Dataset Information

Longitudinal hippocampal subfields, CSF biomarkers, and cognition in patients with Parkinson disease.

ABSTRACT:

Objective

Hippocampal atrophy is an indicator of emerging dementia in PD, though it is unclear whether cerebral spinal fluid (CSF) Abeta-42, t-tau, or alpha-syn predict hippocampal subfield atrophy in a de novo cohort of PD patients. To examine whether levels of CSF alpha-synuclein (alpha-syn), beta-amyloid 1-42 (Abeta-42)_, or total-tau (t-tau) are associated with hippocampal subfield volumes over time.

Methods

We identified a subset of Parkinson's Progression Markers Initiative (PPMI) de novo PD patients with longitudinal T1-weighted imaging (baseline plus at least two additional visits across 12, 24, and 48 months) and CSF biomarkers available at baseline. We performed cross-sectional, regression, and linear mixed model analyses to evaluate the baseline and longitudinal CSF biomarkers, hippocampal subfields, and cognition. A false discovery rate (FDR) was used to correct for multiple comparisons.

Results

88 PD-CN and 21 PD-MCI had high quality longitudinal data. PD-MCI patients exhibited reduced bilateral CA1 volumes relative to PD-CN, though there were no significant differences in CSF biomarkers between these groups. Relationships between CSF biomarkers and hippocampal subfields changed over time, with a general pattern that lower CSF Abeta-42, higher t-tau and higher alpha-syn were associated with smaller hippocampal subfields, primarily in the right hemisphere.

Conclusion

We replicated prior reports that demonstrated reduced CA1 volumes in PD-MCI in a de novo PD cohort. CSF biomarkers were associated with individual subfields, with evidence that the increased CSF t-tau was associated with smaller subiculum volumes at baseline and over time, though there was no clear indication that the subfields associated with cognition (CA1 and HATA) were associated with CSF biomarkers.

SUBMITTER: Erhardt E

PROVIDER: S-EPMC10724830 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Publications

Longitudinal hippocampal subfields, CSF biomarkers, and cognition in patients with Parkinson disease.

Erhardt Erik E Horner Anna A Shaff Nicholas N Wertz Chris C Nitschke Stephanie S Vakhtin Andrei A Mayer Andrew A Adair John J Knoefel Janice J Rosenberg Gary G Poston Kathleen K Suarez Cedeno Gerson G Deligtisch Amanda A Pirio Richardson Sarah S Ryman Sephira S

Clinical parkinsonism & related disorders 20230505

<h4>Objective</h4>Hippocampal atrophy is an indicator of emerging dementia in PD, though it is unclear whether cerebral spinal fluid (CSF) Abeta-42, t-tau, or alpha-syn predict hippocampal subfield atrophy in a <i>de novo</i> cohort of PD patients. To examine whether levels of CSF alpha-synuclein (alpha-syn), beta-amyloid 1-42 (Abeta-42)<sub>,</sub> or total-tau (t-tau) are associated with hippocampal subfield volumes over time.<h4>Methods</h4>We identified a subset of Parkinson's Progression Ma ...[more]

PMID: 38107672

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Project description:Altered hippocampal morphology and metabolic pathology, but also hippocampal circuit dysfunction, are established phenomena seen in psychotic disorders. Thus, we tested whether hippocampal subfield volume deficits link with deviations in glucose metabolism commonly seen in early psychosis, and whether the glucose parameters or subfield volumes change during follow-up period using one-year longitudinal study design of 78 first-episode psychosis patients (FEP), 48 clinical high-risk patients (CHR) and 83 controls (CTR). We also tested whether hippocampal morphology and glucose metabolism relate to clinical outcome. Hippocampus subfields were segmented with Freesurfer from 3T MRI images and parameters of glucose metabolism were determined in fasting plasma samples. Hippocampal subfield volumes were consistently lower in FEPs, and findings were more robust in non-affective psychoses, with strongest decreases in CA1, molecular layer and hippocampal tail, and in hippocampal tail of CHRs, compared to CTRs. These morphometric differences remained stable at one-year follow-up. Both non-diabetic CHRs and FEPs had worse glucose parameters compared to CTRs at baseline. We found that, insulin levels and insulin resistance increased during the follow-up period only in CHR, effect being largest in the CHRs converting to psychosis, independent of exposure to antipsychotics. The worsening of insulin resistance was associated with deterioration of function and symptoms in CHR. The smaller volume of hippocampal tail was associated with higher plasma insulin and insulin resistance in FEPs, at the one-year follow-up. Our longitudinal study supports the view that temporospatial hippocampal subfield volume deficits are stable near the onset of first psychosis, being more robust in non-affective psychoses, but less prominent in the CHR group. Specific subfield defects were related to worsening glucose metabolism during the progression of psychosis, suggesting that hippocampus is part of the circuits regulating aberrant glucose metabolism in early psychosis. Worsening of glucose metabolism in CHR group was associated with worse clinical outcome measures indicating a need for heightened clinical attention to metabolic problems already in CHR.

Dataset Information

Longitudinal hippocampal subfields, CSF biomarkers, and cognition in patients with Parkinson disease.

Objective

Methods

Results

Conclusion

Publications

Longitudinal hippocampal subfields, CSF biomarkers, and cognition in patients with Parkinson disease.

Similar Datasets

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