2005nov25 by cuiliqing


									Apathy: a geriatric syndrome?
Apathy is a distinct clinical syndrome characterised by reduced goal-directed
behaviour and a lack of response to external stimuli. It can be seen in
conditions that commonly affect older people, and it is often under diagnosed
because of the overlap of symptoms with depression. In this article, Drs
Ramesh Durairaj and Lisa Fook review the pathology, clinical features and
diagnosis of apathy, and highlight its impact on various medical conditions.

Apathy is defined as a state of diminished motivation, not attributable to
diminished level of consciousness, cognitive impairment, or emotional
distress . It is an executive dysfunction, characterised by a lack of goal-
directed activity and is often mistaken as a type of stress reaction or a
personality trait, resulting in its under diagnosis.

It refers to a collection of features including a reduced interest in
surroundings, difficulty initiating or sustaining an activity, inability to carry out
novel tasks and anhedonia (the inability to experience pleasure).

The condition has far reaching consequences as it can place a tremendous
burden on carers and can drive patients towards institutionalisation. It can
also often be a source of emotional conflict in the family. Carers often
misinterpret the lack of motivation as a sign of emotional disturbance or
protest, which leads to them becoming distressed.

Apathy is distinct from depression and can be observed in many
neuropsychological conditions. Motivation, a diminution of which forms the
basis of apathy, is a complex set of affective and cognitive processes; and
any disorder that affects the above elements can result in a lack of
motivation in various degrees.

Clinical correlates

It is very difficult to distinguish apathy from depression, as their symptoms
can overlap. Some of the symptoms of depression like hypersomnia and
anhedonia are prevalent in apathetic individuals, but others like suicidal
ideation, pessimism and feelings of hopelessness are typically absent.

Traditional diagnostic criteria and rating scales of depression, like the
Hamilton rating scale of depression, consider apathy as an aspect of
depression. However, recent studies have shown that the association
between the two is disease specific and can vary in its degree .
Convergence studies using assessment tools for apathy and the Hamilton
score for depression have demonstrated that Hamilton dysphoric items are
the most important group of symptoms that can discriminate the two (Table

Pioneering work done by Marin et al found that the relationship between
apathy and depression varied among different disease groups . Alzheimer’s
disease (AD) and progressive supranuclear palsy patients usually had high
apathy with low depression scores; whereas patients with left hemispherical
stroke, Parkinson’s disease (PD) and major depression had high depression
with low apathy score. Interestingly, patients with right hemispherical stroke
were the only group to have equal levels of both symptoms.

Neuropathological correlates

Apathy is one of the syndromes associated with damage to the frontal lobes
or subcortical structures like the caudate nucleus, thalamus and the limbic
system that connects with them .

Recent evidence has shifted the emphasis from strict localisation of a site to
circuits involved in executive functioning. The diversity in the expression of
apathy symptoms may reflect the differential involvement of different
neuroanatomical circuits.

The frontal circuit originating in the anterior cingulate gyrus mediates the
goal-directed and motivational behaviour . A lesion in the mesofrontal and
subcortical structures may disrupt normal drive and mood, whereas a lesion
in the dorsolateral frontal cortex or its connections impairs the cognitive base
on which goal-directed behaviours are formed. Involvement of the right
parietotemporal circuit impairs the awareness of the emotional significance
of the events and hence results in failure to integrate emotional
consequences into planning of activities . The dopamine system, especially
the projections between the ventral tegmental area and the nucleus
accumbens, is closely associated with reward and its impairment results in
anhedonia . Apathy can also be a prominent symptom of paramedian
diencephalic syndrome due to bilateral infarcts .

Chemical correlates

There is growing evidence for a link between cholinergic dysfunction and
apathy. Limbic and paralimbic structures are among the regions containing
the highest acetylcholine levels in the brain . It is hypothesised that nucleus
basalis, which is the site of production of choline acetyltranferase, exerts
influence on the cortex in response to motivational and emotional
information conveyed through the limbic system. And if this fails, the result is

Apathy and Alzheimer’s disease

Apathy is arguably the most common behavioural change observed in AD,
occurring in up to 92 per cent of patients but it is under recognised . Apathy
is equally common in men and women with AD. The symptoms are noted
through all stages of
the disease      .

   In some trials (but not all), a higher level of apathy is shown to be
associated with greater cognitive impairment, longer illness duration and
older age       . AD patients with apathy are found to have more severe
impairments in activities of daily living, more severe extrapyramidal signs
and significantly higher frequency of dysthymia .

Evidence suggesting a relationship between apathy and specific cognitive
deficits in AD is beginning to emerge. AD patients with apathy had
significantly lower scores on tests of verbal memory, naming and frontal lobe
functions like verbal fluency than AD patients without apathy. The presence
of both apathy and depression was not associated with greater cognitive
deficits than those with apathy alone. In addition, depression without apathy
was not associated with more severe cognitive impairments compared with
the AD control group (who had neither apathy nor depression), suggesting
that apathy has a more significant impact on the life of AD patients than
depression has .

Apathy and stroke

Apathy is a symptom independent of post stroke depression, as clearly
demonstrated by the Sydney stroke study . In post stroke patients, apathy
was significantly associated with lower Mini Mental State Examination
(MMSE) scores, older age, physical disability, severity of the stroke, lower
levels of verbal intelligence and impaired frontal function test. Depression
was associated with higher MMSE, younger age and a history of psychiatric
illness. Assessment of regional Cerebral Blood Flow (rCBF) in post stroke
patients with a high apathy score showed significantly reduced rCBF in the
right dorsofrontal and left frontotemporal regions .

Frontal lobe syndromes typically present with apathy. The most severe form
of apathy is akinetic mutism, caused by lesions of the cingulate gyrus,
supplementary motor area and mesial motor area. Another prominent
example is seen in bilateral involvement of anterior temporal lobe
and amygdala .

This syndrome resembles Kluver-Bucy syndrome, which results from
bilateral destruction of amygdaloid body and inferior temporal gyrus resulting
in behavioral changes due to affection of the limbic system. There is
physiological evidence that post stroke apathetic patients have impaired
neural processing of novel events, which hampers their rehabilitation .

Apathy and Parkinson’s disease

PD is another example of a subcortical disorder with high prevalence (16 –
42 per cent) of apathy. Apathy has a direct impact on the overall level of
handicap as it reduces participation in age appropriate activities above
and beyond that due to other aspects of the disease. PD patients
displaying a high apathy score have been shown to have significantly
higher levels of impairment of verbal fluency, visual processing, working
memory, encoding strategy and executive cognitive dysfunction.

Evaluation of apathy

Traditionally, apathy has been evaluated along with other measures to
quantify depression or cognition.The Apathy Evaluation Scale (AES) is an
instrument specifically designed to assess apathy and has been validated for
use in older people, stroke, AD, PD, depression and traumatic brain injury.

It rates a person’s thoughts, actions and emotions over the previous four
weeks. It comes as an 18-item or a shorter seven-item instrument and can
be used on either the subject or their carers. The AES has also been shown
to be an appropriate measure of motivation in older adults and it might
predict success in rehabilitation .


There are pharmacological studies reporting improvement in apathy
evaluation scores with psychostimulants, such as methylphenidate
and dextroamphetamine . Dopaminergic drugs like amantadine and
bupropion may be useful in lowering the levels of apathy in conditions
like AD .

Treatment largely depends on the associated neurological disorder.
Cholinergic therapy has shown benefits in treating apathy . Depressed AD
patients with apathy can benefit from an antidepressant with stimulant
properties like bupropion. There is no evidence that symptoms of apathy are
improved by levodopa therapy although there are early indications that the
dopamine D3 agonist pramipexole may be of some value . In the absence
of any meaningful pharmacological treatment, recognition and improvisation
of care-delivery will be the main-stay in management of apathy. Carers may
have to assume new roles as there is diminished initiation and education is
vital to enable that.


Apathy should be carefully distinguished from cognitive decline and
depression. Educating carers on the basis of apathy can alter their
perception of the patient and improve their ability to provide appropriate
care. Further research is needed to investigate the inconsistencies in the
studies done to date and improve our understanding of this ubiquitous

Dr Ramesh Durairaj is a Specialist Registrar and Dr Lisa Fook is a Consultant
Geriatrician at the Royal Liverpool University Hospital


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