Age and sex differences in frontal lobe cerebral oxygenation in older adults—Normative values using novel,scalable technology: Findings from the Irish Longitudinal Study on Ageing (TILDA)

AimsNear-infrared spectroscopy (NIRS) is a non-invasive, easy to apply, optical technology for measuring cerebral blood oxygenation, but there is lack of comprehensive population data to aid interpretation and clinical use. Given the importance of cerebral perfusion in the context of evolving guideline recommendations for more aggressive lowering of blood pressure (BP) in hypertension, even in the oldest old, understanding of normative NIRS values is timely. We estimated normative values of cerebral oxygenation measured by NIRS in a large community-dwelling population sample of adults aged > = 50 years (n = 3110). We hypothesized that measurements would be attenuated by cardiovascular risk factors.MethodsData from Wave 3 of The Irish Longitudinal Study on Ageing (TILDA) was utilized. Frontal lobe cerebral oxygenation was continuously measured via a Portalite, while participants rested in the supine position. Beat-to-beat BP was measured simultaneously. Normative data was modelled using generalized additive models for location, scale, and shape (GAMLSS). Multivariate linear regressions were used to examine associations with cardiovascular risk factors.ResultsAll three measures of NIRS (TSI, O2Hb and HHb) declined with increasing age. O2Hb and HHb were significantly lower in males than females. Increased smoking, excess alcohol intake, a higher waist-hip ratio, diabetes, angina, congestive heart failure, transient ischemic attack and total cardiovascular disease burden were all associated with decreased cerebral oxygenation.ConclusionWe present for the first time, normative resting-state NIRS reference data from a large population, which contributes to clinical interpretation of NIRS and advances the use of NIRS as a standard clinical tool.     

Differentiating early Parkinson's disease and multiple system atrophy with parkinsonism by saccade velocity profiles

ObjectivePatients with Parkinson's disease (PD) and multiple system atrophy both present predominantly with parkinsonism at early stages, whereas cerebellar symptoms are largely masked in multiple system atrophy with parkinsonism (MSAP). We sought to determine whether the velocity profiles of saccades could be used to differentiate between these two disorders, revealing the underlying basal ganglia and/or cerebellar dysfunction and brainstem pathology in these disorders.MethodsSixteen MSA-P patients, 63 PD patients, and 36 age-matched normal subjects performed the visually guided (VGS) and memory-guided saccade (MGS) tasks. Targets were presented at eccentricities of 5, 10, 20, and 30 degrees. The amplitude, peak velocity, and duration of saccades were compared among subject groups. Duration was further subdivided into acceleration and deceleration periods, corresponding to the times before and after peak velocity. These parameters correlated with the severity of Parkinsonism as assessed by the UPDRS motor score.ResultsHypometria predominated in both PD and MSAP patients, whereas hypermetria, frequently noted in cerebellar ataxia, was rarely observed. Saccades in MSAP were characterized both by prolonged acceleration and deceleration periods with reduced peak velocity. In contrast, the velocity profile of PD patients was characterized mainly by the prolonged deceleration period. The changes observed in velocity profiles of MGS deteriorated with advancing severity of parkinsonism in MSAP and PD patients.ConclusionSaccade profiles provide useful information for differentiating between PD and MSAP at early stages. While the changes in velocity profiles may be explained by the cerebellar and brainstem pathology in MSAP, the changes in velocity profile in both PD and MSAP correlated significantly with increasing severity of Parkinsonism in both disorders, suggesting a link with striatonigral pathology.SignificanceThe differential changes in saccade velocity profiles of MSAP and PD may be used as a measure indexing the progression of cerebellar and basal ganglia dysfunction as well as for assessing the functional improvement when clinical treatment becomes available.     

Corneal nerve microstructure in Parkinson’s disease

Ocular surface changes and blink abnormalities are well-established in Parkinson’s disease. Blink rate may be influenced by corneal sub-basal nerve density, however, this relationship has not yet been investigated in Parkinson’s disease. This case-control study examined the ocular surface in patients with moderately severe Parkinson’s disease, including confocal microscopy of the cornea. Fifteen patients with moderately severe Parkinson’s disease (modified Hoehn and Yahr grade 3 or 4) and fifteen control participants were recruited. Ophthalmic assessment included slit-lamp examination, blink rate assessment, central corneal aesthesiometry and in vivo corneal confocal microscopy. The effect of disease laterality was also investigated. Of the 15 patients with Parkinson’s disease, ten were male and the mean age was 65.5 ± 8.6 years. The corneal sub-basal nerve plexus density was markedly reduced in patients with Parkinson’s disease (7.56 ± 2.4 mm/mm²) compared with controls (15.91 ± 2.6 mm/mm²) (p < 0.0001). Corneal sensitivity did not differ significantly between the patients with Parkinson’s disease (0.79 ± 1.2 mBAR) and the control group (0.26 ± 0.35 mBAR), p = 0.12. Sub-basal nerve density was not significantly different between the eye ipsilateral to the side of the body with most-severe motor symptoms, and the contralateral eye. There was a significant positive correlation between ACE-R scores and sub-basal corneal nerve density (R² = 0.66, p = 0.02). This is the first study to report a significant reduction in corneal sub-basal nerve density in Parkinson’s disease and demonstrate an association with cognitive dysfunction. These results provide further evidence to support the involvement of the peripheral nervous system in Parkinson’s disease, previously thought to be a central nervous system disorder.     

Wakayama Symposium: Peroxisome Proliferator-Activated Receptor-Gamma (PPARγ) and Meibomian Gland Dysfunction

Recently we have shown that mouse and human meibomian glands undergo specific age-related changes, including decreased acinar cell proliferation, acinar atrophy, and altered peroxisome proliferator-activated receptor gamma (PPARγ) localization from cytoplasmic-vesicular/nuclear in young mice and humans to nuclear in old mice and humans. Since PPARγ is a lipid-sensitive, nuclear receptor implicated in regulating adipocyte and sebocyte differentiation and lipogenesis, our findings suggest that PPARγ may be involved in modulating meibomian gland differentiation during aging. Based on these findings, we propose that aging of the meibomian gland results in downregulation of PPARγ, leading to decreased meibocyte differentiation and lipid synthesis, gland atrophy, and a hyposecretory meibomian gland dysfunction.