Apathy in Neuropsychiatric Disease: Diagnosis, Pathophysiology, and Treatment

Abstract

Apathy is an increasingly recognized concomitant of a broad range of central nervous system disorders. Nevertheless, its nosology, pathogenesis and therapy remain shrouded in confusion and controversy. As yet, there is little consensus regarding methods for detecting apathy, or distinguishing it from depression, or for assessing its severity. Many now regard the apathy syndrome as primarily reflecting a lack of motivation that compromises emotional, cognitive, and overt behavioral function. Even though under-recognized and under-diagnosed, apathy hardly appears uncommon: current epidemiologic studies suggest over 10 million Americans may be affected. Its reported frequency in various neurologic and psychiatric conditions varies widely, from less than 10 to over 80%, reflecting differences in population characteristics and assessment procedures. Often apathy has been associated with such neurodegenerative disorders as Alzheimer's disease, Parkinson's disease, and fronto-temporal dementia. But it also occurs in those with psychiatric disorders such as schizophrenia and major depression. Clinical, neuropathologic, and neuroimaging observations increasingly suggest that apathy reflects dysfunction of frontal-subcortical circuits, especially those linking the ventromedial prefrontal cortex to related regions in the basal ganglia. Therapeutically, numerous small studies suggest that psychostimulants, dopaminergics, and cholinesterase inhibitors may benefit those manifesting this syndrome. However, no adequately powered, randomized controlled trials have reported success and no medication have ever been approved for this disorder. The accelerating pace of current research nevertheless promises to improve our understanding of apathy and to better address the unmet medical needs of those suffering its consequences.

Multidimensional apathy in ALS: validation of the Dimensional Apathy Scale

“…Apathy is defined by decreased motivation towards goal-directed behaviours,1 and occurs as a symptom of a variety of different psychiatric and neurodegenerative diseases 2 3. Studies have shown that apathy occurs in 30–60% of patients with amyotrophic lateral sclerosis (ALS), and is the most prominent behavioural symptom of the disease 4–7.…”

The salience network in the apathy of late‐life depression

“…Apathy is common in depression, affecting more than 30% of individuals with major depression, and is most prevalent in depressed older adults (Chase, 2011, Forsell et al, 1993, Krishnan et al, 1995, Lampe and Heeren, 2004, Mehta et al, 2008). The syndrome of apathy is defined as a primary motivational impairment that in depression results in diminished goal-oriented behavior, lack of intellectual interest, and indifference or flattening of affect (Marin, 1990).…”

“…The syndrome of apathy is defined as a primary motivational impairment that in depression results in diminished goal-oriented behavior, lack of intellectual interest, and indifference or flattening of affect (Marin, 1990). These clinical signs translate into apathetic, depressed patients being poorly engaged in treatment, posing a greater burden to caregivers, and having increased risk of future functional and cognitive impairment (Chase, 2011, Feil et al, 2003, Holtta et al, 2012). In geriatric depression, apathy predicts poor response of depressive symptoms to treatment, chronicity of depression, and disability (Chaturvedi and Sarmukaddam, 1986, Lavretsky et al, 1999, Levkovitz et al, 2011, Marin et al, 2003, Yeager and Hyer, 2008).…”

Agomelatine Improves Apathy in Frontotemporal Dementia

“…At present, no pharmacological therapy is approved for the treatment of apathy [8]; however, the aforementioned possible roles of the dopaminergic system and the prefrontal cortex suggest that the modulation of the dopaminergic mesocortical pathway could represent a reasonable target to try to improve this disabling symptom in subjects with bv-FTD [9]. …”