Interplay Between Age and Neuroinflammation in Multiple Sclerosis: Effects on Motor and Cognitive Functions

Abstract

Aging is one of the main risk factors for the development of many neurodegenerative diseases. Emerging evidence has acknowledged neuroinflammation as potential trigger of the functional changes occurring during normal and pathological aging. Two main determinants have been recognized to cogently contribute to neuroinflammation in the aging brain, i.e., the systemic chronic low-grade inflammation and the decline in the regulation of adaptive and innate immune systems (immunosenescence, ISC). The persistence of the inflammatory status in the brain in turn may cause synaptopathy and synaptic plasticity impairments that underlie both motor and cognitive dysfunctions. Interestingly, such inflammation-dependent synaptic dysfunctions have been recently involved in the pathophysiology of multiple sclerosis (MS). MS is an autoimmune neurodegenerative disease, typically affecting young adults that cause an early and progressive deterioration of both cognitive and motor functions. Of note, recent controlled studies have clearly shown that age at onset modifies prognosis and exerts a significant effect on presenting phenotype, suggesting that aging is a significant factor associated to the clinical course of MS. Moreover, some lines of evidence point to the different impact of age on motor disability and cognitive deficits, being the former most affected than the latter. The precise contribution of aging-related factors to MS neurological disability and the underlying molecular and cellular mechanisms are still unclear. In the present review article, we first emphasize the importance of the neuroinflammatory dependent mechanisms, such as synaptopathy and synaptic plasticity impairments, suggesting their potential exacerbation or acceleration with advancing age in the MS disease. Lastly, we provide an overview of clinical and experimental studies highlighting the different impact of age on motor disability and cognitive decline in MS, raising challenging questions on the putative age-related mechanisms involved.

Telomere Length Is Associated with Disability Progression in Multiple Sclerosis

“…41 This general marker of biological aging was associated with progression, although aging processes specific to the CNS may also be implicated. 42 The observation that telomere length, a somatic marker of biological aging, contributes to MS disability is consistent with our prior work on reproductive aging in women with MS. Levels of anti-Mullerian hormone, which correlate with ovarian aging and function, were associated with disability and brain volumes in cross section and over time. 43 Taken together, these studies suggest that targeting aging-related mechanisms may be a potential therapeutic strategy in MS to delay disability progression.…”

“…In this study, LTL was used as a general marker of biological aging as previously done in several conditions including cardiovascular disease and dementia, even though LTL can vary across cell types . This general marker of biological aging was associated with progression, although aging processes specific to the CNS may also be implicated …”

Theta burst stimulation influence the expression of BDNF in the spinal cord on the experimental autoimmune encephalomyelitis

“…Major pathological processes in the central nervous system (CNS) during multiple sclerosis (MS) are neuronal inflammation and neurodegeneration [31]. Developing techniques directed to protect neuron structure and function; decreasing perivascular inflammation and supporting blood/brain barrier (BBB) integrity are promising in MS analogous CNS disease, i.e.…”

Vanishing Pseudotumoral White Matter Lesions Presenting as Aphasia and Altered Mental Status in a 71-Year-Old Male

“…Even though these characteristics favored the diagnosis of late-onset monophasic ADEM at an early stage, this diagnosis was only possible after a period of observation after which the patient remained stable and with no further clinical or radiological activity. Late-onset MS seems to be related to a higher probability of primary progressive disease rather than a relapsing-remitting course as well as a rapid progression to secondary progressive phase from onset [13].…”