The Frontal Systems Behavior Scale (FrSBe) is a newer instrument that was specifically designed to measure behavioral changes related to frontal system dysfunction (Grace and Malloy, 2001). It is a valid, reliable, 46-item questionnaire that assesses the three frontal behavioral syndromes linked to the frontal circuits described earlier: apathy, disinhibition and executive dysfunction. The FrSBe measure of apathy correlates moderately with the NPI apathy rating (Norton et al., 2001) and other ratings of decreased initiation (Ready et al., 2003), but not with the Geriatric Depression Scale (GDS) (Cahn-Weiner et al., 2002). The FrSBe correlates more highly with activities of daily living impairment than the NPI (Boyle et al., 2003; Norton et al., 2001).
The Apathy Evaluation Scale (AES)-Informant version is an 18-item, informant-rated scale that utilizes a four-point Likert-type scale to assess symptoms of apathy (Marin et al., 1991). Although it is widely used, there are very limited guidelines for interpreting AES scores, and Glenn et al. (2002) reported that the AES had poor sensitivity and specificity with respect to the ability to predict the clinician's designation of a patient as apathetic. The Apathy Inventory (IA) is a new instrument that generates scores for emotional blunting, lack of initiation and lack of interest, in addition to a global apathy score (Robert et al., 2002). Preliminary evidence suggests that the caregiver-rated version of the IA is valid and reliable, and total scores on the IA correlate well with the NPI apathy subscale, suggesting high concurrent validity (Robert et al., 2002). A recent review by Malloy and Grace (2005) provides further information on these and related scales.
Cholinesterase inhibitors have some efficacy for reducing the neuropsychiatric symptoms associated with dementia, and apathy is the neuropsychiatric symptom most consistently responsive to treatment (Cummings, 2003; Wynn and Cummings, 2004). Large-scale clinical trials have generally indicated that donepezil(Drug information on donepezil) (Aricept) improves neuropsychiatric functioning, particularly the symptom of apathy (Birks and Harvey, 2003; Feldman et al., 2001; Gauthier et al., 2002; Trinh et al., 2003). A few studies also indicate that galantamine(Drug information on galantamine) (Razadyne) and rivastigmine(Drug information on rivastigmine) (Exelon) may also have beneficial neuropsychiatric effects (Birks et al., 2000). A placebo-controlled, double-blind study evaluated the effects of galantamine in AD patients with cerebrovascular disease and probable vascular dementia (Erkinjuntti, 2002). Researchers found that galantamine was associated with a significant reduction in apathy and anxiety over six-month follow-up. Dartigues et al. (2002) found that rivastigmine resulted in improvement in apathy, irritability, delusions and anxiety in patients with mild-to-moderate AD over a six-month follow-up.
Preliminary evidence also supports the use of activating pharmacologic agents for treating apathy in patients with dementia (Marin et al., 1995). Psychostimulants such as methylphenidate(Drug information on methylphenidate) and dextroamphetamine (Dexedrine, DextroStat) have been shown to reduce symptoms of apathy in case series of patients with AD, PD or cerebrovascular disease (Chatterjee and Fahn, 2002; Galynker et al., 1997; Jansen et al., 2001). Given the phenomenological overlap between apathy and depression, nondepressed dementia patients with apathy may also benefit from the use of antidepressants with stimulant properties. Some evidence suggests that dopaminergic agents may also be useful for reducing apathy, perhaps through enhancement of the functioning of frontostriatal circuits (Corcoran et al., 2004; Muller and von Cramon, 1994; Newburn and Newburn, 2005). Controlled clinical trials are needed to demonstrate convincingly the effectiveness of stimulants, antidepressants and dopaminergic agents in treating apathy in dementia. Additional research is needed to determine the magnitude and duration of positive effect and ensure that reductions in apathy are not accompanied by increases in agitation, psychosis or other side effects. Our research group is currently conducting a double-blind, National Institute on Aging-sponsored study comparing cholinesterase inhibitors alone to cholinesterase inhibitors plus modafinil(Drug information on modafinil) (Provigil) in the treatment of apathy.
Combined pharmacological-behavioral approaches have consistently been shown to be more effective than pharmacologic treatments alone in a wide variety of disorders, including depression. In dementia populations, behavior therapy and applied behavioral analysis techniques have been used successfully to improve such diverse problems as incontinence, agitation and aggression (Teri and Gallagher-Thompson, 1991). Although apathy has not been specifically addressed using behavioral interventions to date, evidence suggests that behavioral interventions are effective for treating depression in patients with AD and their caregivers (Teri et al., 1997). Behavioral interventions in dementia have also resulted in improved patient health and lower caregiver burden (Teri et al., 2003). We recently completed a controlled trial of the effectiveness of a novel caregiver-based behavioral training program for reducing apathy in patients with AD and reducing stress among their caregivers. Preliminary findings suggest that behavioral intervention benefited patients with AD and their caregivers (Boyle et al., 2004). Further research examining the benefits of combined, pharmacological-behavioral interventions is needed.
Summary and Conclusions