The neurobiology of apathy in depression and neurocognitive impairment in older adults: a review of epidemiological, clinical, neuropsychological and biological research

Abstract

Apathy is a common condition that involves diminished initiative, diminished interest and diminished emotional expression or responsiveness. It is highly prevalent in the context of a variety of neuropsychiatric disorders and is related to poor health outcomes. Presence of apathy is associated with cognitive and functional decline in dementia. Despite its negative impact on health, there is no definitive treatment for apathy, a clinical reality that may be due in part to lack of knowledge about assessment, neuropsychological features and neurobiological underpinnings. Here, we review and synthesize evidence from clinical, epidemiological, neuropsychological, peripheral biomarker and neuroimaging research. Apathy is a common feature of depression and cognitive disorders and is associated with impairment in executive function. Neuropsychological and neuroimaging studies point to dysfunction of brain circuitry involving the prefrontal cortex, especially the dorsolateral prefrontal cortex circuit, the dorsomedial prefrontal cortex circuit, and the ventromedial prefrontal cortex circuit. However, inconsistent findings, particularly in neuroimaging may be due to heterogeneity of apathy symptoms (with a need to better elucidate subtypes), neuropsychiatric comorbidities, the severity of cognitive impairment and other factors. These factors need to be accounted for in future studies so that biomarker research can make progress. On the whole, the literature on apathy has identified likely neurocognitive, peripheral biomarker and neuroimaging targets for understanding apathy, but also points to the need to address methodological issues that will better inform future studies. In turn, as we learn more about the underpinning of apathy and its subtypes, subsequent research can focus on new neurally based interventions that will strengthen the clinical management of apathy in the context of its comorbidities.

Repetitive transcranial magnetic stimulation for apathy in patients with neurodegenerative conditions, cognitive impairment, stroke, and traumatic brain injury: a systematic review

“…While robust psychometric properties hold significance, it is crucial to take into account additional factors when determining the most suitable apathy rating instrument, such as the type of scale (i.e., general scale or disease−/symptom-specific), specific apathy domains to be measured, the instrument’s sensitivity to detect changes within the required timeframe for treatment effects, information source/rater type, and setting ( 81 ). Furthermore, current literature also recognizes that apathy is not a single construct and may involve not only behavior, cognition and emotions, but also social interactions ( 82 ). Assessing apathy using validated scales is essential due to the diverse range of symptoms observed across several domains and the utilization of multiple measurement scales.…”

Sex‐specific neuropsychological correlates of apathy and depression across neurodegenerative disorders

“…Neurobiologically, the frontostriatal pathways involved in the emergence of apathy and depression are also thought to be responsible for executive functioning (multi-tasking and response inhibition). 14 Indeed, impairments in these domains as well as in verbal learning, verbal fluency, memory, visuospatial reasoning, and fluid intelligence have been associated with apathy and depressive symptoms across neurodegenerative disorders. [4][5][6]8,11,15 Interestingly, in patients with AD, the presence of both apathy and depression together has been associated with greater impairment on tests of abstract thinking when compared to patients with depression or apathy alone.…”

“…Neurobiologically, the frontostriatal pathways involved in the emergence of apathy and depression are also thought to be responsible for executive functioning (multi‐tasking and response inhibition) 14 . Indeed, impairments in these domains as well as in verbal learning, verbal fluency, memory, visuospatial reasoning, and fluid intelligence have been associated with apathy and depressive symptoms across neurodegenerative disorders 4–6,8,11,15 .…”

LRFN5 and OLFM4 as novel potential biomarkers for major depressive disorder: a pilot study

“…Major depressive disorder (MDD) is the most prevalent psychiatric disorder with high mortality and disability, and is one of the main causes of suicide [ 1 , 2 ]. By 2030, depression is predicted to be one of the leading causes of illness burden globally [ 3 ].…”