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Background: Normal brain aging is associated with dopamine decline, which has been linked to age-related cognitive decline. Factors underlying individual differences in dopamine integrity at older ages remain, however, unclear. Here we aimed at investigating: (i) whether inflammation is associated with levels and 5-year changes of in vivo dopamine D2-receptor (DRD2) availability, (ii) if DRD2-inflammation associations differ between men and women, and (iii) whether inflammation and cerebral small-vessel disease (white-matter lesions) serve as two independent predictors of DRD2 availability.

Methods: Analyses were performed in a sample of healthy adults > 60 years assessed at two measurement occasions separated by 5 years. At both occasions, DRD2 availability was estimated by ¹¹C-raclopride PET, and white-matter lesions by MRI. Inflammation was assessed by two C-reactive protein-associated DNA methylation scores at study baseline.

Results: Individuals with higher DNA methylation scores at baseline showed reduced striatal DRD2 availability. An interaction was found between DNA methylation scores and sex in relation to striatal DRD2 availability, such that associations were found in men but not in women. DNA methylation scores at study entrance were not significantly associated with 5-year striatal DRD2 decline rates. No significant association was found between DNA methylation scores and white-matter lesions, but higher scores as well as higher lesion burden were independently associated with reduced striatal DRD2 availability in men.

Conclusions: These findings suggest negative associations between one proxy of inflammation and DRD2 availability in older adults, selectively for men who had higher DNA methylation scores. Future studies should investigate other inflammatory markers in relation to dopamine integrity.

OBJECTIVES: To provide an overview of patient and public involvement (PPI) in the mesolevel and macrolevel of healthcare (different from PPI in research) and identify directions for future research by mapping contexts, terminology, conceptual frameworks, measured outcomes and research gaps.

DESIGN: Mapping review of systematic reviews. A patient coresearcher (JB) was involved in all stages. A broad search strategy was applied to capture the variation in terminology.

DATA SOURCES: MEDLINE, CINAHL and PsycINFO were searched from 1 January 2001 to 5 December 2022.

ELIGIBILITY CRITERIA: We included systematic reviews of empirical studies focusing on PPI in the mesolevel and macrolevel of healthcare.

DATA EXTRACTION AND SYNTHESIS: Three independent reviewers used standardised methods to screen studies and extract data. Thematic categories were created inductively through iteration. The results were organised in narrative, visual or tabular formats.

RESULTS: 4419 identified records were screened. 37 systematic reviews were eligible for inclusion. Most studies were narrative syntheses (N=26). Identified context categories were PPI for healthcare quality improvement (22%), patient safety (8%), community-based initiatives (27%), peer support (16 %) and education of healthcare professionals (27%). A wide range of terms was used to discuss PPI, with community participation being the most common. 28 reviews reported on frameworks, conceptual guidance and/or policy documents. Nine different types of outcomes were identified. The research gap pointed out most frequently is the lack of studies of robust designs that allow for replication and long-term follow-up, followed by studies on cost-effectiveness and resources needed. There is a need for consensus on the use of terminology.

CONCLUSIONS: This mapping review sheds light on the evolving landscape of PPI in healthcare. To advance the field, future research should prioritise rigorous study designs, cost-effectiveness assessments and consensus-building efforts to create a more unified and impactful approach for PPI in healthcare.