Low-grade systemic inflammation is associated with functional disability in elderly people affected by dementia

Abstract

The decline in basic and instrumental activities of daily living (BADLs and IADLs, respectively) is a well-established clinical hallmark of dementia. Growing evidence has shown that systemic subclinical inflammation may be related to functional impairment. We evaluated the possible association between low-grade systemic inflammation and functional disability in older individuals affected by dementia. We explored the association between high-sensitivity C-reactive protein (hs-CRP) levels and BADLs/IADLs in older individuals affected by late onset Alzheimer's disease (LOAD; n 110), "mixed" dementia (n 135), or mild cognitive impairment (MCI; n 258), and compared them with 75 normal Controls. Independent of age, gender, comorbidity, and other potential confounders, higher hs-CRP was significantly associated with poorer BADLs (loss ≥ 1 function) in people with LOAD (odds ratio [OR] 3.14, 95% confidence interval [CI], 1.33-7.33) and mixed dementia (OR 2.48, 95%CI 1.12-5.55), but not in those with MCI (OR 1.38, 95%CI 0.83-2.45) or Controls (OR 2.98, 95%CI 0.54-10.10). No association emerged between hs-CRP and IADLs in any of the sub-group. Our data suggest that systemic low-grade inflammation may contribute to functional disability in older patients with dementia.

Molecular and Clinical Issues about the Risk of Venous Thromboembolism in Older Patients: A Focus on Parkinson’s Disease and Parkinsonism

“…Beyond the calf muscle pump dysregulation that acts as a trigger for thrombotic events, chronic inflammation could itself mediate the risk of VTE in older patients through the functional limitation. Several studies have found that elderly patients, particularly women, with high levels of cytokines and inflammation markers such as IL-6 and CRP, had lower muscle strength and higher walking impairment than those with reduced serum levels [ 43 , 44 , 45 , 46 , 47 ].…”

“…Finally, subtle neurological signs are particularly prevalent [ 63 ] in older persons and their presence could be interpreted as the presence of multiple neurological disease related to aging, such as PD plus chronic vascular lesions related to hypertension [ 64 ], or normal pressure hydrocephalus associated with vascular lesions. Therefore, these chronic neurological diseases in older persons could change the trajectory of an isolated neurodegenerative disease if they are present simultaneously in older subjects [ 45 ]. Interestingly, postural abnormalities are associated with an increased DVT risk in PD patients.…”

Lipopolysaccharide exposure in a rat sepsis model results in hippocampal amyloid-β plaque and phosphorylated tau deposition and corresponding behavioral deficits

“…Whether lower levels of chronic or acute systemic inflammation may also have similar hippocampal effects is not known. There is supportive evidence that low-grade systemic inflammation does result in worsened functional disability in elderly patients with dementia (Cervellati et al 2018). In addition, neurocognitive impairment associated with the aging process in primates has been associated with neuroinflammatory features seen in the current rat sepsis model, such as microglial activation (Shobin et al 2017).…”

TDP-43 mediated blood-brain barrier permeability and leukocyte infiltration promote neurodegeneration in a low-grade systemic inflammation mouse model

“…After all, a vast array of toxic or allergenic substances, in addition to microbes, can threaten body homeostasis and launch the immune response as a protective mechanism, which can inadvertently harm the brain. In fact, given that a number of patients with neurodegenerative diseases present with low-grade systemic inflammation [12][13][14][15][16][17][18], it is not surprising that the altered immune response may affect brains with BBB abnormalities and/or impair neurovascular unit function leading to increased BBB permeability and peripheral cell infiltration.…”

“…Notably, many patients suffering from neurological disorders present a persistently heightened systemic inflammatory state referred to as low-grade systemic inflammation which is a risk factor for morbidity and mortality in the elderly [ 12 ]. Older patients with dementia, and even old individuals without dementia, experience low-grade systemic inflammation characterized by increased high-sensitivity C-reactive protein (hs-CRP) levels associated with increased cognitive decline [ 13 ]. A study by Miller et al showed an increased prevalence of the non-thyroid autoimmune disease in patients diagnosed as frontotemporal dementia with motor neuron disease and symptomatic C9ORF72 mutation carriers [ 14 ].…”