Cognitive rehabilitation treatment (CRT) in patients with bipolar disorder and cognitive problems.

A bipolar disorder is a chronic and recurring mental disorder, that is
characterized by one or multiple hypomanic or manic episodes, usually altered
with depressive episodes (Kupka & Hilligers, 2012). Bipolar disorder affects
approximately 2% of the Dutch population in life, while the prevalence for the
wider bipolar spectrum [hypomanic without depressive phase, hypomanic less
severe or shorter in duration than specified in the Diagnostic and Statistical
Manual of Mental Disorders (DSM) and the International Statistical
Classification of Disease and Related Health Problems (ICD)] is estimated at 5%
(van der Werf-Eldering, Schouws, Arts & Jabben, 2012). Bipolar disorder is
associated with enhanced disability compared to other prominent chronic
disorders, such as asthma or diabetes (Sajatovic, 2005). Patients with bipolar
disorder experience difficulties in work functioning, a decrease in social
engagement, weaker family relationships, and difficulties in long-term
relationships (Michalak, Yatham, Maxwell, Hale, & Lam, 2007; Bauwens, Tracy,
Pardoen, Elst, & Mendlewicz, 1991; Shapira et al., 1999; Mitchell, Slade, &
Andrews, 2004; Thomas, Nisha, & Varghese, 2016). Cognitive dysfunction in
bipolar disorder is associated with a reduced functional outcome in general
(Depp et al., 2012).
The last two decades, studies exploring cognitive dysfunction in
patients with bipolar disorder increased in number. These studies did not
result in a consistent neuropsychological profile, but consensus was reached;
primarily difficulties regarding executive functioning and memory were
reported. In addition, cognitive dysfunction has also been reported in the
processing speed and concentration domains (Sagar, Sahu, Pattanayak, &
Chatterjee, 2018, Tsitipa & Fountoulakis, 2015). According to Sagar and
colleagues (2018), there are indications that cognitive dysfunction in patients
with bipolar disorder can be regarded as a trait as well as a state. Other
studies suggest that neurodevelopmental factors play a role in cognitive
dysfunction in patients with bipolar disorder (Bora & Özerdem, 2017; Kloiber et
al., 2020).
Studies estimated the prevalence of cognitive dysfunction in patients
with bipolar disorder around 40 to 60 percent, which remain also in the
euthymic phase (Martino, 2008; Martinez-Aran et al., 2009). Cognitive
dysfunction in the euthymic phase of the bipolar disorder is considered an
important predictor for limitations in psychosocial functioning (Depp et al.,
2012; Zarate, Jr., Tohen, Land, & Cavanagh, 2000). One intervention that offers
a treatment option for cognitive dysfunction is neuropsychological treatment.

Neuropsychological treatment focuses on: *The treatment of patients
with cognitive, emotional, social and / or behavioural consequences of brain
injury and / or treatment of the system of these patients, aimed at learning
how to deal with these consequences as well as possible.* (Van Heugten,
Bertens, & Spikman, 2017). This kind of treatment includes training of mental
processes and tasks (Anaya et al., 2012; MacQueen & Memedovich, 2016). Some
studies show positive effects of neuropsychological treatment on cognitive
dysfunction in patients with acquired brain injury (Vaessen & van Balen, 2014;
Anaya et al., 2012). However, studies that focus on these kinds of treatment
are limited since they mostly focus on patients with acquired brain injury.
Nevertheless, cognitive dysfunctions in people with mental disorders are
comparable to both the cognitive and the emotional, social and / or behavioural
consequences in people with brain damage (Konrad et al., 2010).
Neuropsychological tests are valuable to gain insight into the strengths and
weaknesses profile surrounding cognitive dysfunction, but do not identify
problems in daily life due to the cognitive symptoms (Wilson, 2003).
The best of our knowledge, studies exploring the effect of
neuropsychological treatment in patients with bipolar disorder lack. However, a
recent case-study exploring the effect of cognitive rehabilitation therapy
(CRT) showed positive results regarding executive functioning in a patient with
bipolar disorder (De Vroege et al., under review).
These first results suggest that CRT offers an option of treatment that
improves cognitive symptoms in patients with bipolar disorder. CRT improves
cognitive functioning by training previously acquired skills and learning
alternative strategies (Tsaousides & Gordon, 2009) CRT was primarily developed
for patients with cognitive impairment after stroke or traumatic brain damage
(van Heugten, Caldenhove, Crutsen, & Winkens, 2019) but may also be beneficial
for patients with bipolar disorder.
GGz Breburg has opted to offer CRT to patients with bipolar disorder in
order to improve their cognitive functioning. Because cognitive dysfunction is
seen as an important predictor for limitations in psychosocial functioning.
Psychosocial functioning may improve as a result of improved cognitive
functioning (Depp et al., 2012; Zarate et al., 2000). Therefore, the present
study investigates whether patients receiving CRT improve with regard to
subjective cognitive symptoms. We expect such an improvement after CRT and
hypothesize that this improvement can also be measured using a
neuropsychological assessment.

The primary objective of the study is to investigate whether CRT reduces
subjective cognitive symptoms.
It is hypothesized that there is a significant improvement in
subjective cognitive symptoms as measured by the Cognitive Failure
Questionnaire (CFQ; Ponds et al., 1998) on the post-test (T1, after CRT)
compared to the pre-test (T0, before CRT).
The secondary objective is to investigate whether this improvement can be
measured using a neuropsychological assessment.
It is hypothesized that cognitive improvement is apparent i.e., higher
scores on neuropsychological assessment are expected after CRT (T1) compared to
before CRT (T0). Whether these kinds of improvements can be measured using a
neuropsychological assessment is debated (Harvey,2012; Wilson, 2003) but we
expect to find significant differences between the two neuropsychological
assessments.

This study is a naturalistic pre-test-post-test design. Patients follow the
regular treatment procedure designed for patients with bipolar disorder who
experience cognitive difficulties. The research will last three years and will
take place within GGz Breburg, with team bipolar West and team bipolar East.
A pre-test-post-test design is chosen because it allows to determine whether
there are indications that CRT may have a positive effect on cognitive
complaints in patients with bipolar disorder. The advantage of such a design is
that burden for patients is considered minimal (i.e., CRT is regular care, the
first, short, neuropsychological assessment serves as an indicator for the
direction/aim of CRT). The disadvantage of this design is that it does not
allow any statements regarding the causality.

CRT is made freely available (Boom, 2010)
(https://www.boompsychologie.nl/productgroep/101-15_Neuropsychologie#downloads).

The CRT is offered individually to a patient. It is applied to a specific
cognitive problem that must be objectified prior to the CRT (conformed in the
protocol, see
https://www.boompsychologie.nl/media/13/protocol_dysexecutief_syndroom.pdf).
This allows a practitioner to tailor treatment to a patient's perceived
cognitive symptom. At the start of the CRT, the problems in daily are examined
together with the patient which he or encounters as a result of the cognitive
symptoms. Treatment consists of three phases; 1) psychoeducation, 2) goal
setting and planning, and 3) implementation. CRT can be aimed at improving
executive functioning, memory problems or problems with time constraints.
Treatment is adapted to the patient's problems. Because of this there is a
variation in the duration of treatment. During CRT, various information
leaflets are used, worksheets and exercises are provided by the treatment
protocol. There is a minimum of 12 sessions and a maximum of 19 sessions. The
intensity and degree of recurrence can be adapted to the patient.

The baseline measurement (pre-test T0) and the intervention are part of the
standard care. The supplement to the study is a post-measurement (post-test) of
no more than one hour. Patients may participate voluntarily and can stop the
study at any time, without giving any reason. The reason for withdrawal from
the CRT is asked, but it is explicitly stated that patients are not required to
provide the reason.
Participation will take place with a signed informed consent for the
pseudo-anonymised use of the collected data. The practitioners are trained in
CRT. With this study, we hope to gain more insight whether CRT may have a
positive effect on the cognitive symptoms of patients with a bipolar disorder.
To the best of our knowledge, this is the first study that explores such a
treatment in this patient group.