Background: In the last decade, several observational studies have suggested that there exists an association between periodontal disease (PD) and Alzheimer's disease (AD). The aim of this systematic review was to investigate whether or not this link exists. Summary: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis guideline for systematic review was used and registered at PROSPERO (CRD42016035377). The search strategy included using electronic databases and by hand searching articles published up to January 2016. MEDLINE via PubMed, EMBASE and Web of Science were searched by 2 independent reviewers. Observational studies including patients meeting criteria for both AD and PD were eligible to be included in the analysis. Quality assessment of selected studies was performed by the Newcastle-Ottawa Scale. From a total of 550 titles and abstracts, 5 studies were included (2 cross-sectional, 2 case-control and one cohort study) in the review. A fixed effects meta-analysis showed that the presence of PD is associated with the presence of AD (OR 1.69, 95% CI 1.21-2.35). When only severe forms of PD were evaluated, a significant association was also observed (OR 2.98, 95% CI 1.58-5.62). Key Messages: In the present review, a significant association was observed between PD and AD. Further studies should be carried out in order to investigate the direction of the association and factors that may confound it.

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Purpose Recent evidence suggests that PET imaging with amyloid-β (Aβ) tracers can be used to assess myelin integrity in cerebral white matter (WM). Alzheimer’s disease (AD) is characterized by myelin changes that are believed to occur early in the disease course. Nevertheless, the extent to which demyelination, as measured with Aβ PET, contributes to AD progression remains unexplored. Methods Participants with concurrent 18F-florbetapir (FBP) PET, MRI, and cerebrospinal fluid (CSF) examinations were included (241 cognitively normal, 347 Aβ-positive cognitively impaired, and 207 Aβ-negative cognitively impaired subjects). A subset of these participants had also available diffusion tensor imaging (DTI) images (n = 195). We investigated cross-sectional associations of FBP retention in the white matter (WM) with MRI-based markers of WM degeneration, AD clinical progression, and fluid biomarkers. In longitudinal analyses, we used linear mixed models to assess whether FBP retention in normal-appearing WM (NAWM) predicted progression of WM hyperintensity (WMH) burden and clinical decline. Results In AD-continuum individuals, FBP retention in NAWM was (1) higher compared with WMH regions, (2) associated with DTI-based measures of WM integrity, and (3) associated with longitudinal progression of WMH burden. FBP uptake in WM decreased across the AD continuum and with increasingly abnormal CSF biomarkers of AD. Furthermore, FBP retention in the WM was associated with large-calibre axon degeneration as reflected by abnormal plasma neurofilament light chain levels. Low FBP uptake in NAWM predicted clinical decline in preclinical and prodromal AD, independent of demographics, global cortical Aβ, and WMH burden. Most of these associations were also observed in Aβ-negative cognitively impaired individuals. Conclusion These results support the hypothesis that FBP retention in the WM is myelin-related. Demyelination levels progressed across the AD continuum and were associated with clinical progression at early stages, suggesting that this pathologic process might be a relevant degenerative feature in the disease course.

Circulating endothelial progenitor cells (EPCs) play a role in the regeneration of damaged brain tissue. However, the relationship between circulating EPC levels and functional recovery in intracerebral hemorrhage (ICH) has not yet been tested. Therefore, our aim was to study the influence of circulating EPCs on the outcome of ICH. Forty-six patients with primary ICH (males, 71.7%; age, 72.7 ± 10.8 years) were prospectively included in the study within 12 hours of symptom onset. The main outcome variable was good functional outcome at 12 months (modified Rankin scale ≤2), considering residual volume at 6 months as a secondary variable. Circulating EPC (CD34+/CD133+/KDR+) levels were measured by flow cytometry from blood samples obtained at admission, 72 hours and day 7. Our results indicate that patients with good outcome show higher EPC numbers at 72 hours and day 7 (all p < 0.001). However, only EPC levels at day 7 were independently associated with good functional outcome at 12 months (OR, 1.15; CI95%, 1.01–1.35) after adjustment by age, baseline stroke severity and ICH volume. Moreover, EPC levels at day 7 were negatively correlated to residual volume (r = −0.525; p = 0.005). In conclusion, these findings suggest that EPCs may play a role in the functional recovery of ICH patients.

Alzheimer’s disease (AD) is a neurodegenerative disease representing the most common type of dementia worldwide. The early diagnosis of AD is very difficult to achieve due to its complexity and the practically unknown etiology. Therefore, this is one of the greatest challenges in the field in order to develop an accurate therapy. Within the different etiological hypotheses proposed for AD, we will focus on the two-hit vascular hypothesis and vascular alterations occurring in the disease. According to this hypothesis, the accumulation of β-amyloid protein in the brain starts as a consequence of damage in the cerebral vasculature. Given that there are several vascular and angiogenic alterations in AD, and that endothelial progenitor cells (EPCs) play a key role in endothelial repair processes, the study of EPCs in AD may be relevant to the disease etiology and perhaps a biomarker and/or therapeutic target. This review focuses on the involvement of endothelial dysfunction in the onset and progression of AD with special emphasis on EPCs as a biomarker and potential therapeutic target.

Aim:To investigate whether periodontitis is associated with amyloid beta (Aβ) peptides and whether systemic inflammation could act as a potential mediator of this link. Materials and Methods:A case-control study was designed including 75 patients with periodontitis (cases) and 75 age-balanced and gender-matched participants without periodontitis (controls). Full-mouth periodontal evaluation was performed in all participants. Demographic, clinical and behaviour data were also recorded. Fasting blood samples were collected, and serum levels of interleukin 6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), Aβ 1-40 and Aβ 1-42 were determined.Results: Cases showed higher levels of IL-6 (8.7 ± 3.2 vs. 4.8 ± 0.5 pg/ml), hs-CRP (3.3 ± 1.2 vs. 0.9 ± 0.7 mg/L), Aβ 1-40 (37.3 ± 6.0 vs. 30.3 ± 1.8 pg/ml) and Aβ 1-42 (54.5 ± 10.6 vs. 36.5 ± 10.0 pg/ml) when compared to controls (all p < .001). Diagnosis of periodontitis was statistically significantly associated with cir-culating Aβ 1-40 ( coefficient adjusted = 6.9, 95% CI: 5.4-8.3; p < .001) and Aβ ( coefficient adjusted = 17.8, 95% CI: 14.4-21.3; p < .001). Mediation analysis confirmed hs-CRP and IL-6 as mediators of this association. Conclusions:Periodontitis is associated with increased peripheral levels of Aβ. This finding could be explained by enhanced systemic inflammation that can be seen in patients with periodontitis.

Patients suffering from periodontitis are at a higher risk of developing cognitive dysfunction. However, the mediation effect of an inflammatory diet and serum vitamin D levels in this link is unclear. In total, 2062 participants aged 60 years or older with complete periodontal diagnosis and cognitive tests from the National Health and Nutrition Examination Survey (NHANES) 2011–2012 and 2013–2014 were enrolled. The Consortium to Establish a Registry for Alzheimer’s disease (CERAD) word learning subtest (WLT) and CERAD delayed recall test (DRT), the animal fluency test (AFT) and the digit symbol substitution test (DSST) was used. Dietary inflammatory index (DII) was computed via nutrition datasets. Mediation analysis tested the effects of DII and vitamin D levels in the association of mean probing depth (PD) and attachment loss (AL) in all four cognitive tests. Periodontitis patients obtained worse cognitive test scores than periodontally healthy individuals. DII was negatively associated with CERAD-WLT, CERAD-DRT, AFT and DSST, and was estimated to mediate between 9.2% and 36.4% of the total association between periodontitis with cognitive dysfunction (p < 0.05). Vitamin D showed a weak association between CERAD-DRT, AFT and DSST and was estimated to between 8.1% and 73.2% of the association between periodontitis and cognitive dysfunction (p < 0.05). The association between periodontitis and impaired cognitive function seems to be mediated both by a proinflammatory dietary load and vitamin D deficiency. Future studies should further explore these mediators in the periodontitis-cognitive decline link.

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