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Alzheimer's Research & Therapy
Published in: Alzheimer's Research & Therapy 1/2020

01-12-2020 | Alzheimer's Disease | Research

Association between retinal thickness and β-amyloid brain accumulation in individuals with subjective cognitive decline: Fundació ACE Healthy Brain Initiative

Authors: Marta Marquié, Sergi Valero, Miguel Castilla-Marti, Joan Martínez, Octavio Rodríguez-Gómez, Ángela Sanabria, Juan Pablo Tartari, Gemma C. Monté-Rubio, Oscar Sotolongo-Grau, Montserrat Alegret, Alba Pérez-Cordón, Natalia Roberto, Itziar de Rojas, Sonia Moreno-Grau, Laura Montrreal, Isabel Hernández, Maitee Rosende-Roca, Ana Mauleón, Liliana Vargas, Carla Abdelnour, Silvia Gil, Ester Esteban-De Antonio, Ana Espinosa, Gemma Ortega, Francisco Lomeña, Javier Pavia, Assumpta Vivas, Miguel Ángel Tejero, Marta Gómez-Chiari, Rafael Simó, Andreea Ciudin, Cristina Hernández, Adelina Orellana, Alba Benaque, Agustín Ruiz, Lluís Tárraga, Mercè Boada, on behalf of the FACEHBI study group

Published in: Alzheimer's Research & Therapy | Issue 1/2020

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Abstract

Background

Optical coherence tomography (OCT) of the retina is a fast and easily accessible tool for the quantification of retinal structural measurements. Multiple studies show that patients with Alzheimer’s disease (AD) exhibit thinning in several retinal layers compared to age-matched controls. Subjective cognitive decline (SCD) has been proposed as a risk factor for progression to AD. There is little data about retinal changes in preclinical AD and their correlation with amyloid-β (Aβ) uptake.

Aims

We investigated the association of retinal thickness quantified by OCT with Aβ accumulation and conversion to mild cognitive impairment (MCI) over 24 months in individuals with SCD.

Methods

One hundred twenty-nine individuals with SCD enrolled in Fundació ACE Healthy Brain Initiative underwent comprehensive neuropsychological testing, OCT scan of the retina and florbetaben (FBB) positron emission tomography (PET) at baseline (v0) and after 24 months (v2). We assessed the association of sixteen retinal thickness measurements at baseline with FBB-PET status (+/−) and global standardize uptake value ratio (SUVR) as a continuous measure at v0 and v2 and their predictive value on clinical status change (conversion to mild cognitive impairment (MCI)) at v2.

Results

Mean age of the sample was 64.72 ± 7.27 years; 62.8% were females. Fifteen participants were classified as FBB-PET+ at baseline and 22 at v2. Every 1 μm of increased thickness in the inner nasal macular region conferred 8% and 6% higher probability of presenting a FBB-PET+ status at v0 (OR = 1.08, 95% CI = 1.02–1.14, p = 0.007) and v2 (OR = 1.06, 95% CI = 1.02–1.11, p = 0.004), respectively. Inner nasal macular thickness also positively correlated with global SUVR (at v0: β = 0.23, p = 0.004; at v2: β = 0.26, p = 0.001). No retinal measurements were associated to conversion to MCI over 24 months.

Conclusions

Subtle retinal thickness changes in the macular region are already present in SCD and correlate with Aβ uptake.
Appendix
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Literature
1.
McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR, Kawas CH, et al. 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. 2011;7(3):263–9.CrossRef
2.
Alzheimer’s Association. 2016 Alzheimer’s disease facts and figures. Alzheimers Dement. 2016;12(4):459–509.CrossRef
3.
Sperling RA, Jack CR, Aisen PS. Testing the right target and right drug at the right stage. Sci Transl Med. 2011;3(111):111cm33.CrossRef
4.
Jessen F, Amariglio RE, van Boxtel M, Breteler M, Ceccaldi M, Chételat G, et al. A conceptual framework for research on subjective cognitive decline in preclinical Alzheimer’s disease. Alzheimers Dement. 2014;10(6):844–52.CrossRef
5.
Reisberg B, Shulman MB, Torossian C, Leng L, Zhu W. Outcome over seven years of healthy adults with and without subjective cognitive impairment. Alzheimers Dement. 2010;6(1):11–24.CrossRef
6.
Ogata S, Hayashi C, Sugiura K, Hayakawa K. Association between subjective memory complaints and impaired higher-level functional capacity in people aged 60 years or older. Arch Gerontol Geriatr. 2015;60(1):201–5.CrossRef
7.
Kryscio RJ, Abner EL, Cooper GE, Fardo DW, Jicha GA, Nelson PT, et al. Self-reported memory complaints: implications from a longitudinal cohort with autopsies. Neurology. 2014;83(15):1359–65.CrossRef
8.
Hyman BT, Phelps CH, Beach TG, Bigio EH, Cairns NJ, Carrillo MC, et al. National Institute on Aging–Alzheimer’s Association guidelines for the neuropathologic assessment of Alzheimer’s disease. Alzheimers Dement. 2012;8(1):1–13.CrossRef
9.
Martínez G, Vernooij RW, Fuentes Padilla P, Zamora J, Flicker L, Bonfill CX. 18F PET with florbetaben for the early diagnosis of Alzheimer’s disease dementia and other dementias in people with mild cognitive impairment (MCI). Cochrane Database Syst Rev. 2017;11:CD012883.PubMed
10.
Mo J-A, Lim J-H, Sul A-R, Lee M, Youn YC, Kim H-J. Cerebrospinal fluid β-amyloid1–42 levels in the differential diagnosis of Alzheimer’s disease—systematic review and meta-analysis. Squitti R, editor. PLoS One. 2015 10(2):e0116802.
11.
Counts SE, Ikonomovic MD, Mercado N, Vega IE, Mufson EJ. Biomarkers for the early detection and progression of Alzheimer’s disease. Neurotherapeutics. 2017;14(1):35–53.CrossRef
12.
Jaffe GJ, Caprioli J. Optical coherence tomography to detect and manage retinal disease and glaucoma. Am J Ophthalmol. 2004;137(1):156–69.CrossRef
13.
den Haan J, Verbraak FD, Visser PJ, Bouwman FH. Retinal thickness in Alzheimer’s disease: a systematic review and meta-analysis. Alzheimer’s Dement Diagn Assess Dis Monit. 2017;6:162–70.
14.
Díaz-Coránguez M, Ramos C, Antonetti DA. The inner blood-retinal barrier: cellular basis and development. Vis Res. 2017;139:123–37.CrossRef
15.
Byerly MS, Blackshaw S. Vertebrate retina and hypothalamus development. Wiley Interdiscip Rev Syst Biol Med. 2009;1(3):380–9.CrossRef
16.
Lamirel C, Newman N, Biousse V. The use of optical coherence tomography in neurology. Rev Neurol Dis. 2009;6(4):E105–20.PubMed
17.
Sadun AA, Bassi CJ. Optic nerve damage in Alzheimer’s disease. Ophthalmology. 1990;97(1):9–17.CrossRef
18.
Koronyo-Hamaoui M, Koronyo Y, Ljubimov AV, Miller CA, Ko MK, Black KL, et al. Identification of amyloid plaques in retinas from Alzheimer’s patients and noninvasive in vivo optical imaging of retinal plaques in a mouse model. Neuroimage. 2011;54(Suppl 1):S204–17.CrossRef
19.
Tas A, Yolcu U, Ilhan A, Gundogan FC. Detection of retinal nerve fibre layer degeneration in patients with Alzheimer’s disease using optical coherence tomography: searching new biomarkers. Acta Ophthalmol. 2015;93(6):e507.CrossRef
20.
Rodriguez-Gomez O, Sanabria A, Perez-Cordon A, Sanchez-Ruiz D, Abdelnour C, Valero S, et al. FACEHBI: a prospective study of risk factors, biomarkers and cognition in a cohort of individuals with subjective cognitive decline. Study rationale and research protocols. J Prev Alzheimer’s Dis. 2017;4(2):100–8.
21.
Boada M, Tárraga L, Hernández I, Valero S, Alegret M, Ruiz A, et al. Design of a comprehensive Alzheimer’s disease clinic and research center in Spain to meet critical patient and family needs. Alzheimers Dement. 2014;10(3):409–15.CrossRef
22.
Abdelnour C, Rodríguez-Gómez O, Alegret M, Valero S, Moreno-Grau S, Sanabria Á, et al. Impact of recruitment methods in subjective cognitive decline. Gifford K, editor. J Alzheimers Dis 2017;57(2):625–632.
23.
Alegret M, Espinosa A, Vinyes-Junqué G, Valero S, Hernández I, Tárraga L, et al. Normative data of a brief neuropsychological battery for Spanish individuals older than 49. J Clin Exp Neuropsychol. 2012;34(2):209–19.CrossRef
24.
Alegret M, Espinosa A, Valero S, Vinyes-Junqué G, Ruiz A, Hernández I, et al. Cut-off scores of a brief neuropsychological battery (NBACE) for Spanish individual adults older than 44 years old. Brucki S, editor. PLoS One. 2013 8(10):e76436.
25.
Alegret M, Rodríguez O, Espinosa A, Ortega G, Sanabria A, Valero S, et al. Concordance between subjective and objective memory impairment in volunteer subjects. J Alzheimers Dis. 2015;48(4):1109–17.CrossRef
26.
Amariglio RE, Frishe K, Olson LE, Wadsworth LP, Lorius N, Sperling RA, et al. Validation of the Face Name Associative Memory Exam in cognitively normal older individuals. J Clin Exp Neuropsychol. 2012;34(6):580–7.CrossRef
27.
Lozoya-Delgado P, Ruiz-Sánchez de León JM, Pedrero-Pérez EJ. Validation of a cognitive complaints questionnaire for young adults: the relation between subjective memory complaints, prefrontal symptoms and perceived stress. Rev Neurol. 2012;54(3):137–50.PubMed
28.
Blesa R, Pujol M, Aguilar M, Santacruz P, Bertran-Serra I, Hernández G, et al. Clinical validity of the “mini-mental state” for Spanish speaking communities. Neuropsychologia. 2001;39(11):1150–7.CrossRef
29.
Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12(3):189–198.
30.
Morris JC. The Clinical Dementia Rating (CDR): current version and scoring rules. Neurology. 1993;43(11):2412–4.CrossRef
31.
De las Cuevas Castresana C., Garcia-Estrada Perez A. G de RJL. “Hospital Anxiety and Depression Scale” y Psicopatología Afectiva. An Psiquiatr. 1995;11(4):126–30.
32.
Bokinni Y, Shah N, Maguire O, Laidlaw DAH. Performance of a computerised visual acuity measurement device in subjects with age-related macular degeneration: comparison with gold standard ETDRS chart measurements. Eye (Lond). 2015;29(8):1085–91.
33.
Pakrou N, Gray T, Mills R, Landers J, Craig J. Clinical comparison of the Icare tonometer and Goldmann applanation tonometry. J Glaucoma. 2008;17(1):43–7.CrossRef
34.
Yang Q, Reisman CA, Wang Z, Fukuma Y, Hangai M, Yoshimura N, et al. Automated layer segmentation of macular OCT images using dual-scale gradient information. Opt Express. 2010;18(20):21293–307.CrossRef
35.
Goozee K, Chatterjee P, James I, Shen K, Sohrabi HR, Asih PR, et al. Elevated plasma ferritin in elderly individuals with high neocortical amyloid-β load. Mol Psychiatry. 2018;23(8):1807–12.CrossRef
36.
Ossenkoppele R, Jansen WJ, Rabinovici GD, Knol DL, van der Flier WM, van Berckel BNM, et al. Prevalence of amyloid PET positivity in dementia syndromes. JAMA. 2015;313(19):1939.CrossRef
37.
Jansen WJ, Ossenkoppele R, Knol DL, Tijms BM, Scheltens P, Verhey FRJ, et al. Prevalence of cerebral amyloid pathology in persons without dementia. JAMA. 2015;313(19):1924.CrossRef
38.
Jack CR, Wiste HJ, Weigand SD, Rocca WA, Knopman DS, Mielke MM, et al. Age-specific population frequencies of cerebral β-amyloidosis and neurodegeneration among people with normal cognitive function aged 50–89 years: a cross-sectional study. Lancet Neurol. 2014;13(10):997–1005.CrossRef
39.
Rodrigue KM, Kennedy KM, Devous MD, Rieck JR, Hebrank AC, Diaz-Arrastia R, et al. Amyloid burden in healthy aging: regional distribution and cognitive consequences. Neurology. 2012;78(6):387–95.CrossRef
40.
Slot RER, Sikkes SAM, Berkhof J, Brodaty H, Buckley R, Cavedo E, et al. Subjective cognitive decline and rates of incident Alzheimer’s disease and non–Alzheimer’s disease dementia. Alzheimers Dement. 2019;15(3):465–76.
41.
Hagen S, Krebs I, Haas P, Glittenberg C, Falkner-Radler CI, Graf A, et al. Reproducibility and comparison of retinal thickness and volume measurements in normal eyes determined with two different Cirrus OCT scanning protocols. Retina. 2011;31(1):41–7.CrossRef
42.
Marquié M, Castilla-Martí M, Valero S, Martínez J, Sánchez D, Hernández I, et al. Visual impairment in aging and cognitive decline: experience in a Memory Clinic. Sci Rep. 2019;9(1):8698.CrossRef
43.
Sánchez D, Castilla-Marti M, Rodríguez-Gómez O, Valero S, Piferrer A, Martínez G, et al. Usefulness of peripapillary nerve fiber layer thickness assessed by optical coherence tomography as a biomarker for Alzheimer’s disease. Sci Rep. 2018;8(1):16345.CrossRef
44.
Golzan SM, Goozee K, Georgevsky D, Avolio A, Chatterjee P, Shen K, et al. Retinal vascular and structural changes are associated with amyloid burden in the elderly: ophthalmic biomarkers of preclinical Alzheimer’s disease. Alzheimers Res Ther. 2017;9(1):13.
45.
O’Bryhim BE, Apte RS, Kung N, Coble D, Van Stavern GP. Association of preclinical Alzheimer disease with optical coherence tomographic angiography findings. JAMA Ophthalmol. 2018;136(11):1242.CrossRef
46.
van de Kreeke JA, Nguyen H-T, den Haan J, Konijnenberg E, Tomassen J, den Braber A, et al. Retinal layer thickness in preclinical Alzheimer’s disease. Acta Ophthalmol. 2019;97(8):798–804.
47.
Snyder PJ, Johnson LN, Lim YY, Santos CY, Alber J, Maruff P, et al. Nonvascular retinal imaging markers of preclinical Alzheimer’s disease. Alzheimer’s Dement Diagn Assess Dis Monit. 2016;4:169–78.
48.
Ascaso FJ, Cruz N, Modrego PJ, Lopez-Anton R, Santabárbara J, Pascual LF, et al. Retinal alterations in mild cognitive impairment and Alzheimer’s disease: an optical coherence tomography study. J Neurol. 2014;261(8):1522–30.
49.
Santos CY, Johnson LN, Sinoff SE, Festa EK, Heindel WC, Snyder PJ. Change in retinal structural anatomy during the preclinical stage of Alzheimer’s disease. Alzheimers Dement. 2018;10:196–209.
50.
Ramirez AI, de Hoz R, Salobrar-Garcia E, Salazar JJ, Rojas B, Ajoy D, et al. The role of microglia in retinal neurodegeneration: Alzheimer’s disease, parkinson, and glaucoma. Front Aging Neurosci. 2017;9:214.CrossRef
51.
Germain F, Pérez-Rico C, Vicente J, Villa P de la. Functional histology of the retina. In: Microscopy: science, technology, applications and education. 2010. p. 914–925.
Metadata
Title
Association between retinal thickness and β-amyloid brain accumulation in individuals with subjective cognitive decline: Fundació ACE Healthy Brain Initiative
Authors
Marta Marquié
Sergi Valero
Miguel Castilla-Marti
Joan Martínez
Octavio Rodríguez-Gómez
Ángela Sanabria
Juan Pablo Tartari
Gemma C. Monté-Rubio
Oscar Sotolongo-Grau
Montserrat Alegret
Alba Pérez-Cordón
Natalia Roberto
Itziar de Rojas
Sonia Moreno-Grau
Laura Montrreal
Isabel Hernández
Maitee Rosende-Roca
Ana Mauleón
Liliana Vargas
Carla Abdelnour
Silvia Gil
Ester Esteban-De Antonio
Ana Espinosa
Gemma Ortega
Francisco Lomeña
Javier Pavia
Assumpta Vivas
Miguel Ángel Tejero
Marta Gómez-Chiari
Rafael Simó
Andreea Ciudin
Cristina Hernández
Adelina Orellana
Alba Benaque
Agustín Ruiz
Lluís Tárraga
Mercè Boada
on behalf of the FACEHBI study group
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Alzheimer's Research & Therapy / Issue 1/2020
Electronic ISSN: 1758-9193
DOI
https://doi.org/10.1186/s13195-020-00602-9

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