INS NYC 2024 Program

Poster	Poster Session 06 Program Schedule 02/15/2024 04:00 pm - 05:15 pm Room: Shubert Complex (Posters 1-60) Poster Session 06: Aging \| MCI \| Neurodegenerative Disease - PART 2 Final Abstract #54 Understanding the Relationships between Alzheimer’s Disease Pathology, Brain Function, and Later-Life Neuropsychiatric Symptoms Alexandru Iordan, University of Michigan, Ann Arbor, United States Robert Ploutz-Snyder, University of Michigan, Ann Arbor, United States Annalise Rahman-Filipiak, University of Michigan, Ann Arbor, United States Robert Koeppe, University of Michigan, Ann Arbor, United States Bruno Giordani, University of Michigan, Ann Arbor, United States Roger Albin, University of Michigan, Ann Arbor, United States Benjamin Hampstead, University of Michigan, Ann Arbor, United States Category: Dementia (Alzheimer's Disease) Keyword 1: neuropsychological assessment Keyword 2: emotional processes Keyword 3: neuroimaging: functional Objective: Later-life neuropsychiatric symptoms have been associated with a greater risk of dementia but are all too often viewed and treated as independent of Alzheimer’s disease (AD) and related dementias. This traditional approach overlooks the possibility that these neuropsychiatric symptoms emerge as pathology accumulates in brain regions that differ from those affected by the more common “memory first” phenotype. A recently developed mild behavioral impairment (MBI) diagnostic framework standardizes the assessment of neuropsychiatric symptoms in older adults during the pre-dementia phase(s). However, the links between MBI and AD pathology are unclear. Here, we asked whether MBI arises from a network-level impact of AD pathology on neural circuitry primarily implicated in the processing and integration of emotional experience - i.e., the salience and default-mode brain networks. Participants and Methods: We analyzed data from 95 individuals (46 male) enrolled in the “Stimulation to Improve Memory” study (R01AG058724; PI Hampstead) who have completed neuropsychological, structural and functional MRI, and amyloid and tau positron emission tomography (PET) assessments. We used PET-derived biomarkers status to separate participants into three categories: (1) AD biomarker negative, (2) amyloid positive and tau negative, and (3) amyloid and tau positive. To assess network-level function, we calculated brain network segregation during resting-state functional MRI. We focused on three outcomes, specifically the overall segregation of the salience and default-mode networks from the other association networks, as well as from each-other. Multivariate regression assessed the effect of AD biomarker status on network segregation measures. Path analysis using negative binomial regression assessed the effect of AD biomarker status on MBI and the mediation of this effect through brain function. We accounted for sex, age, education, and cognitive performance in our analyses. Results: The effect of tau-PET positivity on the three multivariate brain outcomes was significant for the salience network (p=0.037) and borderline for the default-mode network (p=0.063). Our path analysis evaluating the mediation effect of AD biomarker status on MBI through brain function revealed a significant mediation effect through the overall segregation of salience network (p=0.017) and the segregation between the salience and default-mode networks (p=0.018), and no direct influence of AD biomarker status on MBI. Conclusions: Our findings suggest a potential neural basis for neuropsychiatric symptoms in the context of AD pathology. This involves the salience and default-mode networks which are pivotal for the processing and integration of emotional experience, respectively. Importantly, these relationships were observed even after accounting for effects of cognitive impairment. Future directions include indexing amyloid and tau burden at the nodal level to provide a more fine-grained understanding of network-level interactions. Recognizing MBI as a potential early sign of underlying neural dysfunction can lead to earlier and more targeted interventions in individuals at risk for AD and related dementias.

Poster

02/15/2024
04:00 pm - 05:15 pm
Room: Shubert Complex (Posters 1-60)

Poster Session 06: Aging | MCI | Neurodegenerative Disease - PART 2

Final Abstract #54

Understanding the Relationships between Alzheimer’s Disease Pathology, Brain Function, and Later-Life Neuropsychiatric Symptoms

Alexandru Iordan, University of Michigan, Ann Arbor, United States
Robert Ploutz-Snyder, University of Michigan, Ann Arbor, United States
Annalise Rahman-Filipiak, University of Michigan, Ann Arbor, United States
Robert Koeppe, University of Michigan, Ann Arbor, United States
Bruno Giordani, University of Michigan, Ann Arbor, United States
Roger Albin, University of Michigan, Ann Arbor, United States
Benjamin Hampstead, University of Michigan, Ann Arbor, United States

Category: Dementia (Alzheimer's Disease)

Keyword 1: neuropsychological assessment
Keyword 2: emotional processes
Keyword 3: neuroimaging: functional

Objective:

Later-life neuropsychiatric symptoms have been associated with a greater risk of dementia but are all too often viewed and treated as independent of Alzheimer’s disease (AD) and related dementias. This traditional approach overlooks the possibility that these neuropsychiatric symptoms emerge as pathology accumulates in brain regions that differ from those affected by the more common “memory first” phenotype. A recently developed mild behavioral impairment (MBI) diagnostic framework standardizes the assessment of neuropsychiatric symptoms in older adults during the pre-dementia phase(s). However, the links between MBI and AD pathology are unclear. Here, we asked whether MBI arises from a network-level impact of AD pathology on neural circuitry primarily implicated in the processing and integration of emotional experience - i.e., the salience and default-mode brain networks.

Participants and Methods:

We analyzed data from 95 individuals (46 male) enrolled in the “Stimulation to Improve Memory” study (R01AG058724; PI Hampstead) who have completed neuropsychological, structural and functional MRI, and amyloid and tau positron emission tomography (PET) assessments. We used PET-derived biomarkers status to separate participants into three categories: (1) AD biomarker negative, (2) amyloid positive and tau negative, and (3) amyloid and tau positive. To assess network-level function, we calculated brain network segregation during resting-state functional MRI. We focused on three outcomes, specifically the overall segregation of the salience and default-mode networks from the other association networks, as well as from each-other. Multivariate regression assessed the effect of AD biomarker status on network segregation measures. Path analysis using negative binomial regression assessed the effect of AD biomarker status on MBI and the mediation of this effect through brain function. We accounted for sex, age, education, and cognitive performance in our analyses.

Results:

The effect of tau-PET positivity on the three multivariate brain outcomes was significant for the salience network (p=0.037) and borderline for the default-mode network (p=0.063). Our path analysis evaluating the mediation effect of AD biomarker status on MBI through brain function revealed a significant mediation effect through the overall segregation of salience network (p=0.017) and the segregation between the salience and default-mode networks (p=0.018), and no direct influence of AD biomarker status on MBI.

Conclusions:

Our findings suggest a potential neural basis for neuropsychiatric symptoms in the context of AD pathology. This involves the salience and default-mode networks which are pivotal for the processing and integration of emotional experience, respectively. Importantly, these relationships were observed even after accounting for effects of cognitive impairment. Future directions include indexing amyloid and tau burden at the nodal level to provide a more fine-grained understanding of network-level interactions. Recognizing MBI as a potential early sign of underlying neural dysfunction can lead to earlier and more targeted interventions in individuals at risk for AD and related dementias.