Investigating neuropathological correlates of hyperactive and psychotic symptoms in dementia: a systematic review
IntroductionBehavioral and Psychological Symptoms of Dementia (BPSD) are common neuropsychiatric manifestations that complicate the clinical course of dementia and impact caregiving. Among these, the Hyperactivity–Impulsivity–Irritiability–Disinhibition–Aggression–Agitation (HIDA) and Psychosis (P)...
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Frontiers Media S.A.
2025-01-01
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| author | Giulia Negro Giulia Negro Michele Rossi Camillo Imbimbo Alberto Gatti Andrea Magi Andrea Magi Ildebrando Marco Appollonio Ildebrando Marco Appollonio Alfredo Costa Alfredo Costa Tino Emanuele Poloni Tino Emanuele Poloni |
| author_facet | Giulia Negro Giulia Negro Michele Rossi Camillo Imbimbo Alberto Gatti Andrea Magi Andrea Magi Ildebrando Marco Appollonio Ildebrando Marco Appollonio Alfredo Costa Alfredo Costa Tino Emanuele Poloni Tino Emanuele Poloni |
| author_sort | Giulia Negro |
| collection | DOAJ |
| description | IntroductionBehavioral and Psychological Symptoms of Dementia (BPSD) are common neuropsychiatric manifestations that complicate the clinical course of dementia and impact caregiving. Among these, the Hyperactivity–Impulsivity–Irritiability–Disinhibition–Aggression–Agitation (HIDA) and Psychosis (P) domains are particularly challenging to manage. Despite their prevalence, their underlying mechanisms and neuropathological correlates, remain poorly understood. This systematic review aims to elucidate the neuropathological basis of the HIDA and psychosis domains, exploring whether distinct proteinopathies and neural circuit dysfunctions are associated with these symptoms.MethodsThe review follows PRISMA guidelines, with a systematic search conducted across MEDLINE, CENTRAL, and EMBASE databases. Inclusion criteria involved studies exploring the neuropathology of the HIDA and psychosis domains in individuals with dementia. Records were screened using PICO software, and data quality was assessed using the Newcastle-Ottawa Scale (NOS) and CARE guidelines. A narrative synthesis was conducted due to heterogeneity in the data.ResultsFrom 846 records identified, 37 studies met inclusion criteria. Of the 18,823 cases analyzed, the most common diagnoses were Alzheimer's Disease (83.44%), Dementia with Lewy Bodies (5.37%), and Frontotemporal Dementia (13.40%). HIDA-P symptoms were distributed across all clinical diagnoses, with agitation (14.00%), delusions (11.60%), disinhibition (7.61%), and hallucinations (6.83%) being the most frequently reported behaviors. The primary neuropathological diagnosis was Alzheimer's Disease Neuropathologic Change (ADNC), present predominantly in intermediate to severe forms. The neuropathological analysis revealed the co-occurrence of multiple proteinopathies, particularly TAUopathy, TDP-43 pathology, and Lewy-related pathology (LRP), with the latter, in association with ADNC, reported in 15 studies.DiscussionHIDA-P symptoms were linked with overlapping involvement of different neural circuits, particularly the amygdala and the broader limbic system. Evidence suggests that TAUopathy and multiple proteinopathies in key brain regions, such as amygdala, are central to the development of these symptoms. In contrast, the contribution of beta-amyloid and vascular damage appears marginal in the genesis of HIDA and psychotic symptoms. No behavioral symptom is pathognomonic of a specific proteinopathy; rather, the topography and severity of lesions plays a more decisive role than their single molecular composition.Systematic review registrationINPLASY2024100082. |
| format | Article |
| id | doaj-art-9783a7a37f114859a3e722264ef45fb6 |
| institution | Kabale University |
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| language | English |
| publishDate | 2025-01-01 |
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| series | Frontiers in Dementia |
| spelling | doaj-art-9783a7a37f114859a3e722264ef45fb62025-01-29T06:45:55ZengFrontiers Media S.A.Frontiers in Dementia2813-39192025-01-01410.3389/frdem.2025.15136441513644Investigating neuropathological correlates of hyperactive and psychotic symptoms in dementia: a systematic reviewGiulia Negro0Giulia Negro1Michele Rossi2Camillo Imbimbo3Alberto Gatti4Andrea Magi5Andrea Magi6Ildebrando Marco Appollonio7Ildebrando Marco Appollonio8Alfredo Costa9Alfredo Costa10Tino Emanuele Poloni11Tino Emanuele Poloni12Neurology Department, Fondazione IRCCS San Gerardo dei Tintori, San Gerardo Hospital, Monza, ItalySchool of Medicine and Surgery and Milan Centre for Neuroscience (NeuroMI), University of Milano-Bicocca, Milan, ItalyUnit of Biostatistics, Golgi-Cenci Foundation, Abbiategrasso, Milan, ItalyDepartment of Brain and Behavioral Sciences, University of Pavia, Pavia, ItalyDepartment of Brain and Behavioral Sciences, University of Pavia, Pavia, ItalyNeurology Department, Fondazione IRCCS San Gerardo dei Tintori, San Gerardo Hospital, Monza, ItalySchool of Medicine and Surgery and Milan Centre for Neuroscience (NeuroMI), University of Milano-Bicocca, Milan, ItalyNeurology Department, Fondazione IRCCS San Gerardo dei Tintori, San Gerardo Hospital, Monza, ItalySchool of Medicine and Surgery and Milan Centre for Neuroscience (NeuroMI), University of Milano-Bicocca, Milan, ItalyDepartment of Brain and Behavioral Sciences, University of Pavia, Pavia, ItalyUnit of Behavioral Neurology and Center for Cognitive Disorders and Dementia (CDCD), IRCCS Mondino Foundation, Pavia, ItalyDepartment of Neurology and Neuropathology, Golgi-Cenci Foundation, Abbiategrasso, Milan, ItalyDepartment of Rehabilitation, ASP Golgi-Redaelli, Abbiategrasso, Milan, ItalyIntroductionBehavioral and Psychological Symptoms of Dementia (BPSD) are common neuropsychiatric manifestations that complicate the clinical course of dementia and impact caregiving. Among these, the Hyperactivity–Impulsivity–Irritiability–Disinhibition–Aggression–Agitation (HIDA) and Psychosis (P) domains are particularly challenging to manage. Despite their prevalence, their underlying mechanisms and neuropathological correlates, remain poorly understood. This systematic review aims to elucidate the neuropathological basis of the HIDA and psychosis domains, exploring whether distinct proteinopathies and neural circuit dysfunctions are associated with these symptoms.MethodsThe review follows PRISMA guidelines, with a systematic search conducted across MEDLINE, CENTRAL, and EMBASE databases. Inclusion criteria involved studies exploring the neuropathology of the HIDA and psychosis domains in individuals with dementia. Records were screened using PICO software, and data quality was assessed using the Newcastle-Ottawa Scale (NOS) and CARE guidelines. A narrative synthesis was conducted due to heterogeneity in the data.ResultsFrom 846 records identified, 37 studies met inclusion criteria. Of the 18,823 cases analyzed, the most common diagnoses were Alzheimer's Disease (83.44%), Dementia with Lewy Bodies (5.37%), and Frontotemporal Dementia (13.40%). HIDA-P symptoms were distributed across all clinical diagnoses, with agitation (14.00%), delusions (11.60%), disinhibition (7.61%), and hallucinations (6.83%) being the most frequently reported behaviors. The primary neuropathological diagnosis was Alzheimer's Disease Neuropathologic Change (ADNC), present predominantly in intermediate to severe forms. The neuropathological analysis revealed the co-occurrence of multiple proteinopathies, particularly TAUopathy, TDP-43 pathology, and Lewy-related pathology (LRP), with the latter, in association with ADNC, reported in 15 studies.DiscussionHIDA-P symptoms were linked with overlapping involvement of different neural circuits, particularly the amygdala and the broader limbic system. Evidence suggests that TAUopathy and multiple proteinopathies in key brain regions, such as amygdala, are central to the development of these symptoms. In contrast, the contribution of beta-amyloid and vascular damage appears marginal in the genesis of HIDA and psychotic symptoms. No behavioral symptom is pathognomonic of a specific proteinopathy; rather, the topography and severity of lesions plays a more decisive role than their single molecular composition.Systematic review registrationINPLASY2024100082.https://www.frontiersin.org/articles/10.3389/frdem.2025.1513644/fullneuropathologyBPSDneuropsychiatric symptomspsychosisdementiaAlzheimer |
| spellingShingle | Giulia Negro Giulia Negro Michele Rossi Camillo Imbimbo Alberto Gatti Andrea Magi Andrea Magi Ildebrando Marco Appollonio Ildebrando Marco Appollonio Alfredo Costa Alfredo Costa Tino Emanuele Poloni Tino Emanuele Poloni Investigating neuropathological correlates of hyperactive and psychotic symptoms in dementia: a systematic review Frontiers in Dementia neuropathology BPSD neuropsychiatric symptoms psychosis dementia Alzheimer |
| title | Investigating neuropathological correlates of hyperactive and psychotic symptoms in dementia: a systematic review |
| title_full | Investigating neuropathological correlates of hyperactive and psychotic symptoms in dementia: a systematic review |
| title_fullStr | Investigating neuropathological correlates of hyperactive and psychotic symptoms in dementia: a systematic review |
| title_full_unstemmed | Investigating neuropathological correlates of hyperactive and psychotic symptoms in dementia: a systematic review |
| title_short | Investigating neuropathological correlates of hyperactive and psychotic symptoms in dementia: a systematic review |
| title_sort | investigating neuropathological correlates of hyperactive and psychotic symptoms in dementia a systematic review |
| topic | neuropathology BPSD neuropsychiatric symptoms psychosis dementia Alzheimer |
| url | https://www.frontiersin.org/articles/10.3389/frdem.2025.1513644/full |
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