Neuroprotection in late life attention-deficit/hyperactivity disorder: A review of pharmacotherapy and phenotype across the lifespan

Cintya Nirvana Dutta, Leonardo Christov-Moore, Hernando Ombao, Pamela K. Douglas

Research output: Contribution to journalArticlepeer-review


For decades, psychostimulants have been the gold standard pharmaceutical treatment for attention-deficit/hyperactivity disorder (ADHD). In the United States, an astounding 9% of all boys and 4% of girls will be prescribed stimulant drugs at some point during their childhood. Recent meta-analyses have revealed that individuals with ADHD have reduced brain volume loss later in life (>60 y.o.) compared to the normal aging brain, which suggests that either ADHD or its treatment may be neuroprotective. Crucially, these neuroprotective effects were significant in brain regions (e.g., hippocampus, amygdala) where severe volume loss is linked to cognitive impairment and Alzheimer’s disease. Historically, the ADHD diagnosis and its pharmacotherapy came about nearly simultaneously, making it difficult to evaluate their effects in isolation. Certain evidence suggests that psychostimulants may normalize structural brain changes typically observed in the ADHD brain. If ADHD itself is neuroprotective, perhaps exercising the brain, then psychostimulants may not be recommended across the lifespan. Alternatively, if stimulant drugs are neuroprotective, then this class of medications may warrant further investigation for their therapeutic effects. Here, we take a bottom-up holistic approach to review the psychopharmacology of ADHD in the context of recent models of attention. We suggest that future studies are greatly needed to better appreciate the interactions amongst an ADHD diagnosis, stimulant treatment across the lifespan, and structure-function alterations in the aging brain.
Original languageEnglish (US)
JournalFrontiers in Human Neuroscience
StatePublished - Sep 26 2022

Bibliographical note

KAUST Repository Item: Exported on 2022-09-30
Acknowledgements: The authors acknowledge the support provided in part by the Brain & Behavior Research Foundation NARSAD Young Investigator Grant, the K01 NIH Grant (1MH110645), and baseline funds from King Abdullah University of Science and Technology. We appreciate the help given by the Biostatistics Group at King Abdullah University of Science and Technology, University of Central Florida at the Institute for Simulation and Training (IST), UCLA Department of Psychiatry and Biobehavioral Medicine, Brain and Behavior Research Foundation, NARSAD Young Investigator Award, and a K01 Award from the NIMH (K01NIMH and 1MH110645), without which this work would not have been possible. This material is also based upon work supported by the Air Force Office of Scientific Research under award number FA9550-22-1-0000. We also thank Farzad V. Farahani for his contribution to Figure 1 and Aritra Dutta for his contribution to Figures 7, 8. Inclusion of text and images from Cintya N. Dutta’s dissertation was used for this review manuscript.

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry
  • Behavioral Neuroscience
  • Neurology
  • Neuropsychology and Physiological Psychology


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