Associations of Salivary Total Antioxidant Capacity With Cortical Amyloid-Beta Burden, Cortical Glucose Uptake, and Cognitive Function in Normal Aging.

BACKGROUND: Determining susceptibility to Alzheimer's disease (AD) in asymptomatic individuals requires from noninvasive, simple, and inexpensive markers that can be easily obtained in primary care settings. While saliva meets all these requirements, there is a lack of evidence linking salivary constituents to in vivo AD pathology in aging. METHODS: We examined the potential of salivary total antioxidant capacity (TAC) for identifying global cortical amyloid-beta (Aß) burden, deficits in regional glucose uptake, and poorer cognition in 71 cognitively normal older adults. We further assessed whether salivary TAC-related cognitive performance was associated with higher Aß load and lower cortical glucose consumption. RESULTS: Linear regression analyses adjusted by age, sex, years of education, and ApoE4 status showed that salivary TAC was associated with slower processing speed and poorer sustained attention, as well as with higher Aß load and lower glucose metabolism in cortical regions vulnerable to cognitive aging and AD. Results also revealed that lower scores in processing speed and sustained attention were associated with greater Aß burden and lower regional glucose consumption, respectively. CONCLUSIONS: Together, these findings support the use of salivary TAC for preventive screening and detection of cerebral vulnerability to AD. Further research is needed to evaluate the utility of salivary TAC as a clinical marker.

Blood total antioxidant status is associated with cortical glucose uptake and factors related to accelerated aging.

Identifying cerebral vulnerability in late life is of paramount importance to prevent pathological trajectories of aging before the onset of symptoms. Considerable evidence suggests that impaired antioxidant mechanisms are a fingerprint of aging-related conditions, but there is a lack of human research linking total antioxidant capacity (TAC) measured in peripheral blood to in vivo brain changes and other factors featuring accelerated aging. To address this issue, we have assessed in cognitively normal elderly subjects (N = 100) correlations between serum TAC, using the oxygen radical absorbance capacity assay, surface-based cortical thickness, surface-based 18F-fluorodeoxyglucose positron emission tomography cortical uptake, and different factors associated with accelerated aging [i.e., serum homocysteine (HCY), self-reported memory problems, and self-reported patterns of physical activity]. While no relationship was observed between serum TAC and variations in cortical thickness, decreased TAC level was significantly associated with lower FDG uptake in temporal lobes bilaterally. Remarkably, decreased TAC level was linked to increased HCY concentrations, more subjective memory complaints, and lower frequency of physical activity. Overall, our results suggest that decreased serum TAC level may be helpful to detect vulnerable trajectories of aging.

Decreased salivary lactoferrin levels are specific to Alzheimer's disease.

BACKGROUND: Evidences of infectious pathogens in Alzheimer's disease (AD) brains may suggest a deteriorated innate immune system in AD pathophysiology. We previously demonstrated reduced salivary lactoferrin (Lf) levels, one of the major antimicrobial proteins, in AD patients. METHODS: To assess the clinical utility of salivary Lf for AD diagnosis, we examine the relationship between salivary Lf and cerebral amyloid-ß (Aß) load using amyloid-Positron-Emission Tomography (PET) neuroimaging, in two different cross-sectional cohorts including patients with different neurodegenerative disorders. FINDINGS: The diagnostic performance of salivary Lf in the cohort 1 had an area under the curve [AUC] of 0•95 (0•911-0•992) for the differentiation of the prodromal AD/AD group positive for amyloid-PET (PET+) versus healthy group, and 0•97 (0•924-1) versus the frontotemporal dementia (FTD) group. In the cohort 2, salivary Lf had also an excellent diagnostic performance in the health control group versus prodromal AD comparison: AUC 0•93 (0•876-0•989). Salivary Lf detected prodromal AD and AD dementia distinguishing them from FTD with over 87% sensitivity and 91% specificity. INTERPRETATION: Salivary Lf seems to have a very good diagnostic performance to detect AD. Our findings support the possible utility of salivary Lf as a new non-invasive and cost-effective AD biomarker. FUNDING: Instituto de Salud Carlos III (FIS15/00780, FIS18/00118), FEDER, Comunidad de Madrid (S2017/BMD-3700; NEUROMETAB-CM), and CIBERNED (PI2016/01) to E.C.; Spanish Ministry of Economy and Competitiveness (SAF2017-85310-R) to J.L.C., and (PSI2017-85311-P) to M.A.; International Centre on ageing CENIE-POCTEP (0348_CIE_6_E) to M.A.; Instituto de Salud Carlos III (PIE16/00021, PI17/01799), to H.B.