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May 31, 2022; 98 (22) Research Article

Repeatedly Measured Serum Creatinine and Cognitive Performance in Midlife

The Cardiovascular Risk in Young Finns Study

View ORCID ProfileJuuso O. Hakala, View ORCID ProfileKatja Pahkala, View ORCID ProfileMarkus Juonala, Pia Salo, View ORCID ProfileMika Kähönen, Nina Hutri-Kähönen, View ORCID ProfileTerho Lehtimäki, Tomi P. Laitinen, Eero Jokinen, Leena Taittonen, View ORCID ProfilePäivi Tossavainen, View ORCID ProfileJorma S.A. Viikari, View ORCID ProfileOlli T. Raitakari, View ORCID ProfileSuvi P. Rovio
First published April 11, 2022, DOI: https://doi.org/10.1212/WNL.0000000000200268
Juuso O. Hakala
From the Research Centre of Applied and Preventive Cardiovascular Medicine (J.O.H., K.P., P.S., O.T.R., S.P.R.), University of Turku; Centre for Population Health Research (J.O.H., K.P., P.S., O.T.R., S.P.R.), University of Turku and Turku University Hospital; Paavo Nurmi Centre (J.O.H., K.P.), Sports & Exercise Medicine Unit, Department of Physical Activity and Health, University of Turku; Department of Medicine (M.J., J.S.A.V.), University of Turku; Division of Medicine (M.J., J.S.A.V.), Turku University Hospital; Departments of Clinical Physiology (M.K.) and Pediatrics (N.H.-K.), Tampere University Hospital and Faculty of Medicine and Health Technology, Tampere University; Department of Clinical Chemistry (T.L.), Fimlab Laboratories and Finnish Cardiovascular Research Center–Tampere, Faculty of Medicine and Health Technology, Tampere University; Department of Clinical Physiology (T.P.L.), University of Eastern Finland and Kuopio University Hospital; Department of Paediatric Cardiology (E.J.), Hospital for Children and Adolescents, University of Helsinki; Department of Pediatrics (L.T.), Tampere University Hospital; Department of Pediatrics (L.T., P.T.), PEDEGO Research Unit and Medical Research Center, University of Oulu, and Oulu University Hospital; and Department of Clinical Physiology and Nuclear Medicine (O.T.R.), Turku University Hospital, Finland.
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Katja Pahkala
From the Research Centre of Applied and Preventive Cardiovascular Medicine (J.O.H., K.P., P.S., O.T.R., S.P.R.), University of Turku; Centre for Population Health Research (J.O.H., K.P., P.S., O.T.R., S.P.R.), University of Turku and Turku University Hospital; Paavo Nurmi Centre (J.O.H., K.P.), Sports & Exercise Medicine Unit, Department of Physical Activity and Health, University of Turku; Department of Medicine (M.J., J.S.A.V.), University of Turku; Division of Medicine (M.J., J.S.A.V.), Turku University Hospital; Departments of Clinical Physiology (M.K.) and Pediatrics (N.H.-K.), Tampere University Hospital and Faculty of Medicine and Health Technology, Tampere University; Department of Clinical Chemistry (T.L.), Fimlab Laboratories and Finnish Cardiovascular Research Center–Tampere, Faculty of Medicine and Health Technology, Tampere University; Department of Clinical Physiology (T.P.L.), University of Eastern Finland and Kuopio University Hospital; Department of Paediatric Cardiology (E.J.), Hospital for Children and Adolescents, University of Helsinki; Department of Pediatrics (L.T.), Tampere University Hospital; Department of Pediatrics (L.T., P.T.), PEDEGO Research Unit and Medical Research Center, University of Oulu, and Oulu University Hospital; and Department of Clinical Physiology and Nuclear Medicine (O.T.R.), Turku University Hospital, Finland.
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Markus Juonala
From the Research Centre of Applied and Preventive Cardiovascular Medicine (J.O.H., K.P., P.S., O.T.R., S.P.R.), University of Turku; Centre for Population Health Research (J.O.H., K.P., P.S., O.T.R., S.P.R.), University of Turku and Turku University Hospital; Paavo Nurmi Centre (J.O.H., K.P.), Sports & Exercise Medicine Unit, Department of Physical Activity and Health, University of Turku; Department of Medicine (M.J., J.S.A.V.), University of Turku; Division of Medicine (M.J., J.S.A.V.), Turku University Hospital; Departments of Clinical Physiology (M.K.) and Pediatrics (N.H.-K.), Tampere University Hospital and Faculty of Medicine and Health Technology, Tampere University; Department of Clinical Chemistry (T.L.), Fimlab Laboratories and Finnish Cardiovascular Research Center–Tampere, Faculty of Medicine and Health Technology, Tampere University; Department of Clinical Physiology (T.P.L.), University of Eastern Finland and Kuopio University Hospital; Department of Paediatric Cardiology (E.J.), Hospital for Children and Adolescents, University of Helsinki; Department of Pediatrics (L.T.), Tampere University Hospital; Department of Pediatrics (L.T., P.T.), PEDEGO Research Unit and Medical Research Center, University of Oulu, and Oulu University Hospital; and Department of Clinical Physiology and Nuclear Medicine (O.T.R.), Turku University Hospital, Finland.
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Pia Salo
From the Research Centre of Applied and Preventive Cardiovascular Medicine (J.O.H., K.P., P.S., O.T.R., S.P.R.), University of Turku; Centre for Population Health Research (J.O.H., K.P., P.S., O.T.R., S.P.R.), University of Turku and Turku University Hospital; Paavo Nurmi Centre (J.O.H., K.P.), Sports & Exercise Medicine Unit, Department of Physical Activity and Health, University of Turku; Department of Medicine (M.J., J.S.A.V.), University of Turku; Division of Medicine (M.J., J.S.A.V.), Turku University Hospital; Departments of Clinical Physiology (M.K.) and Pediatrics (N.H.-K.), Tampere University Hospital and Faculty of Medicine and Health Technology, Tampere University; Department of Clinical Chemistry (T.L.), Fimlab Laboratories and Finnish Cardiovascular Research Center–Tampere, Faculty of Medicine and Health Technology, Tampere University; Department of Clinical Physiology (T.P.L.), University of Eastern Finland and Kuopio University Hospital; Department of Paediatric Cardiology (E.J.), Hospital for Children and Adolescents, University of Helsinki; Department of Pediatrics (L.T.), Tampere University Hospital; Department of Pediatrics (L.T., P.T.), PEDEGO Research Unit and Medical Research Center, University of Oulu, and Oulu University Hospital; and Department of Clinical Physiology and Nuclear Medicine (O.T.R.), Turku University Hospital, Finland.
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Mika Kähönen
From the Research Centre of Applied and Preventive Cardiovascular Medicine (J.O.H., K.P., P.S., O.T.R., S.P.R.), University of Turku; Centre for Population Health Research (J.O.H., K.P., P.S., O.T.R., S.P.R.), University of Turku and Turku University Hospital; Paavo Nurmi Centre (J.O.H., K.P.), Sports & Exercise Medicine Unit, Department of Physical Activity and Health, University of Turku; Department of Medicine (M.J., J.S.A.V.), University of Turku; Division of Medicine (M.J., J.S.A.V.), Turku University Hospital; Departments of Clinical Physiology (M.K.) and Pediatrics (N.H.-K.), Tampere University Hospital and Faculty of Medicine and Health Technology, Tampere University; Department of Clinical Chemistry (T.L.), Fimlab Laboratories and Finnish Cardiovascular Research Center–Tampere, Faculty of Medicine and Health Technology, Tampere University; Department of Clinical Physiology (T.P.L.), University of Eastern Finland and Kuopio University Hospital; Department of Paediatric Cardiology (E.J.), Hospital for Children and Adolescents, University of Helsinki; Department of Pediatrics (L.T.), Tampere University Hospital; Department of Pediatrics (L.T., P.T.), PEDEGO Research Unit and Medical Research Center, University of Oulu, and Oulu University Hospital; and Department of Clinical Physiology and Nuclear Medicine (O.T.R.), Turku University Hospital, Finland.
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Nina Hutri-Kähönen
From the Research Centre of Applied and Preventive Cardiovascular Medicine (J.O.H., K.P., P.S., O.T.R., S.P.R.), University of Turku; Centre for Population Health Research (J.O.H., K.P., P.S., O.T.R., S.P.R.), University of Turku and Turku University Hospital; Paavo Nurmi Centre (J.O.H., K.P.), Sports & Exercise Medicine Unit, Department of Physical Activity and Health, University of Turku; Department of Medicine (M.J., J.S.A.V.), University of Turku; Division of Medicine (M.J., J.S.A.V.), Turku University Hospital; Departments of Clinical Physiology (M.K.) and Pediatrics (N.H.-K.), Tampere University Hospital and Faculty of Medicine and Health Technology, Tampere University; Department of Clinical Chemistry (T.L.), Fimlab Laboratories and Finnish Cardiovascular Research Center–Tampere, Faculty of Medicine and Health Technology, Tampere University; Department of Clinical Physiology (T.P.L.), University of Eastern Finland and Kuopio University Hospital; Department of Paediatric Cardiology (E.J.), Hospital for Children and Adolescents, University of Helsinki; Department of Pediatrics (L.T.), Tampere University Hospital; Department of Pediatrics (L.T., P.T.), PEDEGO Research Unit and Medical Research Center, University of Oulu, and Oulu University Hospital; and Department of Clinical Physiology and Nuclear Medicine (O.T.R.), Turku University Hospital, Finland.
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Terho Lehtimäki
From the Research Centre of Applied and Preventive Cardiovascular Medicine (J.O.H., K.P., P.S., O.T.R., S.P.R.), University of Turku; Centre for Population Health Research (J.O.H., K.P., P.S., O.T.R., S.P.R.), University of Turku and Turku University Hospital; Paavo Nurmi Centre (J.O.H., K.P.), Sports & Exercise Medicine Unit, Department of Physical Activity and Health, University of Turku; Department of Medicine (M.J., J.S.A.V.), University of Turku; Division of Medicine (M.J., J.S.A.V.), Turku University Hospital; Departments of Clinical Physiology (M.K.) and Pediatrics (N.H.-K.), Tampere University Hospital and Faculty of Medicine and Health Technology, Tampere University; Department of Clinical Chemistry (T.L.), Fimlab Laboratories and Finnish Cardiovascular Research Center–Tampere, Faculty of Medicine and Health Technology, Tampere University; Department of Clinical Physiology (T.P.L.), University of Eastern Finland and Kuopio University Hospital; Department of Paediatric Cardiology (E.J.), Hospital for Children and Adolescents, University of Helsinki; Department of Pediatrics (L.T.), Tampere University Hospital; Department of Pediatrics (L.T., P.T.), PEDEGO Research Unit and Medical Research Center, University of Oulu, and Oulu University Hospital; and Department of Clinical Physiology and Nuclear Medicine (O.T.R.), Turku University Hospital, Finland.
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Tomi P. Laitinen
From the Research Centre of Applied and Preventive Cardiovascular Medicine (J.O.H., K.P., P.S., O.T.R., S.P.R.), University of Turku; Centre for Population Health Research (J.O.H., K.P., P.S., O.T.R., S.P.R.), University of Turku and Turku University Hospital; Paavo Nurmi Centre (J.O.H., K.P.), Sports & Exercise Medicine Unit, Department of Physical Activity and Health, University of Turku; Department of Medicine (M.J., J.S.A.V.), University of Turku; Division of Medicine (M.J., J.S.A.V.), Turku University Hospital; Departments of Clinical Physiology (M.K.) and Pediatrics (N.H.-K.), Tampere University Hospital and Faculty of Medicine and Health Technology, Tampere University; Department of Clinical Chemistry (T.L.), Fimlab Laboratories and Finnish Cardiovascular Research Center–Tampere, Faculty of Medicine and Health Technology, Tampere University; Department of Clinical Physiology (T.P.L.), University of Eastern Finland and Kuopio University Hospital; Department of Paediatric Cardiology (E.J.), Hospital for Children and Adolescents, University of Helsinki; Department of Pediatrics (L.T.), Tampere University Hospital; Department of Pediatrics (L.T., P.T.), PEDEGO Research Unit and Medical Research Center, University of Oulu, and Oulu University Hospital; and Department of Clinical Physiology and Nuclear Medicine (O.T.R.), Turku University Hospital, Finland.
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Eero Jokinen
From the Research Centre of Applied and Preventive Cardiovascular Medicine (J.O.H., K.P., P.S., O.T.R., S.P.R.), University of Turku; Centre for Population Health Research (J.O.H., K.P., P.S., O.T.R., S.P.R.), University of Turku and Turku University Hospital; Paavo Nurmi Centre (J.O.H., K.P.), Sports & Exercise Medicine Unit, Department of Physical Activity and Health, University of Turku; Department of Medicine (M.J., J.S.A.V.), University of Turku; Division of Medicine (M.J., J.S.A.V.), Turku University Hospital; Departments of Clinical Physiology (M.K.) and Pediatrics (N.H.-K.), Tampere University Hospital and Faculty of Medicine and Health Technology, Tampere University; Department of Clinical Chemistry (T.L.), Fimlab Laboratories and Finnish Cardiovascular Research Center–Tampere, Faculty of Medicine and Health Technology, Tampere University; Department of Clinical Physiology (T.P.L.), University of Eastern Finland and Kuopio University Hospital; Department of Paediatric Cardiology (E.J.), Hospital for Children and Adolescents, University of Helsinki; Department of Pediatrics (L.T.), Tampere University Hospital; Department of Pediatrics (L.T., P.T.), PEDEGO Research Unit and Medical Research Center, University of Oulu, and Oulu University Hospital; and Department of Clinical Physiology and Nuclear Medicine (O.T.R.), Turku University Hospital, Finland.
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Leena Taittonen
From the Research Centre of Applied and Preventive Cardiovascular Medicine (J.O.H., K.P., P.S., O.T.R., S.P.R.), University of Turku; Centre for Population Health Research (J.O.H., K.P., P.S., O.T.R., S.P.R.), University of Turku and Turku University Hospital; Paavo Nurmi Centre (J.O.H., K.P.), Sports & Exercise Medicine Unit, Department of Physical Activity and Health, University of Turku; Department of Medicine (M.J., J.S.A.V.), University of Turku; Division of Medicine (M.J., J.S.A.V.), Turku University Hospital; Departments of Clinical Physiology (M.K.) and Pediatrics (N.H.-K.), Tampere University Hospital and Faculty of Medicine and Health Technology, Tampere University; Department of Clinical Chemistry (T.L.), Fimlab Laboratories and Finnish Cardiovascular Research Center–Tampere, Faculty of Medicine and Health Technology, Tampere University; Department of Clinical Physiology (T.P.L.), University of Eastern Finland and Kuopio University Hospital; Department of Paediatric Cardiology (E.J.), Hospital for Children and Adolescents, University of Helsinki; Department of Pediatrics (L.T.), Tampere University Hospital; Department of Pediatrics (L.T., P.T.), PEDEGO Research Unit and Medical Research Center, University of Oulu, and Oulu University Hospital; and Department of Clinical Physiology and Nuclear Medicine (O.T.R.), Turku University Hospital, Finland.
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Päivi Tossavainen
From the Research Centre of Applied and Preventive Cardiovascular Medicine (J.O.H., K.P., P.S., O.T.R., S.P.R.), University of Turku; Centre for Population Health Research (J.O.H., K.P., P.S., O.T.R., S.P.R.), University of Turku and Turku University Hospital; Paavo Nurmi Centre (J.O.H., K.P.), Sports & Exercise Medicine Unit, Department of Physical Activity and Health, University of Turku; Department of Medicine (M.J., J.S.A.V.), University of Turku; Division of Medicine (M.J., J.S.A.V.), Turku University Hospital; Departments of Clinical Physiology (M.K.) and Pediatrics (N.H.-K.), Tampere University Hospital and Faculty of Medicine and Health Technology, Tampere University; Department of Clinical Chemistry (T.L.), Fimlab Laboratories and Finnish Cardiovascular Research Center–Tampere, Faculty of Medicine and Health Technology, Tampere University; Department of Clinical Physiology (T.P.L.), University of Eastern Finland and Kuopio University Hospital; Department of Paediatric Cardiology (E.J.), Hospital for Children and Adolescents, University of Helsinki; Department of Pediatrics (L.T.), Tampere University Hospital; Department of Pediatrics (L.T., P.T.), PEDEGO Research Unit and Medical Research Center, University of Oulu, and Oulu University Hospital; and Department of Clinical Physiology and Nuclear Medicine (O.T.R.), Turku University Hospital, Finland.
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Jorma S.A. Viikari
From the Research Centre of Applied and Preventive Cardiovascular Medicine (J.O.H., K.P., P.S., O.T.R., S.P.R.), University of Turku; Centre for Population Health Research (J.O.H., K.P., P.S., O.T.R., S.P.R.), University of Turku and Turku University Hospital; Paavo Nurmi Centre (J.O.H., K.P.), Sports & Exercise Medicine Unit, Department of Physical Activity and Health, University of Turku; Department of Medicine (M.J., J.S.A.V.), University of Turku; Division of Medicine (M.J., J.S.A.V.), Turku University Hospital; Departments of Clinical Physiology (M.K.) and Pediatrics (N.H.-K.), Tampere University Hospital and Faculty of Medicine and Health Technology, Tampere University; Department of Clinical Chemistry (T.L.), Fimlab Laboratories and Finnish Cardiovascular Research Center–Tampere, Faculty of Medicine and Health Technology, Tampere University; Department of Clinical Physiology (T.P.L.), University of Eastern Finland and Kuopio University Hospital; Department of Paediatric Cardiology (E.J.), Hospital for Children and Adolescents, University of Helsinki; Department of Pediatrics (L.T.), Tampere University Hospital; Department of Pediatrics (L.T., P.T.), PEDEGO Research Unit and Medical Research Center, University of Oulu, and Oulu University Hospital; and Department of Clinical Physiology and Nuclear Medicine (O.T.R.), Turku University Hospital, Finland.
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Olli T. Raitakari
From the Research Centre of Applied and Preventive Cardiovascular Medicine (J.O.H., K.P., P.S., O.T.R., S.P.R.), University of Turku; Centre for Population Health Research (J.O.H., K.P., P.S., O.T.R., S.P.R.), University of Turku and Turku University Hospital; Paavo Nurmi Centre (J.O.H., K.P.), Sports & Exercise Medicine Unit, Department of Physical Activity and Health, University of Turku; Department of Medicine (M.J., J.S.A.V.), University of Turku; Division of Medicine (M.J., J.S.A.V.), Turku University Hospital; Departments of Clinical Physiology (M.K.) and Pediatrics (N.H.-K.), Tampere University Hospital and Faculty of Medicine and Health Technology, Tampere University; Department of Clinical Chemistry (T.L.), Fimlab Laboratories and Finnish Cardiovascular Research Center–Tampere, Faculty of Medicine and Health Technology, Tampere University; Department of Clinical Physiology (T.P.L.), University of Eastern Finland and Kuopio University Hospital; Department of Paediatric Cardiology (E.J.), Hospital for Children and Adolescents, University of Helsinki; Department of Pediatrics (L.T.), Tampere University Hospital; Department of Pediatrics (L.T., P.T.), PEDEGO Research Unit and Medical Research Center, University of Oulu, and Oulu University Hospital; and Department of Clinical Physiology and Nuclear Medicine (O.T.R.), Turku University Hospital, Finland.
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Suvi P. Rovio
From the Research Centre of Applied and Preventive Cardiovascular Medicine (J.O.H., K.P., P.S., O.T.R., S.P.R.), University of Turku; Centre for Population Health Research (J.O.H., K.P., P.S., O.T.R., S.P.R.), University of Turku and Turku University Hospital; Paavo Nurmi Centre (J.O.H., K.P.), Sports & Exercise Medicine Unit, Department of Physical Activity and Health, University of Turku; Department of Medicine (M.J., J.S.A.V.), University of Turku; Division of Medicine (M.J., J.S.A.V.), Turku University Hospital; Departments of Clinical Physiology (M.K.) and Pediatrics (N.H.-K.), Tampere University Hospital and Faculty of Medicine and Health Technology, Tampere University; Department of Clinical Chemistry (T.L.), Fimlab Laboratories and Finnish Cardiovascular Research Center–Tampere, Faculty of Medicine and Health Technology, Tampere University; Department of Clinical Physiology (T.P.L.), University of Eastern Finland and Kuopio University Hospital; Department of Paediatric Cardiology (E.J.), Hospital for Children and Adolescents, University of Helsinki; Department of Pediatrics (L.T.), Tampere University Hospital; Department of Pediatrics (L.T., P.T.), PEDEGO Research Unit and Medical Research Center, University of Oulu, and Oulu University Hospital; and Department of Clinical Physiology and Nuclear Medicine (O.T.R.), Turku University Hospital, Finland.
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Repeatedly Measured Serum Creatinine and Cognitive Performance in Midlife
The Cardiovascular Risk in Young Finns Study
Juuso O. Hakala, Katja Pahkala, Markus Juonala, Pia Salo, Mika Kähönen, Nina Hutri-Kähönen, Terho Lehtimäki, Tomi P. Laitinen, Eero Jokinen, Leena Taittonen, Päivi Tossavainen, Jorma S.A. Viikari, Olli T. Raitakari, Suvi P. Rovio
Neurology May 2022, 98 (22) e2268-e2281; DOI: 10.1212/WNL.0000000000200268

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Abstract

Background and Objectives Serum creatinine is typically used to assess kidney function. Impaired kidney function and thus high serum creatinine increase the risk of poor cognitive performance. However, serum creatinine might have a nonlinear association because low serum creatinine has been linked to cardiovascular risk and impaired cognitive performance. We studied the longitudinal association between serum creatinine and cognitive performance in midlife.

Methods Since 2001, participants from the Cardiovascular Risk in Young Finns Study were followed up for 10 years. Serum creatinine was measured repeatedly in 2001, 2007, and 2011. Sex-specific longitudinal trajectories for serum creatinine among participants without kidney disease were identified with latent class growth mixture modeling. Overall cognitive function and 4 specific domains—working memory, episodic memory and associative learning, reaction time, and information processing—were assessed with a computerized cognitive test.

Results Four serum creatinine trajectory groups with clinically normal serum creatinine were identified for both men (n = 973) and women (n = 1,204). After 10 years of follow-up, cognitive testing was performed for 2,026 participants 34 to 49 years of age (mean age 41.8 years). In men and women, consistently low serum creatinine was associated with poor childhood school performance, low adulthood education, low adulthood annual income, low physical activity, and smoking. Compared to the men in the low serum creatinine trajectory group, those in the high serum creatinine group had better overall cognitive performance (β = 0.353 SD, 95% CI 0.022–0.684) and working memory (β = 0.351 SD, 95% CI 0.034–0.668), while those in the moderate (β = 0.247 SD, 95% CI 0.026–0.468) or normal (β = 0.244 SD, 95% CI 0.008–0.481) serum creatinine groups had better episodic memory and associative learning. No associations were found for women.

Discussion Our results indicate that in men, compared to low serum creatinine levels, consistently high levels may be associated with better memory and learning function in midlife.

Glossary

BMI=
body mass index;
BP=
blood pressure;
eGFR=
estimated GFR;
GFR=
glomerular filtration rate;
HbA1c=
glycated hemoglobin;
LDL=
low-density lipoprotein;
PAL=
Paired Associates Learning;
RTI=
Reaction Time;
RVP=
Rapid Visual Information Processing;
SWM=
Spatial Working Memory;
YFS=
Young Finns Study

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Submitted and externally peer reviewed. The handling editor was Linda A. Hershey, MD, PhD.

  • CME Course: NPub.org/cmelist

  • Received September 24, 2021.
  • Accepted in final form February 8, 2022.
  • © 2022 American Academy of Neurology
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