Bipolar Disorder and Manic-Like Symptoms in Alzheimer’s, Vascular and Frontotemporal Dementia: A Systematic Review

Abstract

Background: An increased risk of manic episodes has been reported in patients with neurodegenerative disorders, but the clinical features of bipolar disorder (BD) in different subtypes of dementia have not been thoroughly investigated. Objectives: The main aim of this study is systematically review clinical and therapeutic evidence about manic syndromes in patients with Alzheimer’s disease (AD), vascular dementia (VD), and frontotemporal dementia (FTD). Since manic-mixed episodes have been associated with negative outcomes in patients with dementia and often require medical intervention, we also critically summarized selected studies with relevance for the treatment of mania in patients with cognitive decline. Methods: A systematic review of the literature was conducted according to PRISMA guidelines. PubMed, Scopus and Web of Science databases were searched up to February 2022. Sixty-one articles on patients with AD, VaD or FTD and BD or (hypo)mania have been included. Results: Manic symptoms seem to be associated with disease progression in AD, have a greatly variable temporal relationship with cognitive decline in VaD, and frequently coincides with or precedes cognitive impairment in FTD. Overall, mood stabilizers and electroconvulsive therapy may be the most effective treatments, while the benefits of short-term treatment with antipsychotic agents must be balanced with the associated risks. Importantly, low-dose lithium salts may exert a neuroprotective activity in patients with AD. Conclusion: Prevalence, clinical features and treatment response to pharmacotherapy of manic syndromes in patients with dementia may be differentially affected by the nature of the underlying neurodegenerative conditions.

Comorbidity of undiagnosed mood symptoms with dementia risk in multi-regional multi-ethnic adults: evidence from epidemiological findings and plasma metabolites

“…The results showed that prevalence of manic symptoms in the Asian sample (12.9%) was higher than in the UKB sample (2.6%). Our findings were comparable with previous studies (Elefante et al , 2023 ; Smith et al , 2013 ; Xu et al , 2022 ; Zhang et al , 2024c ). The difference between the Asian sample and the UKB sample could possibly be due to the older mean age in the Asian sample, as compared to the UKB sample (70.5 vs 57.2 years of age).…”

“…Our results were consistent with previous findings showing that bipolar disorder was associated with a higher risk of dementia than unipolar depressive disorder across studies conducted around the world (Liou et al , 2023 ; Liu et al , 2024 ; Stevenson-Hoare et al , 2024 ). In addition, depressive or manic symptoms were associated with higher risk of dementia compared to euthymic individual, which was in line with previous studies (Elefante et al , 2023 ; Kaup et al , 2016 ; Koga et al , 2022 ). The results further validate that undiagnosed mood symptoms comorbidity could be an independent risk factor for incident dementia.…”

Comorbidity of undiagnosed mood symptoms with dementia risk in multi-regional multi-ethnic adults: evidence from epidemiological findings and plasma metabolites

“…The results showed that prevalence of manic symptoms in the Asian sample (12.9%) was higher than in the UKB sample (2.6%). Our findings were comparable with previous studies (Elefante et al , 2023 ; Smith et al , 2013 ; Xu et al , 2022 ; Zhang et al , 2024c ). The difference between the Asian sample and the UKB sample could possibly be due to the older mean age in the Asian sample, as compared to the UKB sample (70.5 vs 57.2 years of age).…”

“…Our results were consistent with previous findings showing that bipolar disorder was associated with a higher risk of dementia than unipolar depressive disorder across studies conducted around the world (Liou et al , 2023 ; Liu et al , 2024 ; Stevenson-Hoare et al , 2024 ). In addition, depressive or manic symptoms were associated with higher risk of dementia compared to euthymic individual, which was in line with previous studies (Elefante et al , 2023 ; Kaup et al , 2016 ; Koga et al , 2022 ). The results further validate that undiagnosed mood symptoms comorbidity could be an independent risk factor for incident dementia.…”

Type 2 diabetes mellitus is associated with manic morbidity in elderly patients with mood disorders

“…the literature (Wijeratne and Malhi, 2007;Elefante et al, 2022b). In our sample, vascular encephalopathy, as well as neurocognitive disorders, was significantly more frequently documented in patients with T2DM than in the others and possibly contributed to the increased occurrence of manic episodes in these patients.…”

Adverse events of Alzheimer's disease patients treated with memantine-based therapies: A disproportionality analysis of the FAERS database based on the MY FAERS platform

“…These findings are partially consistent with existing literature, which suggests that SGAs may exacerbate manic-like symptoms in patients with AD, particularly when co-administered with other central nervous system agents such as memantine. 31 Moreover, prior studies have reported that the sedative and extrapyramidal effects of SGAs may contribute to an increased risk of falls and fractures in older adults. 32 From a mechanistic perspective, it is conceivable that memantine, through modulation of glutamatergic signaling, may interact with the central nervous system effects of SGAs and potentially intensify inhibitory or neuropsychiatric responses.…”

Comorbidity of undiagnosed mood symptoms with dementia risk in multi-regional multi-ethnic adults: evidence from epidemiological findings and plasma metabolites

“…The results showed that prevalence of manic symptoms in the Asian sample (12.9%) was higher than in the UKB sample (2.6%). Our findings were comparable with previous studies (Elefante et al , 2023 ; Smith et al , 2013 ; Xu et al , 2022 ; Zhang et al , 2024c ). The difference between the Asian sample and the UKB sample could possibly be due to the older mean age in the Asian sample, as compared to the UKB sample (70.5 vs 57.2 years of age).…”

“…Our results were consistent with previous findings showing that bipolar disorder was associated with a higher risk of dementia than unipolar depressive disorder across studies conducted around the world (Liou et al , 2023 ; Liu et al , 2024 ; Stevenson-Hoare et al , 2024 ). In addition, depressive or manic symptoms were associated with higher risk of dementia compared to euthymic individual, which was in line with previous studies (Elefante et al , 2023 ; Kaup et al , 2016 ; Koga et al , 2022 ). The results further validate that undiagnosed mood symptoms comorbidity could be an independent risk factor for incident dementia.…”

Type 2 diabetes mellitus is associated with manic morbidity in elderly patients with mood disorders

“…the literature (Wijeratne and Malhi, 2007;Elefante et al, 2022b). In our sample, vascular encephalopathy, as well as neurocognitive disorders, was significantly more frequently documented in patients with T2DM than in the others and possibly contributed to the increased occurrence of manic episodes in these patients.…”

Adverse events of Alzheimer's disease patients treated with memantine-based therapies: A disproportionality analysis of the FAERS database based on the MY FAERS platform

“…These findings are partially consistent with existing literature, which suggests that SGAs may exacerbate manic-like symptoms in patients with AD, particularly when co-administered with other central nervous system agents such as memantine. 31 Moreover, prior studies have reported that the sedative and extrapyramidal effects of SGAs may contribute to an increased risk of falls and fractures in older adults. 32 From a mechanistic perspective, it is conceivable that memantine, through modulation of glutamatergic signaling, may interact with the central nervous system effects of SGAs and potentially intensify inhibitory or neuropsychiatric responses.…”

Comorbidity of undiagnosed mood symptoms with dementia risk in multi-regional multi-ethnic adults: evidence from epidemiological findings and plasma metabolites

“…The results showed that prevalence of manic symptoms in the Asian sample (12.9%) was higher than in the UKB sample (2.6%). Our findings were comparable with previous studies (Elefante et al , 2023 ; Smith et al , 2013 ; Xu et al , 2022 ; Zhang et al , 2024c ). The difference between the Asian sample and the UKB sample could possibly be due to the older mean age in the Asian sample, as compared to the UKB sample (70.5 vs 57.2 years of age).…”

“…Our results were consistent with previous findings showing that bipolar disorder was associated with a higher risk of dementia than unipolar depressive disorder across studies conducted around the world (Liou et al , 2023 ; Liu et al , 2024 ; Stevenson-Hoare et al , 2024 ). In addition, depressive or manic symptoms were associated with higher risk of dementia compared to euthymic individual, which was in line with previous studies (Elefante et al , 2023 ; Kaup et al , 2016 ; Koga et al , 2022 ). The results further validate that undiagnosed mood symptoms comorbidity could be an independent risk factor for incident dementia.…”

Type 2 diabetes mellitus is associated with manic morbidity in elderly patients with mood disorders

“…the literature (Wijeratne and Malhi, 2007;Elefante et al, 2022b). In our sample, vascular encephalopathy, as well as neurocognitive disorders, was significantly more frequently documented in patients with T2DM than in the others and possibly contributed to the increased occurrence of manic episodes in these patients.…”

Adverse events of Alzheimer's disease patients treated with memantine-based therapies: A disproportionality analysis of the FAERS database based on the MY FAERS platform

“…These findings are partially consistent with existing literature, which suggests that SGAs may exacerbate manic-like symptoms in patients with AD, particularly when co-administered with other central nervous system agents such as memantine. 31 Moreover, prior studies have reported that the sedative and extrapyramidal effects of SGAs may contribute to an increased risk of falls and fractures in older adults. 32 From a mechanistic perspective, it is conceivable that memantine, through modulation of glutamatergic signaling, may interact with the central nervous system effects of SGAs and potentially intensify inhibitory or neuropsychiatric responses.…”