November 2005, Vol. XXII, Issue 13
Although memory and other cognitive impairments are considered the hallmark features of most dementias, neuropsychiatric abnormalities occur in the majority of such patients (Cohen et al., 1993). Neuropsychiatric symptoms are associated with a rapid course of decline, elevated caregiver distress and overutilization of health care services (Chung and Cummings, 2000; Teri, 1997). Apathy is the most common neuropsychiatric symptom reported among individuals with Alzheimer's disease (AD), affecting approximately 70% of patients in the mild-to-moderate stages (Landes et al., 2001) and increasing in severity as the illness progresses (Mega et al., 1996). Apathy is common in other dementing illnesses as well (e.g., Parkinson's disease [PD], vascular dementia) and may even occur in substantial numbers of patients with mild cognitive impairment (Ready et al., 2003). Apathy is associated with functional impairment and caregiver distress at all levels of disease severity (Boyle et al., 2003; Norton et al., 2001; Rymer et al., 2002).
Apathy is characterized by the loss of initiation and motivation to participate in activities, social withdrawal, and emotional indifference (Marin, 1991). Depression shares some overlapping features (e.g., decreased initiation, social withdrawal), but can be distinguished from apathy primarily on the basis of dysphoria (Marin et al., 1994). Symptoms of dysphoria typically are absent in the apathetic patient, who displays a lack of interest and motivation in the context of emotional indifference. Apathy therefore reflects a syndrome of primary motivational loss, whereas depression reflects a primary mood disturbance.
The Neurobiological Basis
Although the neurobiological basis of apathy remains to be fully elucidated, dysfunction in frontal systems is thought to be important. Three subsystems of the frontal lobes are thought to underlie three distinct neuropsychiatric syndromes: 1) The dorsolateral prefrontal circuit is associated with executive cognitive dysfunction; 2) The lateral orbital prefrontal circuit is associated with disinhibition; and 3) The medial (anterior cingulate) circuit is associated with disorders of motivation, including apathy (Cummings, 1993). In the extreme, large bilateral lesions in the anterior cingulate cortex produce akinetic mutism, a state of profound apathy and amotivational immobility. Neuropathological changes in dementia may result in apathy by affecting this medial frontal circuit, as well as parietotemporal brain regions that subserve motivation and emotion. Cummings and Back (1998) have also proposed that medial frontal and limbic cholinergic deficits may underlie apathy. Dopaminergic pathways that influence frontal-subcortical activation may also play a role in apathy.
A number of instruments have been developed for assessing neuropsychiatric symptoms in individuals with dementia (Table).
The Neuropsychiatric Inventory (NPI) is the most widely used instrument for assessing neuropsychiatric functioning in patients with dementia (Cummings et al., 1994). It is a valid and reliable instrument involving a caregiver interview designed to assess the presence and severity of 10 symptoms: apathy, irritability/lability, dysphoria, delusions, hallucinations, anxiety, agitation/aggression, euphoria, disinhibition and aberrant motor activity. Tekin et al. (2001) reported significant correlations between NPI apathy subscale scores and frontal pathology at autopsy in patients with AD, suggesting that the NPI is useful for this purpose. Moreover, the NPI includes apathy and depression items, which can help clinicians distinguish apathy from depression.