• bipolar disorder
• cognitive impairment
• dementia
• elderly

Background: It is widely known that patients with bipolar disorder (BD) have an increased risk of developing dementia, but the factors driving this association are not yet well understood. It is especially interesting to evaluate patients with Older Age Bipolar Disorder (OABD) as it represents one of the main segment of the population at risk for dementia. The International Society for Bipolar Disorders (ISBD) Task Force has introduced the term OABD to replace the previously used "geriatric bipolar disorder. The delineation of OABD has often employed a cut-off age of 60 years. However, prior studies have varied in their chosen thresholds, encompassing ages such as 50, 55, or 65 years. In 2015, the ISBD recommended defining OABD as Bipolar Disorder occurring in individuals aged 50 years or older. This broader age range facilitates studying these patients across their lifespan, considering their elevated rates of comorbidity and premature mortality.

Materials and Methods: From June 2020 to September 2023, participants were recruited from a pool of patients attending the psychogeriatric outpatient clinic at Psychiatry Unit 2, University Hospital of Pisa, Italy. This naturalistic observational study aims to pinpoint clinical indicators that predict the onset of dementia in individuals with bipolar spectrum disorders. Thus, this research seeks to provide fresh insights into intervening on these variables within BD population. The study included patients who met specific inclusion criteria: (1) aged 50 years or older, (2) diagnosed with Bipolar Disorder (Type 1, 2, "Other Specified," or "Unspecified"), and (3) diagnosed with Cyclothymic Disorder based on DSM-5-TR criteria. Exclusion criterions comprised individuals with Parkinson's disease or other parkinsonisms. Among the evaluated subjects, 143 patients met these criteria. Various patient details such as demographic information (age, sex), educational background, marital status, family psychiatric and neurodegenerative history, medical conditions (including Mild Cognitive Impairment based on Peterson criteria), imaging results, and current as well as lifetime psychiatric diagnoses per DSM-5-TR criteria were inputted into a digital database.Information on suicidal attempts, course characteristics, and follow-up assessments was also recorded. To gauge the severity of psychiatric illness, the Clinical Global Impression Severity Scale (CGI-S) was employed at baseline and follow-up visits. Symptoms severity was assessed using the Brief Psychiatric Rating Scale, Extended Version (BPRS), while overall functioning was measured using the Global Assessment of Functioning (GAF). BPRS subscales were determined following the model outlined by Velligan and colleagues. Additionally, the Mini-Mental State Examination (MMSE) was administered as part of our routine clinical practice. The reported variables were retrospectively evaluated by logistic regression and then selected according to Stepwise backward Selection, removing non-significant variables and enhancing its interpretability and predictive power.

Results: Significant differences were observed between patients with and without dementia in the scores of CGI, GAF and BPRS—except for the Depressive Symptoms subscale of the BPRS. In particular, BD2 (OR: 5.45, p = 0.038) and BD-NOS (OR: 6.36, p = 0.031) showed greater significance, demonstrating a consistent and influential relationship with the development of dementia. Finally, a statistically significant correlation with the development of dementia was found also for the age of onset of psychiatric symptoms (OR: 1.03, p = 0.021).

Conclusion: Our study indicated that BD 2 had a stronger association with dementia compared to other types of mood disorders. This supports the notion that BD 2, often characterized by later onset compared to cyclothymic disorder and BD 1, might have a closer connection to dementia onset. Furthermore, the late onset of psychiatric symptoms in our sample (after 40 years old) appears to correlate with dementia, confirming our earlier observations regarding BD 2. Obviously, greater disease severity at assessment more prominently correlates with dementia presence compared to patients without it. Considering the multifaceted nature of dementias and the intricate links between neurodegenerative and mood disorders, exploring new associations between these disorders could facilitate more targeted interventions focused on critical variables affecting cognitive decline. Identifying specific predictors of dementia earlier could lead to earlier diagnosis, significantly improving disease management.