Apathy symptoms may identify older patients who are at increased risk of developing dementia, a Dutch prospective cohort study has found.

Data were obtained from the Prevention of Dementia by Intensive Vascular Care trial. Participants were aged 70-78 years, resident in the community and free from dementia at baseline.

The 15-item Geriatric Depression Scale (GDS) was used to identify symptoms of apathy (3 items) and depression (12 items). The three apathy questions were:

• Have you dropped many of your activities and interests?

• Do you prefer to stay at home, rather than going out and doing new things?

• Do you feel full of energy?

Participants were followed up at two-yearly intervals over a period of six to eight years. A total of 3,427 participants completed follow-up and were included in the analysis. Incident dementia was diagnosed clinically using DSM IV criteria and confirmed by an independent adjudication committee.

Overall, 232 (6.8%) of the participants developed dementia. Both apathy symptoms hazard ratio (HR) per symptom 1.28 (95% CI: 1.12-1.45) and depressive symptoms HR 1.12 (95% CI: 1.05-1.19) were associated with incident dementia.

Isolated apathy symptoms (< 2 concurrent depressive symptoms) and isolated depressive symptoms (< 2 apathy symptoms) were also associated with dementia; HR 1.26 (95% CI: 1.06-1.49) and HR 1.16 (95% CI: 1.03-1.31) respectively.

Following adjustment for age, sex, MMSE score, disability and cardiovascular history, apathy symptoms remained significantly associated with dementia HR 1.21 (95% CI: 1.06-1.40) whereas depressive symptoms did not. The association between depressive symptoms and dementia was also lost when the GDS item on memory impairment was removed.

Further analysis suggested that the associations with incident dementia were stronger in the short term, which would suggest that apathy and depressive symptoms are prodromal features of dementia rather than risk factors. A recent study which looked at retrospective trajectories of depressive symptoms came to the same conclusion.¹

Apathy is defined as a lack of motivation not attributable to emotional distress, cognitive impairment or a reduced level of consciousness.2 The diagnostic criteria require the presence of symptoms from at least two of the three dimensions of apathy, namely: goal directed behaviour (e.g. not starting conversations, doing basic tasks), cognition (e.g. lack of interest in recent news or family affairs) and emotion (e.g. loss of emotional responsiveness to events). These symptoms should cause significant functional impairment.³ Apathy is distinguished from depression by the absence of dysphoria (low mood, dissatisfaction with life) and feelings of hopelessness, helplessness or worthlessness, which are covered by 7 and 3 of the GDS-15 items respectively.⁴

Although the three apathy items of the GDS are increasingly being used as a research measure of apathy, the low reported sensitivity, using a cut-off of  ≥ 2, does not support their use as a screening tool.⁵

A further difficulty is the low prevalence of clinical apathy in the general population e.g. only 1.4% of cognitively unimpaired older individuals from a US population.6 In this population group the PPV would only be 3.5%.

The authors conclude:

‘Since depressive symptoms other than memory complaints did not seem to be related to dementia risk, apathy symptoms may be better suited to alert general practitioners to vulnerable persons who could benefit from a more active caregiving approach.’

Compared with those with no symptoms, participants with all three apathy symptoms had approximately double the hazard of developing dementia. However, the absolute risk increase is low, few screen-positive patients will have clinical apathy and there are as yet no treatments with proven efficacy.⁷

Dr Phillip Bland