gms | German Medical Science

Introduction: Sorting protein-related receptor with A-type repeats (SORLA; LR11) is a receptor involved in intracellular protein sorting that has recently gained attention as a protective factor against Alzheimer’s disease (AD) pathology, as it binds the amyloid precursor protein (APP) and prevents its breakdown into amyloidogenic peptides. Whether SORLA also plays a role in other neurodegenerative diseases, such as postoperative neurocognitive disorders (NCD), is presently unclear. Soluble shedded SORLA fragments in the circulation are believed to reflect levels of the intact receptor expressed in the brain. Here, we measured SORLA concentrations in preoperative plasma and determined associations with postoperative NCD in a sample of older adults who were free of clinical dementia.

Method: Data from 568 participants aged ≥65 years of the Biomarker Development for Postoperative Cognitive Impairment in the Elderly (BioCog) study were used. SORLA was measured in preoperative plasma using a in-house enzyme-linked immunosorbent assay (ELISA). Postoperative delirium (POD) was screened for twice daily between surgery and postoperative day 7/discharge. Postoperative cognitive dysfunction (POCD) was defined from repeat cognitive testing before surgery and at 3 months. Multiple logistic regression analyses associated SORLA concentrations with POD and POCD risk respectively, with adjustment for age, sex and surgery type. Sensitivity analyses stratified by obesity status (obese: body mass index, BMI≥30kg/m2; non-obese: BMI<30kg/m²).

Results: Of the 568 participants, 451 were non-obese (79.4%) and 117 (20.6%) were obese. Across the total analysis sample, 110 (19.4%) developed POD. Of 386 participants who returned for 3-month follow up, 47 (12.3%) had POCD. Across the total sample, SORLA was not associated with POD risk (OR per 100 ng/mL increase 1.03, 95% CI 0.96, 1.12, p=0.38) or with POCD risk (OR 1.03, 95% CI 0.92, 1.15, p=0.59). In the obese subgroup, a trend was observed for an association of higher SORLA and lower POD risk (OR 0.83, 95% CI 0.67, 1.03, p=0.09), whereas in the non-obese subgroup, a trend was observed for a higher SORLA and higher POCD risk (OR 1.09, 95% CI 1.00, 1.18, p=0.059). No other observations were made in the stratified analyses (all p>0.10). The analyses of the obese subgroup in particular were affected by reduced statistical power due to low analysis N.

Discussion: Circulating SORLA levels were not associated with POD or POCD, arguing against AD-type neuropathology involvement in these neuropsychiatric conditions. However, our sensitivity analyses suggests obesity-specific associations that warrant further investigation, including formal interaction analysis.

The authors declare that they have no competing interests.

The authors declare that a positive ethics committee vote has been obtained.