Relationship between cognitive performance and cortical gray matter in patients with subjective cognitive decline and mild cognitive impairment according to the AT(N) classification

Author(s)

Brenda Costa Gonçalves

• Document type: Master's Dissertation
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas
• Defense date: 2024-02-06

Examining board members

Marcio Luiz Figueredo Balthazar; Ivani Brys; Raphael Fernandes Casseb

• Advisor: Marcio Luiz Figueredo Balthazar

Abstract

Introduction: The construct of Alzheimer's Disease (AD) is considered a continuum, with pre-dementia phases characterized by Mild Cognitive Impairment (MCI) and Subjective Cognitive Decline (DCS). In research, AD began to be seen as a biological construct, with the possibility of in vivo diagnosis through biomarkers. The AT(N) classification is a descriptive system created to categorize the presence of the three main AD biomarkers: A - ?A peptide, T - tau protein, and N - neurodegeneration. Therefore, knowing the anatomical and cognitive patterns within this systematization is important for better characterization of patients with DCS and MCI, since the AT(N) classification is still quite recent and can be better explored. Objective: to characterize cognitive performance and gray matter thickness in patients with DCS and MCI, classified according to the AT(N) system. Materials and Methods: n=72 (16 DCS and 56 CCL). All participants underwent medical screening, neuropsychological assessment (memory: RAVLT and CFT-REY; attention/executive functions: TMT A and B; verbal fluency: phonemic and semantic), magnetic resonance imaging (MRI) exams, blood collection and cerebrospinal fluid (CSF). They were then categorized into 3 subgroups: normal biomarkers for AD [A-T-(N)-] (n=27); AD continuum (any profile with the A+ combination) (n=37) and suspected pathological changes unrelated to AD (SNAP), with profiles A-T+(N)-, A-T-(N)+ and A-T+( N)+ (n=8). In the statistical analysis, a MANOVA was first performed to evaluate the difference in neuropsychological compounds (memory, attention, and executive functions) between AT(N) groups, and post-hoc ANCOVA tests were performed for each of the compounds. Next, a linear regression was performed to verify differences in gray matter between the AT(N) groups, with correction for multiple comparisons. Finally, the correlation between neuropsychological compounds and gray matter of the AT(N) subtypes was verified, also followed by correction for multiple comparisons. Results: In the attention/executive functions composite, there was a significant difference in the SNAP group (p < 0.05), which had lower performance compared to the others. In the memory and verbal fluency composites, there was no significant difference between the AT(N) groups, p = 0.91 and p = 0.07, respectively. In the analysis of the correlation between the neuropsychological compounds and the cortical gray matter, although there was no significance after adjusting for multiple comparisons when considering the uncorrected p-value < 0.001 for exploratory purposes, we found a correlation between the left fusiform gyrus and the left fusiform gyrus. memory composite in the DA continuum group. Conclusion: the SNAP group had a lower performance on the attention/executive functions composite, compared to the BN and DA continuum groups. There was more cortical gray matter atrophy in the AD continuum group compared to SNAP in the caudal anterior cingulate (CCA) and left cuneus. Furthermore, there was a positive correlation between memory performance and the left fusiform gyrus in the DA continuum group (AU)

• FAPESP's process: 20/02140-8 - Correlations between cognitive performance and cortical gray matter in patients with subjective cognitive decline and mild cognitive impairment according to AT(N) classification
• Grantee: Brenda Costa Gonçalves
• Support Opportunities: Scholarships in Brazil - Master