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Hemodynamic latency is associated with reduced intelligence across the lifespan: an fMRI DCM study of aging, cerebrovascular integrity, and cognitive ability

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Abstract

Changes in neurovascular coupling are associated with both Alzheimer’s disease and vascular dementia in later life, but this may be confounded by cerebrovascular risk. We hypothesized that hemodynamic latency would be associated with reduced cognitive functioning across the lifespan, holding constant demographic and cerebrovascular risk. In 387 adults aged 18–85 (mean = 48.82), dynamic causal modeling was used to estimate the hemodynamic response function in the left and right V1 and V3-ventral regions of the visual cortex in response to a simple checkerboard block design stimulus with minimal cognitive demands. The hemodynamic latency (transit time) in the visual cortex was used to predict general cognitive ability (Full-Scale IQ), controlling for demographic variables (age, race, education, socioeconomic status) and cerebrovascular risk factors (hypertension, alcohol use, smoking, high cholesterol, BMI, type 2 diabetes, cardiac disorders). Increased hemodynamic latency in the visual cortex predicted reduced cognitive function (p < 0.05), holding constant demographic and cerebrovascular risk. Increased alcohol use was associated with reduced overall cognitive function (Full Scale IQ 2.8 pts, p < 0.05), while cardiac disorders (Full Scale IQ 3.3 IQ pts; p < 0.05), high cholesterol (Full Scale IQ 3.9 pts; p < 0.05), and years of education (2 IQ pts/year; p < 0.001) were associated with higher general cognitive ability. Increased hemodynamic latency was associated with reduced executive functioning (p < 0.05) as well as reductions in verbal concept formation (p < 0.05) and the ability to synthesize and analyze abstract visual information (p < 0.01). Hemodynamic latency is associated with reduced cognitive ability across the lifespan, independently of other demographic and cerebrovascular risk factors. Vascular health may predict cognitive ability long before the onset of dementias.

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Data availability

The data that support the findings of this study are openly available in Collaborative Informatics and Neuroimaging Suite (COINS) at https://coins.trendscenter.org, reference number NKI-RS.

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Authors and Affiliations

  1. Department of Psychiatry and Biobehavioral Sciences, University of California, 760 Westwood Plaza, Suite 28-224, Los Angeles, 90095, USA

    Ariana E. Anderson, Mirella Diaz-Santos, Spencer Frei, Bianca H. Dang, Pamela K. Douglas, Robert M. Bilder, Usha Nookala & Susan Y. Bookheimer

  2. Department of Statistics, University of California, Los Angeles, USA

    Ariana E. Anderson, Spencer Frei, Pashmeen Kaur & Mahtash Esfandiari

  3. Department of Statistics, Ohio State University, Columbus, USA

    Pashmeen Kaur

  4. Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA, USA

    Patrick Lyden

  5. Department of Radiology, University of California, San Diego, USA

    Richard Buxton

  6. Institute for Simulation and Training, University of Central Florida, Orlando, USA

    Pamela K. Douglas

  7. Institute of Neurology, University College London, London, UK

    Karl J. Friston

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  1. Ariana E. Anderson
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Correspondence to Ariana E. Anderson.

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Conflict of interest

The Authors have declared that there are no conflicts of interest in relation to the subject of this study. The dataset was originally collected at the Nathan Kline Institute (NKI). All NKI subjects provided written informed consent after receiving a complete description of the study; this study was approved by the Institutional Review Board and adheres to US Federal Policy for the Protection of Human Subjects. Institutional Review Board Approval was obtained for this project at the Nathan Kline Institute (Phase I #226781 and Phase II #239708) and at Montclair State University (Phase I #000983A and Phase II #000983B). Funding: This work was supported by the Burroughs Wellcome Fund and the National Institutes of Health (NIH) – (National Institute of Mental Health UL1DE019580, R01MH101478, PL1MH083271 to RB, R03MH106922 to RB and AA; by the National Institute on Aging (NIA) K25AG051782 to AA, and by a Research Supplement to Promote Diversity in Health-Related Research Award U01 AG052564-01 from NIA to MDS. Ariana E Anderson, Ph.D., holds a Career Award at the Scientific Interface from BWF. PL is supported by grants R01NS075930 and U01 NS088312 from the National Institute of Neurological Disorders and Stroke, and by the Carmen and Louis Warschaw Family Chair in Neurology, and by the Lippman Family Foundation.

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Anderson, A.E., Diaz-Santos, M., Frei, S. et al. Hemodynamic latency is associated with reduced intelligence across the lifespan: an fMRI DCM study of aging, cerebrovascular integrity, and cognitive ability. Brain Struct Funct 225, 1705–1717 (2020). https://doi.org/10.1007/s00429-020-02083-w

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