Associations of inner retinal layers with risk of incident dementia: An individual participant data analysis of four prospective cohort studies

Frank C T van der Heide; Anthony Khawaja; Tos T J M Berendschot; Thomas J Littlejohns; Elżbieta Kuźma; Robert Luben; Praveen J Patel; Paul J Foster; Carroll Webers; Bram Kroon; Carla van der Kallen; Martinus van Dongen; Simone Eussen; Casper Schalkwijk; Hans Bosma; Sebastian Koehler; Miranda Schram; Gabriëlla Blokland; David Linden; Anke Wesselius; Maastricht Study Consortium; Geir Bertelsen; Therese von Hanno; Bente Johnsen; Henrik Schirmer; Sara C L Rebouças; Leslie Grasset; Cécile Delcourt; Catherine Helmer; UK Biobank Eye & Vision Consortium; European Eye Epidemiology (E3) Consortium; Coen D A Stehouwer

doi:10.1002/alz.13167

Associations of inner retinal layers with risk of incident dementia: An individual participant data analysis of four prospective cohort studies

Frank C T van der Heide^*, Anthony Khawaja, Tos T J M Berendschot, Thomas J Littlejohns, Elżbieta Kuźma, Robert Luben, Praveen J Patel, Paul J Foster, Carroll Webers, Bram Kroon, Carla van der Kallen, Martinus van Dongen, Simone Eussen, Casper Schalkwijk, Hans Bosma, Sebastian Koehler, Miranda Schram, Gabriëlla Blokland, David Linden, Anke WesseliusMaastricht Study Consortium, Geir Bertelsen, Therese von Hanno, Bente Johnsen, Henrik Schirmer, Sara C L Rebouças, Leslie Grasset, Cécile Delcourt, Catherine Helmer, UK Biobank Eye & Vision Consortium, European Eye Epidemiology (E3) Consortium, Coen D A Stehouwer

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

INTRODUCTION: Our main objective was to investigate whether retinal neurodegeneration, estimated from lower thickness of inner retinal layers, was associated with incident all-cause dementia and Alzheimer's disease (AD).

METHODS: We performed an individual participant data meta-analysis using unpublished data from four prospective cohort studies with a total of 69,955 participants (n = 1087 cases of incident all-cause dementia; n = 520 cases incident AD; follow-up time median [interquartile range] 11.3 [8.8-11.5] years).

RESULTS: General baseline characteristics of the study population were mean (standard deviation) age, 58.1 (8.8) years; 47% women. After adjustment, lower baseline macular retinal nerve fiber layer thickness was significantly associated with a 10% and 11% higher incidence of all-cause dementia and AD, respectively. Lower baseline macular ganglion cell-inner plexiform layer thickness was not significantly associated with these outcomes.

DISCUSSION: These findings suggest that retinal neurodegeneration precedes the onset of clinical dementia. Retinal imaging tools may be informative biomarkers for the study of the early pathophysiology of dementia.

Original language	English
Article number	13167
Pages (from-to)	211-220
Number of pages	10
Journal	Alzheimer's & Dementia
Volume	20
Issue number	1
Early online date	8 Aug 2023
DOIs	https://doi.org/10.1002/alz.13167
Publication status	Published - 2024

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10.1002/alz.13167Licence: CC BY-NC-ND

Cite this

van der Heide, F. C. T., Khawaja, A., Berendschot, T. T. J. M., Littlejohns, T. J., Kuźma, E., Luben, R., Patel, P. J., Foster, P. J., Webers, C., Kroon, B., van der Kallen, C., van Dongen, M., Eussen, S., Schalkwijk, C., Bosma, H., Koehler, S., Schram, M., Blokland, G., Linden, D., ... Stehouwer, C. D. A. (2024). Associations of inner retinal layers with risk of incident dementia: An individual participant data analysis of four prospective cohort studies. Alzheimer's & Dementia, 20(1), 211-220. Article 13167. https://doi.org/10.1002/alz.13167

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title = "Associations of inner retinal layers with risk of incident dementia: An individual participant data analysis of four prospective cohort studies",

abstract = "INTRODUCTION: Our main objective was to investigate whether retinal neurodegeneration, estimated from lower thickness of inner retinal layers, was associated with incident all-cause dementia and Alzheimer's disease (AD).METHODS: We performed an individual participant data meta-analysis using unpublished data from four prospective cohort studies with a total of 69,955 participants (n = 1087 cases of incident all-cause dementia; n = 520 cases incident AD; follow-up time median [interquartile range] 11.3 [8.8-11.5] years).RESULTS: General baseline characteristics of the study population were mean (standard deviation) age, 58.1 (8.8) years; 47% women. After adjustment, lower baseline macular retinal nerve fiber layer thickness was significantly associated with a 10% and 11% higher incidence of all-cause dementia and AD, respectively. Lower baseline macular ganglion cell-inner plexiform layer thickness was not significantly associated with these outcomes.DISCUSSION: These findings suggest that retinal neurodegeneration precedes the onset of clinical dementia. Retinal imaging tools may be informative biomarkers for the study of the early pathophysiology of dementia.",

author = "{van der Heide}, {Frank C T} and Anthony Khawaja and Berendschot, {Tos T J M} and Littlejohns, {Thomas J} and El{\.z}bieta Ku{\'z}ma and Robert Luben and Patel, {Praveen J} and Foster, {Paul J} and Carroll Webers and Bram Kroon and {van der Kallen}, Carla and {van Dongen}, Martinus and Simone Eussen and Casper Schalkwijk and Hans Bosma and Sebastian Koehler and Miranda Schram and Gabri{\"e}lla Blokland and David Linden and Anke Wesselius and {Maastricht Study Consortium} and Geir Bertelsen and {von Hanno}, Therese and Bente Johnsen and Henrik Schirmer and Rebou{\c c}as, {Sara C L} and Leslie Grasset and C{\'e}cile Delcourt and Catherine Helmer and {UK Biobank Eye & Vision Consortium} and {European Eye Epidemiology (E3) Consortium} and Stehouwer, {Coen D A}",

note = "{\textcopyright} 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.",

year = "2024",

doi = "10.1002/alz.13167",

language = "English",

volume = "20",

pages = "211--220",

journal = "Alzheimer's & Dementia",

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van der Heide, FCT, Khawaja, A, Berendschot, TTJM, Littlejohns, TJ, Kuźma, E, Luben, R, Patel, PJ, Foster, PJ, Webers, C , Kroon, B , van der Kallen, C, van Dongen, M, Eussen, S , Schalkwijk, C , Bosma, H, Koehler, S, Schram, M , Blokland, G , Linden, D , Wesselius, A, Maastricht Study Consortium, Bertelsen, G, von Hanno, T, Johnsen, B, Schirmer, H, Rebouças, SCL, Grasset, L, Delcourt, C, Helmer, C, UK Biobank Eye & Vision Consortium, European Eye Epidemiology (E3) Consortium & Stehouwer, CDA 2024, 'Associations of inner retinal layers with risk of incident dementia: An individual participant data analysis of four prospective cohort studies', Alzheimer's & Dementia, vol. 20, no. 1, 13167, pp. 211-220. https://doi.org/10.1002/alz.13167

Associations of inner retinal layers with risk of incident dementia: An individual participant data analysis of four prospective cohort studies. / van der Heide, Frank C T; Khawaja, Anthony; Berendschot, Tos T J M et al.
In: Alzheimer's & Dementia, Vol. 20, No. 1, 13167, 2024, p. 211-220.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Associations of inner retinal layers with risk of incident dementia

T2 - An individual participant data analysis of four prospective cohort studies

AU - van der Heide, Frank C T

AU - Khawaja, Anthony

AU - Berendschot, Tos T J M

AU - Littlejohns, Thomas J

AU - Kuźma, Elżbieta

AU - Luben, Robert

AU - Patel, Praveen J

AU - Foster, Paul J

AU - Webers, Carroll

AU - Kroon, Bram

AU - van der Kallen, Carla

AU - van Dongen, Martinus

AU - Eussen, Simone

AU - Schalkwijk, Casper

AU - Bosma, Hans

AU - Koehler, Sebastian

AU - Schram, Miranda

AU - Blokland, Gabriëlla

AU - Linden, David

AU - Wesselius, Anke

AU - Maastricht Study Consortium

AU - Bertelsen, Geir

AU - von Hanno, Therese

AU - Johnsen, Bente

AU - Schirmer, Henrik

AU - Rebouças, Sara C L

AU - Grasset, Leslie

AU - Delcourt, Cécile

AU - Helmer, Catherine

AU - UK Biobank Eye & Vision Consortium

AU - European Eye Epidemiology (E3) Consortium

AU - Stehouwer, Coen D A

PY - 2024

Y1 - 2024

N2 - INTRODUCTION: Our main objective was to investigate whether retinal neurodegeneration, estimated from lower thickness of inner retinal layers, was associated with incident all-cause dementia and Alzheimer's disease (AD).METHODS: We performed an individual participant data meta-analysis using unpublished data from four prospective cohort studies with a total of 69,955 participants (n = 1087 cases of incident all-cause dementia; n = 520 cases incident AD; follow-up time median [interquartile range] 11.3 [8.8-11.5] years).RESULTS: General baseline characteristics of the study population were mean (standard deviation) age, 58.1 (8.8) years; 47% women. After adjustment, lower baseline macular retinal nerve fiber layer thickness was significantly associated with a 10% and 11% higher incidence of all-cause dementia and AD, respectively. Lower baseline macular ganglion cell-inner plexiform layer thickness was not significantly associated with these outcomes.DISCUSSION: These findings suggest that retinal neurodegeneration precedes the onset of clinical dementia. Retinal imaging tools may be informative biomarkers for the study of the early pathophysiology of dementia.

AB - INTRODUCTION: Our main objective was to investigate whether retinal neurodegeneration, estimated from lower thickness of inner retinal layers, was associated with incident all-cause dementia and Alzheimer's disease (AD).METHODS: We performed an individual participant data meta-analysis using unpublished data from four prospective cohort studies with a total of 69,955 participants (n = 1087 cases of incident all-cause dementia; n = 520 cases incident AD; follow-up time median [interquartile range] 11.3 [8.8-11.5] years).RESULTS: General baseline characteristics of the study population were mean (standard deviation) age, 58.1 (8.8) years; 47% women. After adjustment, lower baseline macular retinal nerve fiber layer thickness was significantly associated with a 10% and 11% higher incidence of all-cause dementia and AD, respectively. Lower baseline macular ganglion cell-inner plexiform layer thickness was not significantly associated with these outcomes.DISCUSSION: These findings suggest that retinal neurodegeneration precedes the onset of clinical dementia. Retinal imaging tools may be informative biomarkers for the study of the early pathophysiology of dementia.

U2 - 10.1002/alz.13167

DO - 10.1002/alz.13167

M3 - Article

C2 - 37551793

SN - 1552-5260

VL - 20

SP - 211

EP - 220

JO - Alzheimer's & Dementia

JF - Alzheimer's & Dementia

IS - 1

M1 - 13167

ER -