/acp042
    1. Morris JC. The Clinical Dementia Rating (CDR): current version and scoring rules. Neurology 1993;43:2412–14. 10.1212/WNL.43.11.2412-a
    1. Fazekas F, Chawluk JB, Alavi A et al. . MR signal abnormalities at 1.5 T in Alzheimer's dementia and normal aging. AJR Am J Roentgenol 1987;149:351–6. 10.2214/ajr.149.2.351
    1. Inzitari D, Simoni M, Pracucci G et al. . Risk of rapid global functional decline in elderly patients with severe cerebral age-related white matter changes: the LADIS study. Arch Intern Med 2007;167:81–8. 10.1001/archinte.167.1.81
    1. Inzitari D, Pracucci G, Poggesi A et al. . Changes in white matter as determinant of global functional decline in older independent outpatients: three year follow-up of LADIS (leukoaraiosis and disability) study cohort. BMJ 2009;339:b2477 10.1136/bmj.b2477
    1. Katzman GL, Dagher AP, Patronas NJ. Incidental findings on brain magnetic resonance imaging from 1000 asymptomatic volunteers. JAMA 1999;282:36–9. 10.1001/jama.282.1.36
    1. Tsushima Y, Taketomi-Takahashi A, Endo K. Prevalence of abnormal findings on brain magnetic resonance (MR) examinations in adult participants of brain docking. BMC Neurol 2005;5:18 10.1186/1471-2377-5-18
    1. Kumar R, Sachdev PS, Price JL et al. . Incidental brain MRI abnormalities in 60- to 64-year-old community-dwelling individuals: data from the Personality and Total Health through Life study. Acta Neuropsychiatr 2008;20:87–90. 10.1111/j.1601-5215.2008.00273.x
    1. Illes J, Rosen AC, Huang L et al. . Ethical consideration of incidental findings on adult brain MRI in research. Neurology 2004;62:888–90. 10.1212/01.WNL.0000118531.90418.89
    1. Weber F, Knopf H. Incidental findings in magnetic resonance imaging of the brains of healthy young men. J Neurol Sci 2006;240:81–4. 10.1016/j.jns.2005.09.008
    1. Kumra S, Ashtari M, Anderson B et al. . Ethical and practical considerations in the management of incidental findings in pediatric MRI studies. J Am Acad Child Adolesc Psychiatry 2006;45:1000–6. 10.1097/01.chi.0000222786.49477.a8
    1. Wardlaw JM, Smith EE, Biessels GJ et al. . Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol 2013;12:822–38. 10.1016/S1474-4422(13)70124-8
    1. Gouw AA, Seewann A, Vrenken H et al. . Heterogeneity of white matter hyperintensities in Alzheimer's disease: post-mortem quantitative MRI and neuropathology. Brain 2008;131(Pt 12):3286–98. 10.1093/brain/awn265
    1. Wardlaw JM, Valdés Hernández MC, Muñoz-Maniega S. What are white matter hyperintensities made of? Relevance to vascular cognitive impairment . J Am Heart Assoc 2015;4:001140 10.1161/JAHA.114.001140
    1. Mineura K, Sasajima H, Kikuchi K et al. . White matter hyperintensity in neurologically asymptomatic subjects. Acta Neurol Scand 1995;92:151–6. 10.1111/j.1600-0404.1995.tb01030.x
    1. Chen X, Wen W, Anstey KJ et al. . Prevalence, incidence, and risk factors of lacunar infarcts in a community sample. Neurology 2009;73:266–72. 10.1212/WNL.0b013e3181aa52ea
    1. Kaufman JL, Karceski S. Risk factors and prevention of lacunar infarcts in 60- to 64-year-olds. Neurology 2009;73:e17–19. 10.1212/WNL.0b013e3181b3ac61
    1. Ge Y, Grossman RI, Babb JS et al. . Age-related total gray matter and white matter changes in normal adult brain. Part I: volumetric MR imaging analysis. AJNR Am J Neuroradiol 2002;23:1327–33.
    1. Fotenos AF, Snyder AZ, Girton LE et al. . Normative estimates of cross-sectional and longitudinal brain volume decline in aging and AD. Neurology 2005;64:1032–9. 10.1212/01.WNL.0000154530.72969.11
    1. Appelman AP, Exalto LG, van der Graaf Y et al. . White matter lesions and brain atrophy: more than shared risk factors? A systematic review. Cerebrovasc Dis 2009;28:227–42. 10.1159/000226774
    1. Baldi I, Engelhardt J, Bonnet C et al. . Epidemiology of meningiomas. Neurochirurgie 2014. 10.1016/j.neuchi.2014.05.006
    1. Goehde SC, Hunold P, Vogt FM et al. . Full-body cardiovascular and tumor MRI for early detection of disease: feasibility and initial experience in 298 subjects. AJR Am J Roentgenol 2005;184:598–611. 10.2214/ajr.184.2.01840598
    1. Lee WJ, Chang LB, Lee YC. Incidental findings on brain MRI. N Engl J Med 2008;358:853–4; author reply 854–5 10.1056/NEJMc073320
    1. Yue NC, Longstreth WT Jr, Elster AD et al. . Clinically serious abnormalities found incidentally at MR imaging of the brain: data from the Cardiovascular Health Study. Radiology 1997;202:41–6. 10.1148/radiology.202.1.8988190
    1. Debette S, Wolf PA, Beiser A et al. . Association of parental dementia with cognitive and brain MRI measures in middle-aged adults. Neurology 2009;73:2071–8. 10.1212/WNL.0b013e3181c67833
    1. Honea RA, Swerdlow RH, Vidoni ED et al. . Reduced gray matter volume in normal adults with a maternal family history of Alzheimer disease. Neurology 2010;74:113–20. 10.1212/WNL.0b013e3181c918cb
    1. Sleegers K, Bettens K, De Roeck A et al. . A 22-single nucleotide polymorphism Alzheimer's disease risk score correlates with family history, onset age, and cerebrospinal fluid Aβ42. Alzheimers Dement 2015;11:1452–60. 10.1016/j.jalz.2015.02.013
    1. Kirschen MP, Jaworska A, Illes J. Subjects’ expectations in neuroimaging research. J Magn Reson Imaging 2006;23:205–9. 10.1002/jmri.20499

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