Mild TBI in the elderly – risk factor for rapid cognitive impairment in Alzheimer’s disease

Abstract

In recent decades, traumatic brain injury (TBI) has become one of the most important health problems worldwide and is a major cause of morbidity, mortality and economic losses. Mild traumatic brain injury (mTBI) is less considered, with clinical underestimation leading to an epidemiological underevaluation of its incidence. Many of the signs and symptoms induced by mTBI are difficult to highlight clinically, especially those related to cognitive, behavioral, or emotional impairment. The complexity of the biological mechanisms induced by mTBI in the elderly determines synchronous pathogenic actions in which the vascular, inflammatory and neurodegenerative elements are intertwined. It is difficult to highlight a major pathogenic factor, since they act simultaneously, multimodally, in a real pathogenic cascade. The identification of mTBI and cerebral vascular changes by neuroimaging techniques, transcranial Doppler (TCD) or biological markers, suggests a potential prophylactic intervention by using neuroprotective factors as early as possible. Proper prophylaxis measures with neurotrophic treatment, rebalancing the gamma-aminobutyric acid (GABA)/glutamate balance and combating the chronic inflammatory process, can become important pharmacological therapeutic targets.

SARS-CoV-2 infection in patients with serious mental illness and possible benefits of prophylaxis with Memantine and Amantadine

“…The decrease in olfactory dysfunction may anticipate a rapid evolution from the mild cognitive impairment (MCI) stage to AD, but it can also be a marker for a negative evolution in schizophrenia, through the involvement of dopamine [ 93 ]. Decreased olfactory acuity on translational research is considered a valid pathogenic model for both AD and PD.…”

“…SARS-CoV-2 aggression on the central nervous system may be associated with increased cytokine storm intensity as the mechanism of activation of microglial structures occurs. The cytokine mechanisms are triggered by the activation of M1-type microglia, which trigger the production and high release of proinflammatory cytokines IL-1, IL-6, TNF- α , NO and ROS, to the detriment of neuroprotective M2 microglia, whose activity is related to anti-inflammatory cytokines IL-4, IL-10, IL-13 and transforming growth factor-beta (TGF- β ) [ 93 , 104 , 121 ]. The imbalance ratio M1/M2 microglia have an important role in pathogenesis of major psychiatric disorders, such as major depression, schizophrenia or bipolar disorder [ 122 ].…”

Neuroprotective effects of flavone luteolin in neuroinflammation and neurotrauma

“…48 Neurotrauma is a known risk factor for neurodegenerative diseases through TBIassociated secondary injury, and luteolin administration can protect from these neurodegenerative diseases. 49,50 Luteolin can inhibit neurotrauma/stroke-associated neuroinflammatory responses and protect neurons from secondary injury mechanisms in the brain. 42 Mast cells are abundantly present in the respiratory tract, gastrointestinal tract, skin, brain, meninges, and very close to blood vessels.…”

“…Additionally, luteolin can suppress the activation of NF‐kB, signal transducer and activator of transcription 3 (STAT3), c‐Jun N‐terminal kinases (JNK), p38, and extracellular signal‐regulated kinases 1/2 (ERK1/2) that are involved in the glial cell activation and inflammatory mediator release 48 . Neurotrauma is a known risk factor for neurodegenerative diseases through TBI‐associated secondary injury, and luteolin administration can protect from these neurodegenerative diseases 49,50 . Luteolin can inhibit neurotrauma/stroke‐associated neuroinflammatory responses and protect neurons from secondary injury mechanisms in the brain 42 …”

The Implications of Adverse Pharmacologic Reactions and Complex Pathogenic Mechanisms in Schizophrenia

“…This motor clinical presentation associates also non-motor symptomatology, represented especially by cognitive dysfunction, depression and dysautonomia, similar with the non-motor manifestation in Parkinson's disease (PD). Especially in cases of genetic vulnerability, dysautonomia may be exacerbated by mild TBI and cause disruption of dopaminergic transmission (Stovicek et al, 2020). The association of hyperhomocysteinemia, mild TBI and fetal alcoholism, determines a high risk for a neurodegenerative evolution as in Alzheimer's disease (AD) or PD (Campdelacreu, 2014).…”