Magnetic Resonance Imaging Predictors of Treatment Response in Late-Life Depression

Abstract

In older adults, depression not only results in more years lived with disability than any other disease, but it also carries additional risk for suicide, medical comorbidities, and family care-giving burden. Because it can take many months to identify an effective treatment regimen, it is of upmost importance to shorten the window of time and identify early on what medication(s) and dosages will work effectively for individuals suffering from depression. Late-life depression (LLD) has been associated with greater burden of age-related changes, including atrophy, white matter ischemic changes, and alterations in functional connectivity (FC). Depression in midlife has been shown to alter affective reactivity and regulation, and functional magnetic resonance imaging (fMRI) studies in LLD have replicated the same abnormalities. Effective treatment can normalize these alterations. This article provides a review of the current literature using structural and functional neuroimaging to identify magnetic resonance imaging (MRI) predictors of treatment response in LLD. The majority of the literature on structural MRI has focused on the vascular depression hypothesis, and studies support the view that loss of brain volume and white matter integrity is associated with poorer treatment outcomes. Studies using fMRI have reported that lower task-based activity in the prefrontal cortex (PFC) and limbic regions is associated with poorer outcome. These imaging markers may be integrated into clinical decision-making to better treatment outcomes in the future.

Vascular depression consensus report – a critical update

“…Patients with VaDep were suggested to have a distinct clinical and neuropsychological profile and a positive association with hypertension [19], supporting the notion that VaDep represents a unique and valid subtype of LLD [20–22], although this has not been confirmed by others [23–27]. The MRI literature supporting the VaDep hypothesis shows that loss of brain volume and white matter integrity are associated with poor clinical treatment outcomes [28, 29]. Individuals with VaDep are at greater risk to develop cognitive impairment, more likely related to vascular dementia than to Alzheimer’s disease (AD) [30].…”

Altered Functional Magnetic Resonance Imaging Markers of Affective Processing During Treatment of Late-Life Depression

“…6 LLD and major depressive disorder (MDD) at other ages appear to share similar alterations in distinct neural circuits as measured by functional magnetic resonance imaging (fMRI). 7 These changes are primarily localized to frontostriatal pathways and are thought to result in impairments in emotional reactivity and regulation. Specifically, decreased activity has been observed in dorsal cognitive structures such as the dorsolateral prefrontal cortex and dorsal anterior cingulate cortex, and increased activity is seen in limbic and rostral cingulate structures.…”

White Matter Hyperintensity Accumulation During Treatment of Late-Life Depression

“…For these reasons, much of LLD neuroimaging-based research has sought to identify markers that may help decrease the interval between diagnosis and remission. Specifically, multiple groups have sought to establish the presence of any structural or functional imaging markers that could inform clinicians of a patient's likelihood of achieving remission with a given antidepressant trial (Aizenstein et al, 2014).…”