Dementia And Bipolar.
“WE CAN’T HELP EVERYONE, BUT EVERYONE CAN HELP SOMEONE.” – RONALD REAGAN.
A 67-year-old female patient was referred to tertiary care hospital for a second opinion regarding a severe treatment-resistant depression. She was first referred to the department of psychiatry. Because she also suffered from severe cognitive problems, she was subsequently referred to the department of neurology. After extensive neurologic evaluation she was referred back to the department of psychiatry.
Dementia is a syndrome of cognitive deficits that is generally characterised by impairment in short- and long-term memory, and is often associated with impairment in abstract thinking or judgment, other disturbances of higher cortical function such as aphasia or apraxia, or personality change. The cognitive deficits are severe enough to interfere significantly with work or usual social activities or relationships with others, and are not only present during a delirium.
Her medical history included a type 1 bipolar disorder since the age of eighteen years, with frequent manic and depressive episodes and frequent admissions. Between manic and depressive episodes, she was functioning well and worked as a social worker. she had been stable on a combination of lithium and carbamazepine for eighteen years.
Among the most prevalent diseases that can cause reversible dementia are affective disorders. Affective disorders include major depressive disorder, bipolar disorder, dysthymic disorder and cyclothymic disorder.It has been estimated that in approximately 1% of the cases, dementia is caused by a major depressive disorder. Probably, this percentage is higher in persons aged <70 years. A study found that 3% of the patients aged <70 had dementia due to mental illness such as schizoaffective disorder and major depressive disorder. It has also been suggested that in patients with dementia due to a major depressive disorder, the dementia may be completely reversible in 30% of the patients.
In May 2010, the current disease episode started with manic symptoms. In that period, carbamazepine was discontinued because of a confirmed allergic reaction. It is possible that this event caused the manic episode. In December 2010, this was followed by severe depressive symptoms and psychosis. She was treated with different combinations of antipsychotics (quetiapine, risperidone, aripiprazole), mood stabilizers (lamotrigine, topiramate, valproic acid) and antidepressants (clomipramine), without any effect on symptoms. Lithium was discontinued after an emergency admission for lithium intoxication. In November 2011, the patient was treated with electroconvulsive therapy (ECT), also without improvement of the symptoms. In the last months before transfer to hospital, her husband noticed progressive memory problems, especially in the short-time memory.
However, up till now, many questions remain unanswered. For example, little is known about the severity of cognitive deficits in patients with reversible dementia due to a depressive disorder, or whether the severity of these deficits determine the reversibility. Also, it is still unclear if reversibility of the cognitive deficits is dependent on the type of affective disorder. Although some studies report improvement of cognitive deficits after successful treatment of patients with a major depressive disorder with psychotic features, other studies report persisting cognitive deficits in patients with a bipolar disorder.
In February 2012, the Mini-Mental State Examination (MMSE) score was 12. Neuropsychological testing at that time was impossible because she was very disorientated and not cooperative. In October 2012, the patient was admitted to tertiary hospital to further evaluate her depressive episode and cognitive problems. As common antidepressant treatments seemed to be ineffective and memory impairment progressed, we considered an underlying neurodegenerative disease as the main cause of her complaints.
Dementia is most commonly caused by a neurodegenerative disease, such as Alzheimer’s disease, vascular dementia or Parkinson’s disease. Therefore, dementia is generally considered an irreversible process of cognitive decline.
During her stay, it was observed that she clearly had memory problems and could not find her way on the ward. She also had great difficulty in executive functioning tasks such as cooking and there were signs of apraxia. She was not able to dress and wash herself. In addition, she suffered from hallucinations and delusional ideas which were nihilistic in nature.
The differential diagnosis included neurodegenerative disease or cognitive impairment as the result of severe depression with psychotic features. Because her situation was very severe we decided to perform additional diagnostic investigations for neurodegenerative disease such as neuroimaging and CSF analysis. However, the results of the magnetic resonance imaging (MRI) scan and 18 F-fluoro-deoxy-glucose positron emission tomography (FDG-PET) scan of the brain did not match classic patterns of known neurodegenerative causes. In combination with the negative results of the cerebrospinal fluid (CSF) analysis, it seemed unlikely that her cognitive impairment was caused by a neurodegenerative disease.We decided to treat the patient for a severe depressive episode with psychotic features.
The diagnosis of dementia has great implications for the patients and their relatives. Unfortunately, the diagnosis is often difficult to confirm in elderly patients with a history of affective disorder. Especially in these patients, there is a considerable risk of missing a potentially reversible condition such as a major depressive or bipolar disorder.
After careful evaluation of prior medication use, we started with nortriptylin with monitoring of the serum levels. In the following months, we saw a slow but significant improvement of her mood disorder and cognitive functioning.
In clinical practice, doctors often see elderly patients with depressive symptoms and cognitive impairment. Differentiating between a major depression with cognitive symptoms and early dementia is a great challenge. Depression or feelings of sadness can be the first symptom of a neurodegenerative disease, whereas memory complaints and other cognitive impairments can be part of a depressive disorder.
Improvement of cognitive impairment following antidepressive treatment has been reported in the literature. However, the effects are small and only measured as change in MMSE score.
Our patient had more severe cognitive impairment than any other patient described in the literature. Usually, such severe symptoms are caused by a neurodegenerative disease. However, despite extensive evaluation, we could not find any other evidence that supported the diagnosis of a neurodegenerative disease. The patient improved solely on a low dose of nortriptyline in addition to the restart of lithium and discontinuation of antipsychotic medication which is highly unlikely in case of a neurodegenerative disease. Although she did not completely improve to her premorbid level of functioning, improvement was striking and of great value for the patient and her family.
We assume that the severe cognitive symptoms at admission, were a combination of major depressive disorder with psychotic features, and the adverse effects of medication (mainly antipsychotics). The remaining cognitive deficits could be explained in the light of her long existent bipolar disorder with frequent manic and depressive episodes in the past and the long duration of her last episode.
Finally, in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) that was recently published by the American Psychiatric Association (APA), the term dementia was replaced with the term major neurocognitive disorder. We think that our case study illustrates the advantages of this new term. Although physicians and patients may be accustomed to the term dementia, dementia is generally associated with neurodegenerative and cerebrovascular diseases that have a progressive course and cannot be reversed or cured. As a consequence, the term reversible dementia easily leads to confusion. Furthermore, a considerable number of persons aged <70 years are diagnosed with dementia that is caused by nondegenerative, nonvascular diseases. Therefore, in our opinion, major neurocognitive disorder is the preferred term used when referring to persons aged <70 years with severe cognitive deficits that are caused by nondegenerative, nonvascular diseases and may be amenable to curative treatment.
“ONE OF THE WORST THINGS THAT CAN HAPPEN TO A PERSON IS TO BE FORGOTTEN BY SOMEONE THEY WILL NEVER FORGET.”