Abstract
Bipolar disorder is associated with an increased risk of dementia with aging. Little is known regarding this association, limiting appropriate diagnosis and management. We aimed to describe the characteristics of bipolar patients with late cognitive impairment for whom the hypothesis of an underlying neurodegenerative disease had been raised. We performed a retrospective multicenter study, recruiting bipolar patients over 50 years old from five French tertiary memory centers who had undergone cerebrospinal fluid (CSF) biomarker assessment for Alzheimer’s disease (AD). Clinical, neuropsychological, and paraclinical characteristics were analyzed and 78 patients were included. The mean age at the onset of cognitive impairment was 62.4 years (±9.2). The mean MMSE score was 22.8 (±4.5), the mean FAB was 11.7 (±3.9), and the mean FCRST was 15.8 (±7.4)/36.8 (±9.7) (free/total recall). A total of 48.6% of the patients displayed cognitive fluctuations, and 38.2% showed cognitive improvement during follow-ups; and 56.3% of the patients showed Parkinsonism, of which 12.7% had never received antipsychotics. Among patients who underwent DAT-scans, 35.3% displayed dopaminergic denervation; 10.3% of patients had CSF AD biological signature (“A+ T+” profile), while 56.4% had other abnormal CSF profiles. Thus, clinical presentation was dominated by executive dysfunction, episodic memory impairment, fluctuating cognition, and a high frequency of Parkinsonism. Specifically, high frequency of delusional episodes suggests limited tolerance of psychotropic drugs. Most patients had abnormal CSF biomarker profiles, but only a minority displayed AD’s specific biomarker signature. Therefore, while our results unveil shared common neurocognitive features in bipolar patients with cognitive impairment of suspected neurodegenerative origin they suggest a participation of various underlying pathologies rather than a common degenerative mechanism in the pathophysiology of this condition.
Highlights
Patients with bipolar disorder (BD) display neuropsychological deficits in their attentional capacities, executive functions, and episodic verbal memory
We described the characteristics of a large cohort of patients with BD with late cognitive impairment of suspected neurodegenerative origin (CI-SNO)
We showed that patients with cognitive impairment and a cerebrospinal fluid (CSF) A−, T+ profile mainly received a diagnosis of frontotemporal dementia (FTD) [35]
Summary
Patients with bipolar disorder (BD) display neuropsychological deficits in their attentional capacities, executive functions, and episodic verbal memory. These deficits may be detected as early as the first episode and persist throughout life, including periods of euthymia [1]. They are at increased risk of dementia while aging [2], with an odds ratio ranging from 2.96 to 7.52 compared to the general population [3,4]. A neurodegenerative process is most commonly suspected as some studies have shown the existence of accelerated brain aging in BD [5,6]. The main alternative hypothesis relies on neuroprogression, a concept postulating that the repetition of mood episodes would cause irreversible neuronal changes that can lead to increased relapse frequency, decreased response to treatment, and cognitive decline [11]
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