INS NYC 2024 Program

Poster	Poster Session 02 Program Schedule 02/15/2024 08:00 am - 09:15 am Room: Shubert Complex (Posters 1-60) Poster Session 02: Aging \| MCI \| Neurodegenerative Disease - PART 1 Final Abstract #29 Associations of Objectively-Defined Subtle Cognitive Decline and CSF GAP-43: Impact of GAP-43 on Functional Trajectories Amanda Gonzalez, Department of Psychiatry, University of California San Diego, La Jolla, United States Lauren Edwards, SDSU/UCSD Joint Doctoral Program in Clinical Psychology, San Diego, United States Kelsey Thomas, Research Service, VA San Diego Healthcare System, San Diego, United States Maria Bordyug, Department of Psychiatry, University of California San Diego, La Jolla, United States Einat Brenner, Department of Psychiatry, University of California San Diego, La Jolla, United States Uriel Urias, Department of Psychology, San Diego State University, San Diego, United States Katherine Bangen, Department of Psychiatry, University of California San Diego, La Jolla, United States Category: Dementia (Alzheimer's Disease) Keyword 1: activities of daily living Keyword 2: cognitive course Keyword 3: aging disorders Objective: Objectively-defined subtle cognitive decline (Obj-SCD) is an emerging classification that may identify individuals at risk for future decline and progression to Alzheimer’s disease (AD) prior to a diagnosis of mild cognitive impairment (MCI). Synaptic loss and neurodegeneration are part of the AD pathophysiologic process and may relate to cognition more closely than amyloid-β (Aβ) plaques and neurofibrillary tangles (NFT). Growth-associated protein 43 (GAP-43), a CSF marker of synaptic dysfunction, has been shown to relate to increased risk of converting to dementia although it is unclear whether GAP-43 alterations may be detected in pre-MCI stages. Therefore, in the present study we examined CSF GAP-43 levels among individuals with Obj-SCD cross-sectionally and also examined whether baseline GAP-43 predicts future functional decline. Participants and Methods: Participants included older adults from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) with CSF GAP-43 data available. Participants were divided into 6 groups based on cognitive status (cognitively unimpaired (CU), Obj-SCD, or MCI) and whether they are Aβ negative or positive (+ or -) based on positron emission tomography (PET). Baseline measurements included a total of 653 participants: CU- (n = 171), SCD- (n = 74), MCI- (n = 98), CU+ (n = 95), SCD+ (n = 56), and MCI+ (n = 159). Analysis of variance (ANOVA) compared groups on baseline CSF GAP-43 levels adjusting for age and sex. Linear mixed effects models, adjusting for age, sex, and education, examined the 4-year rate of change in functional abilities (measured with the Functional Activities Questionnaire) by group as well as the extent to which baseline GAP-43 moderated this relationship. Results: ANOVA models showed that the CU- group had lower baseline GAP-43 than all biomarker positive groups. Baseline GAP-43 values did not differ between the CU- group and the other Aβ- groups. Mixed models showed a significant three-way interaction of GAP-43 x group x time such that higher GAP-43 at baseline predicted a steeper rate of decline for the MCI+ and Obj-SCD+ groups, compared to the CU- group. Conclusions: Results extend prior work investigating biomarker associations in Obj-SCD to GAP-43, and show that high baseline CSF GAP-43 is associated with a faster rate of functional decline in Aβ+ individuals who are classified as Obj-SCD or MCI. Importantly, our findings further demonstrate that CSF GAP-43 is associated with early and subtle cognitive changes detectable before onset of MCI.

Poster

02/15/2024
08:00 am - 09:15 am
Room: Shubert Complex (Posters 1-60)

Poster Session 02: Aging | MCI | Neurodegenerative Disease - PART 1

Final Abstract #29

Associations of Objectively-Defined Subtle Cognitive Decline and CSF GAP-43: Impact of GAP-43 on Functional Trajectories

Amanda Gonzalez, Department of Psychiatry, University of California San Diego, La Jolla, United States
Lauren Edwards, SDSU/UCSD Joint Doctoral Program in Clinical Psychology, San Diego, United States
Kelsey Thomas, Research Service, VA San Diego Healthcare System, San Diego, United States
Maria Bordyug, Department of Psychiatry, University of California San Diego, La Jolla, United States
Einat Brenner, Department of Psychiatry, University of California San Diego, La Jolla, United States
Uriel Urias, Department of Psychology, San Diego State University, San Diego, United States
Katherine Bangen, Department of Psychiatry, University of California San Diego, La Jolla, United States

Category: Dementia (Alzheimer's Disease)

Keyword 1: activities of daily living
Keyword 2: cognitive course
Keyword 3: aging disorders

Objective:

Objectively-defined subtle cognitive decline (Obj-SCD) is an emerging classification that may identify individuals at risk for future decline and progression to Alzheimer’s disease (AD) prior to a diagnosis of mild cognitive impairment (MCI). Synaptic loss and neurodegeneration are part of the AD pathophysiologic process and may relate to cognition more closely than amyloid-β (Aβ) plaques and neurofibrillary tangles (NFT). Growth-associated protein 43 (GAP-43), a CSF marker of synaptic dysfunction, has been shown to relate to increased risk of converting to dementia although it is unclear whether GAP-43 alterations may be detected in pre-MCI stages. Therefore, in the present study we examined CSF GAP-43 levels among individuals with Obj-SCD cross-sectionally and also examined whether baseline GAP-43 predicts future functional decline.

Participants and Methods:

Participants included older adults from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) with CSF GAP-43 data available. Participants were divided into 6 groups based on cognitive status (cognitively unimpaired (CU), Obj-SCD, or MCI) and whether they are Aβ negative or positive (+ or -) based on positron emission tomography (PET). Baseline measurements included a total of 653 participants: CU- (n = 171), SCD- (n = 74), MCI- (n = 98), CU+ (n = 95), SCD+ (n = 56), and MCI+ (n = 159). Analysis of variance (ANOVA) compared groups on baseline CSF GAP-43 levels adjusting for age and sex. Linear mixed effects models, adjusting for age, sex, and education, examined the 4-year rate of change in functional abilities (measured with the Functional Activities Questionnaire) by group as well as the extent to which baseline GAP-43 moderated this relationship.

Results:

ANOVA models showed that the CU- group had lower baseline GAP-43 than all biomarker positive groups. Baseline GAP-43 values did not differ between the CU- group and the other Aβ- groups. Mixed models showed a significant three-way interaction of GAP-43 x group x time such that higher GAP-43 at baseline predicted a steeper rate of decline for the MCI+ and Obj-SCD+ groups, compared to the CU- group.

Conclusions:

Results extend prior work investigating biomarker associations in Obj-SCD to GAP-43, and show that high baseline CSF GAP-43 is associated with a faster rate of functional decline in Aβ+ individuals who are classified as Obj-SCD or MCI. Importantly, our findings further demonstrate that CSF GAP-43 is associated with early and subtle cognitive changes detectable before onset of MCI.