Year: 2019
Type: article
Study design: Observational Study
Abstract: Alzheimer's disease-like patterns of brain amyloid can be found in cognitively intact older adults. Initial amyloid deposits appear in perirhinal cortex and spread to the subiculum, CA1 of the hippocampus, and the fascia dentata before spreading throughout the cortex. We hypothesized that lower cerebrospinal fluid (CSF) levels of amyloid beta 1–42 (Aβ42) - indicating greater brain amyloid deposition - would be associated with smaller hippocampal subregional volumes on high-resolution MRI scans. We obtained hippocampal high-resolution (0.4×0.4×2.0 mm; Siemens Prisma 3T) scans for 56 non-demented older adults (67.9 ± 7.3 years old; Clinical Dementia Rating – CDR- global score 0 in 44; 0.5 in 7; pending in 5) from the USC ADRC. We used Automatic Segmentation of Hippocampal Subfields (ASHS) software with a study-specific atlas to segment the entorhinal cortex (ERC), subiculum, CA1 of the hippocampus, and a region that included CA2, CA3, and dentate gyrus (CA23DG). One reviewer edited subregions blinded to participant measures. We used multiple linear regressions to relate mean bilateral subregional volumes to CSF Aβ42 levels, controlling for age, sex, and intracranial volume. For significant correlations, we further evaluated this relationship in the 44 cognitively intact adults (CDR 0). Bilateral CA1volume (omnibus p = 0.0006; β = 0.14, Aβ42 partial p=0.011), subiculum volume (omnibus p = 0.0014; β = 0.10, Aβ42 partial p=0.012), and CA23DG volume (trend omnibus p = 0.0065; β = 0.13, Aβ42 partial p=0.07) but not bilateral ERC volume, were larger in those with higher CSF Aβ42 levels, indicating less brain amyloid deposition. Bilateral CA1 and subiculum volumes and CSF Aβ42 were not correlated with number of APOE4 alleles in the 46 people for whom genotypes were available. In 44 CDR 0 participants, CSF Aβ42 levels remained correlated with subiculum volume (omnibus p = 0.005; β = 0.11, Aβ42 partial p=0.012); CA1 volume had trend level significance (omnibus p = 0.017; β = 0.09, Aβ42 partial p=0.099). In additional tests, subregions were not significantly associated with CSF tau or ptau181. Subiculum and CA1 volumes are correlated with CSF Aβ42 in non-demented older adults, and may serve as a useful non-invasive biomarker in intervention studies.
Source: Alzheimer s & Dementia
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2980578657