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Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes · Journal article
Frontiers in Psychiatry · August 19, 2026
Raises a question worth testing. It does not answer one.
This opinion review surveys MRI findings on anxiety disorders in older adults over 15 years, highlighting structural abnormalities (smaller medial orbitofrontal cortex, altered white matter diffusivity, reduced cortical thickness) reported in two small late-life studies, but emphasizes reproducibility challenges and substantial research gaps. The evidence base for late-life anxiety neurobiology remains sparse and underpowered; the authors advocate for larger, multi-site collaborations (e.g. ENIGMA) to confirm preliminary findings.
Narrative opinion review. Published literature on MRI studies of anxiety disorders, with focus on late-life (≥60 years) and generalized anxiety disorder; older adult samples underrepresented in the reviewed literature.. Not specified; review covers international literature from academic search engines..
Of 85 studies on GAD structural and functional abnormalities reviewed by Kolesar et al. (2019), only 8 included older adult participants and only 2 reported structural differences associated with GAD In 30 older adults (aged 60–77), medial orbitofrontal cortex volume showed positive association with worry in GAD but not in asymptomatic peers (Mohlman et al., 2009) In 59 older adults, those with GAD had higher mean diffusivity in left pallidum white matter, lower mean diffusivity in left middle fronto-orbital gyrus, less cortical thickness in medial orbitofrontal cortex and left rostral anterior cingulate cortex, and smaller right inferior frontal gyrus volume, with moderate to large effect sizes (0.54–1.06) but results not surviving multiple comparison corrections (Andreescu et al., 2017)
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Clinicians should recognise that the neurobiological basis of late-life anxiety remains poorly characterised; current evidence from small, underpowered structural imaging studies suggests involvement of orbitofrontal, anterior cingulate, and frontal regions, but findings require replication. The high prevalence of anxiety symptoms in older adults (25–56% depending on setting and measurement) indicates clinical relevance, but research gaps limit mechanistic insight to guide targeted interventions.
This is a narrative opinion review summarizing MRI literature on anxiety in late life over 15 years, identifying neurobiological patterns and research gaps rather than presenting new empirical evidence or a definitive synthesis.
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Quoted from the source exactly as published.
Clinicians should recognise that the neurobiological basis of late-life anxiety remains poorly characterised; current evidence from small, underpowered structural imaging studies suggests involvement of orbitofrontal, anterior cingulate, and frontal regions, but findings require replication. The high prevalence of anxiety symptoms in older adults (25–56% depending on setting and measurement) indicates clinical relevance, but research gaps limit mechanistic insight to guide targeted interventions.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
The number of individuals aged 60 years and older will reach a new global high in 2030 and is projected to continue increasing thereafter (Grinin et al., 2023). With this, research on healthcare, age-related disorders, and mental health in aging has increased. Anxiety disorders are among the most common mental health disorders worldwide (Javid et al., 2023). Accumulating evidence has further suggested that the presentation and symptoms of anxiety likely differ across the lifespan and by sex (Bryant et al., 2013;Shafiee et al., 2024). While rates of most anxiety disorders are reported to decrease with age, rates of generalized anxiety disorder (GAD) have similar rates in both younger and older adults (Andreescu & Lee, 2020). Roughly half of the GAD cases reported in older adults have an onset after 50 years of age (Andreescu & Lee, 2020) and show mixed results on whether prevalence differs by sex (Wolitzky-Taylor et al., 2010;Zhang et al., 2015). Given this, we will focus on GAD within the context of later life stages for this opinion and include some discussion of sex effects when relevant.The presence of clinically relevant anxiety symptoms in older adults has been estimated to vary between 15% and 56% within medical settings (Bryant et al., 2008). Additionally, a recent meta-analysis on studies that implemented anxiety measures specific to geriatric populations (the Geriatric Anxiety Scale and Geriatric Anxiety Inventory), estimated that roughly 25% of older adults experience some degree of anxiety symptoms (Shafiee et al., 2024). Anxiety symptoms in older age have a number of comorbidities including cognitive decline, poorer quality of life, cardiovascular issues, and other mental health issues, especially depression (Andreescu & Lee, 2020;Creed et al., 2002;Dotson et al., 2014;Lenze & Wetherell, 2011;Wolitzky-Taylor et al., 2010). With this, there is a pressing need to better understand the neurological mechanisms behind anxiety disorders at each stage of life. Given that age significantly impacts many other brain systems such as those responsible for executive functioning (Patil et al., 2021) and emotional regulation (Almdahl et al., 2021), there is a pressing need to also better understand the impact of age on the mechanisms linked to high anxiety levels as they may differ throughout the lifespan (see our opinion on that topic in the next section). Neuroimaging techniques provide noninvasive insights into such neural structure and function. In the last 15 years, the number of magnetic resonance imaging (MRI) studies has exploded with a progressive improvement in signal to noise (SNR) ratio, including better spatial and temporal resolutions, which has led to more reliable findings. However, due to the high number of publications, challenges remain in regard to the reproducibility of these neuroimaging findings, and one should remain critical until results can be robustly reproduced, regardless of sequences, head motion, or scanners. Due to the prevalence of neuroimaging research using MRI, we chose to focus on structural and functional (fMRI) MRI findings. In this context, for this special research topic celebrating the 15 th anniversary of Frontiers in Psychiatry, we plan to summarize different and specific aspects of MRI literature from the last 15 years, related to anxiety with a focus on late stages of life. We aim to highlight both the major discoveries made as much as the major challenges that remain to be further investigated. Academic search engines were used to find articles with the following inclusion criteria: must implement MRI measures, be published in the specified timeframe, and investigate some form of anxiety/late-life GAD. While this is far from an exhaustive review, we hope that this opinion will be an eye-opener that provides some guidance and suggestions for the future research of the next 15 years.Already 10 years ago, Andreescu and Varon (2015) noted a lack of neuroimaging research for late-life anxiety/GAD compared to younger populations, particularly for structural imaging. This was further highlighted by a review from Kolesar et al. (2019) that covered brain structural and functional abnormalities in individuals with GAD, regardless of age. This review noted overall structural neural abnormalities in individuals with GAD, including smaller hypothalamic (Terlevic et al., 2013) and hippocampal gray matter volumes (GMV; Moon et al., 2014;Moon & Jeong, 2017), larger amygdala GMV (Etkin et al., 2009), and larger white matter volume in the dorsolateral prefrontal cortex (dlPFC; Moon & Jeong, 2017). However, of the 85 studies included in the review, only eight had older adult participants and only two of these reported structural differences associated with GAD. Both studies included small sample sizes and did not investigate for sex-related effects. The first of these studies, from Mohlman et al. (2009), found that the volume of the medial orbitofrontal cortex (OFC) had a positive association with worry in those with GAD, but not in asymptomatic peers within a sample of 30 older adults aged 60 to 77. The second structural study by Andreescu et al. (2017) included a sample of 59 older adults and found that those with GAD had higher mean diffusivity (MD) in the white matter of the left pallidum and lower MD in the left middle fronto-orbital gyrus. In addition to this, those with GAD had less cortical thickness in the medial OFC and left rostral ACC, and smaller volume of the right inferior frontal gyrus. Unfortunately, none of the results in this study survived corrections for multiple comparisons. With this, moderate to large effect sizes (ranging from 0.54 to 1.06) were noted from the results, leading the researchers to suggest that a larger sample might be able to confirm these results.The Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) collaboration seeks to ameliorate the issue of small sample sizes through worldwide, multi-site collaboration p
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