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Apathy and Its Treatment in Alzheimer's Disease and Other Dementias

Apathy and Its Treatment in Alzheimer's Disease and Other Dementias

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.

Apathy Assessment

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.

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