Abstract
Immunosenescence, vascular aging, and brain aging, all characterized by elevated levels of inflammatory markers, are thought to share a common pathogenetic pathway: inflamm-aging. Retrospective cross-sectional analysis was conducted using data from the Mugello study (Tuscany, Italy), a representative Italian cohort of free-living nonagenarians. to assess the association between specific peripheral inflammation markers derived from white blood cell counts, and the diagnosis of dementia. All the variables of interest were reported for 411 subjects (110 males and 301 females) out of 475 enrolled in the study. Anamnestic dementia diagnosis was obtained from clinical certificate and confirmed by a General Practitioner, whereas leukocyte ratios were directly calculated from white blood cell counts. Body mass index and comorbidities were considered potential confounders. Diagnosis of any type dementia was certified in 73 cases (17.8%). Subjects affected by dementia were older, more frequently reported a previous stroke, had lower body mass index, and lower Mini-Mental-State-Examination score. Moreover, they had a higher lymphocyte count and lymphocyte-to-monocyte ratio compared to the non-demented nonagenarians. We found that higher levels of lymphocyte counts are cross-sectionally associated with a clinical diagnosis of dementia. Furthermore, lymphocyte-to-monocyte ratio is directly associated with any type of dementia, independently of age, sex, lymphocyte count, and comorbidities. Lymphocyte-to-monocyte ratio may be considered a marker of immunological changes in the brain of dementia patients; moreover, it is low-cost, and easily available, thus enabling comparisons among different studies and populations, although the timeline and the extent of lymphocyte-to-monocyte ratio role in dementia development must be further investigated.
Highlights
Dementia is a chronic, progressive syndrome affecting both cognitive and functional abilities, representing one of the major causes of disability and dependency among older people
In a free living “young-old” population, the Rotterdam study reported an increase of Neutrophils and contextually a decrease of lymphocyte absolute numbers, with dementia patients showing a higher activation of the innate immune system, measured by different leukocytes ratios, compared to controls [14]
Lymphocyte count was higher in the dementia-group compared to the non-dementia-group (2.04 ± 1.24 vs 1.75 ± 0.72; p value = 0.006); no differences were found in all other markers (RBC, white blood cell (WBC), monocytes, platelets, hemoglobin, and hematocrit), adjusting analysis for age and sex between the two study groups (Table 1)
Summary
Progressive syndrome affecting both cognitive and functional abilities, representing one of the major causes of disability and dependency among older people. GeroScience due to multiple systemic inflammatory events [6], and in the earliest silent dementia phase, in response to intraneuronal accumulation of oligomeric peptides, neurotoxic cytokines are released [7]: in this inflammatory scenario, microglia are activated [8], driving further proinflammatory conditions which in turn induce an anti-inflammatory response [9] The progression of these processes culminates with the imbalance between adaptive/innate immune response, CNS invasion by peripheral monocytes [10], lymphocyte proliferation [7], and hyperactivation of microglial phagocytic cells [2]. In a free living “young-old” population (mean age 61 years), the Rotterdam study reported an increase of Neutrophils and contextually a decrease of lymphocyte absolute numbers, with dementia patients showing a higher activation of the innate immune system, measured by different leukocytes ratios, compared to controls [14] To date, these associations have not been explored within a representative oldestold population sample
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