Apathy in patients with Parkinson*s disease and major depressive disorder, a structural brain imaging study using Voxel Based Morphometry

Background: *Apathy* is a psychopathological syndrome characterised by lack of
interest, desire, emotion and motivation. It is commonly reported in patients
with various neuropsychiatric disorders, such as Parkinson*s disease (PD),
Alzheimer*s disease (AD), and depressive disorder. In PD, the reported
prevalence of apathy ranges between 16.5% and 42% (Isella, Melzi et al. 2002;
Robert, Clairet et al. 2002). Apathy has a great influence on everyday
functioning of patients, and can be a great source of stress to the patients*
relation with his or her partner (Aarsland, Alves et al. 2005; Aarsland,
Bronnick et al. 2006). Moreover, together with other psychiatric and non-motor
symptoms, apathy contributes significantly to disability in PD (Weintraub,
Moberg et al. 2004). Although apathy occurs frequently, it is not frequently
recognized (Rabinstein and Shulman 2000). It is important to gain more
knowledge about the possible causes of apathy in PD, since this may open the
way for treatment of this syndrome and improve the quality of life of both the
patient and their partners. At present, no specific treatment for apathy is
available. Knowledge about the clinical and anatomical correlates of apathy may
result in the development of treatment options and thus improve prognosis. So
far, only a limited number of studies have focussed on apathy in relation to
clinical (mainly neuropsychological) dysfunction. Even less studies have
focused on the neuro-anatomical correlates of apathy. Functional neuro-imaging
studies have shown that hypo-perfusion of the prefrontal brain areas and
cingulate gyrus may play a role in the pathophysiology of apathy (Isella, Melzi
et al. 2002; Pluck and Brown 2002). However, it is presumed that neuronal
networks rather than demarcated brain areas fulfil an important function in the
maintenance of complex behavioural aspects such as initiative, motivation, and
interest, which are all impaired in apathy (Daffner, Mesulam et al. 2000). To
date, hardly any studies have been performed investigating the relation between
apathy and structural changes in the brain. Studies like these, can provide
very useful information about the link between apathy in PD and changes in
white and grey matter. In turn, this may lead to new insights for improved
treatment of apathy in PD.
Relevance for healthcare: Understanding the aetiology of apathy is clinically
very relevant since apathy has a direct impact on the overall functioning of
the patient and his or her environment. It has negative implications for the
prognosis, and contributes significantly to carer burden. Apathy significantly
affects quality of life. Insight into the clinical and neuroanatomical
correlates of apathy will enhance our understanding of this syndrome and may
open the way for the development of potential treatments, thereby increasing
the quality of life for patients and their environment.

Primary objective: the primary objective of the present study is to assess
whether apathy can be linked to structural brain changes (both atrophy of grey
matter, as well as changes in white matter), whether apathy in PD is related to
certain neuropsychological deficits and whether the findings in the PD group
are similar to the AD and depression group. The following specific questions
are of importance:
1. In how far does a differential relation exist between apathy and, especially
prefrontal, brain areas?
2. Does a relation exist between white matter hyper-intensities and apathy?
3. Can apathy be related to specific cognitive complaints?

The present study is a cross-sectional controlled study, including four groups
of participants: 30 PD patients suffering from apathy, 30 PD patients without
apathy, 30 patients suffering from depression, and 30 matched control subjects.
The target intervention will be the imaging session and the neuropsychological
and neuropsychiatric investigation.

Participants will spent approximately 3.5 hours in a single visit to the
research site. The study is aimed at patients suffering from Parkinson*s
disease with and without symptoms of apathy, patients suffering from a
depression and healthy control subjects. It is unlikely that the imaging or the
neuropsychological and neuropsychiatric assessments will cause any harm to
participants. Therefore, participation is not considered to be a risk.