Associations between retinal microvasculature and cognition in middle-aged adults with type 1 diabetes without overt neurological symptoms

Iiris Kyläheiko; Aleksi Tarkkonen; Linda Kuusela; Juha Martola; Teemu I Paajanen; Jussi Virkkala; Ward Fickweiler; George L King; Jennifer K Sun; Joni A Turunen; Marika I Eriksson; Per-Henrik Groop; Lena M Thorn; Turgut Tatlisumak; Jukka Putaala; Hanna Jokinen; Daniel Gordin; FinnDiane Study Group

doi:10.1016/j.cccb.2026.100536

Associations between retinal microvasculature and cognition in middle-aged adults with type 1 diabetes without overt neurological symptoms

Cereb Circ Cogn Behav. 2026 Mar 16:10:100536. doi: 10.1016/j.cccb.2026.100536. eCollection 2026.

Authors

Iiris Kyläheiko^{1

2

3

4}, Aleksi Tarkkonen^{3

4

5

6}, Linda Kuusela⁵, Juha Martola⁵, Teemu I Paajanen⁷, Jussi Virkkala⁸, Ward Fickweiler^{9

10}, George L King^{9

10

11}, Jennifer K Sun^{9

10}, Joni A Turunen^{4

12}, Marika I Eriksson^{4

6

13}, Per-Henrik Groop^{4

13

14

15}, Lena M Thorn^{4

6

16}, Turgut Tatlisumak^{17

18}, Jukka Putaala¹⁹, Hanna Jokinen^{1

20}, Daniel Gordin^{3

9

13

21}; FinnDiane Study Group

Affiliations

¹ Department of Psychology, Faculty of Medicine, University of Helsinki, University of Helsinki, PO Box 21 (Haartmaninkatu 3) 00014 University of Helsinki, Helsinki, Finland.
² Department of Neurology, Kymenlaakso Central Hospital, Kotkantie 41, 48210 Kotka, Finland.
³ Minerva Foundation Institute for Medical Research, Biomedicum Helsinki 2U, Tukholmankatu 8, 00290 Helsinki, Finland.
⁴ Folkhälsan Research Center, Biomedicum Helsinki, Haartmaninkatu 8, 00290 Helsinki, Finland.
⁵ HUS Medical Imaging Center, Department of Radiology, Helsinki University Hospital and University of Helsinki, Haartmaninkatu 4, 00029 HUS, Finland.
⁶ Research Program for Clinical and Molecular Metabolism, University of Helsinki, Biomedicum Helsinki, Haartmaninkatu 8, 00290 Helsinki, Finland.
⁷ Occupational Health Unit, Finnish Institute of Occupational Health, Topeliuksenkatu 41 b, 00250 Helsinki, Finland.
⁸ Department of Clinical Neurophysiology, HUS Diagnostic Center, Helsinki University Hospital and University of Helsinki, Haartmaninkatu 4, 00029 HUS, Finland.
⁹ Joslin Diabetes Center, Harvard Medical School, 1 Joslin Place, Boston, MA 02215, USA.
¹⁰ Department of Ophthalmology, Harvard Medical School, 243 Charles Street, Boston, MA 02114, USA.
¹¹ Department of Medicine, Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA.
¹² Department of Ophthalmology, University of Helsinki and Helsinki University Hospital, PO Box 22 (Haartmaninkatu 4) 00014 University of Helsinki, Helsinki, Finland.
¹³ Department of Nephrology, Helsinki University Hospital and University of Helsinki, Biomedicum 2 Helsinki, Tukholmankatu 8, 00029 HUS, Finland.
¹⁴ Department of Diabetes, Central Clinical School, Monash University, Alfred Centre, 99 Commercial Road, Melbourne, VIC 3004, Australia.
¹⁵ Baker Heart and Diabetes Institute, Melbourne, VIC 3004, Australia.
¹⁶ Department of General Practice and Primary Health Care, Helsinki University Hospital and University of Helsinki, Tukholmankatu 8 B, 00290 Helsinki, Finland.
¹⁷ Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Blå stråket 7, plan 3, Sahlgrenska 41345 Gothenburg, Sweden.
¹⁸ Department of Neurology, Sahlgrenska University Hospital, Blå stråket 5, 41345 Gothenburg, Sweden.
¹⁹ Department of Neurology, Helsinki University Hospital and University of Helsinki, Haartmaninkatu 4, 00029 HUS, Finland.
²⁰ Division of Neuropsychology, HUS Neurocenter, Helsinki University Hospital and University of Helsinki, PO box 302 (Paciuksenkatu 21), 00029 HUS, Finland.
²¹ Helsinki Hypertension Center of Excellence, University of Helsinki and Helsinki University Hospital, Haartmaninkatu 8, 00029 HUS, Finland.

Abstract

Aims: Type 1 diabetes is a risk factor for retinal microvascular pathology, cerebral small vessel disease (cSVD), and cognitive deficits. In older individuals with type 1 diabetes, decreased vessel densities of superficial (SCP) and deep (DCP) retinal capillary plexuses have been associated with cognitive impairment. We assessed whether these associations are already evident in midlife among individuals without overt neurological symptoms. We also investigated whether cerebral microbleeds (CMBs) and white matter hyperintensities (WMHs), manifestations of cSVD, modify these associations.

Methods: We measured vessel density of the SCP and DCP, and area of foveal avascular zone (FAZ) in macular 3×3 mm optical coherence tomography angiography (OCTA) images and performed a comprehensive neuropsychological assessment and brain MRI in 153 adults with type 1 diabetes (age 46.4±7.5 years, diabetes duration 30.7±10.1 years).

Results: In univariate analyses, SCP, DCP, and FAZ were related to measures of processing speed and executive functions (standardized β ranged from -0.29 to -0.19, p-values from <0.001 to 0.018). However, after adjusting for age and relevant clinical markers, only association between FAZ and a sensitive working memory task (standardized β=-0.25, p<0.05) remained significant. In interaction analyses, CMBs and WMHs did not modify these associations.

Conclusions: Enlarged FAZ was associated with poorer working memory performance independently of confounding factors. Otherwise, age largely explained the associations between retinal microvascular structure and cognition in middle-aged individuals with type 1 diabetes without any overt neurological symptoms.

Keywords: Cerebral small vessel disease; Cognition; Optical coherence tomography angiography; Retina; Type 1 diabetes.