Cholesterol and Dementia: A Long and Complicated Relationship

Abstract

Background: There is a huge demand for efficient strategies for maintaining cognitive wellbeing with age, especially in the context of population aging. Dementia constitutes the main reason for disability and dependency in the elderly. Identification of potential risk and protective factors, as well as determinants of conversion from MCI to dementia, is therefore crucial. In case of Alzheimer’s disease, the most prevalent dementia syndrome amongst the members of modern societies, neurodegenerative processes in the brain can begin many years before first clinical symptoms appear. First functional changes typically mean advanced neuron loss, therefore, the earliest possible diagnosis is critical for implementation of promising early pharmaceutical interventions. Objective: The study aimed to discuss the relationships between both circulating and brain cholesterol with cognition, and explore its potential role in early diagnosis of cognitive disorders. Methods: Literature review. Results: The causal role of high cholesterol levels in AD or MCI has not been confirmed. It has been postulated that plasma levels of 24(S)-OHC can potentially be used as an early biochemical marker of altered cholesterol homeostasis in the CNS. Some studies brought conflicting results, finding normal or lowered levels of 24(S)-OHC in dementia patients compared to controls. In spite of decades of research on the relationship between cholesterol and dementia, so far, no single trusted indicator of an early cognitive deterioration has been identified. Conclusion: The current state of knowledge makes the use of cholesterol markers of cognitive decline in clinical practice impossible

Statins and Alzheimer — current stand and further development directions

“…However, due to their pleiotropic effect, we should not limit their use. Experimental studies have shown that statins reduce Ab production, inhibit inflammatory reactions, protect neurons from neurotoxicity induced by pathological protein, and oxidative stress [8,16]. We divide statins according to their properties.…”

“…In the autopsy of brains affected by dementia, 24-OH reduction and 27-OH increase can be seen. Zuliani et al suggest that 24 (S)-hydroxychowww.journals.viamedica.pl/medical_research_journal lesterol levels may be elevated in the early stages of AD due to systemic inflammation [8]. It is suggested that 24S-hydroxycholesterol (SHC) is a biochemical marker of neurodegenerative diseases, as it is responsible for the transport of cholesterol through its enzymatic oxidation [1,27].…”

“…The work is focused on Alzheimer's disease, which accounts for 60-80% of dementia [8]. It is irreversible disease [4], manifested by loss of memory, speech, and cognitive functions, progressing over the years [8]. Most patients have first symptoms before 65 years of age and fully manifest in 30-50% before 85 years of age.…”

“…However, only 2-10% of patients develop the disease earlier. The main pathological features of brain AD are intracellular neurofibrillary tangles of phosphorylated tau protein, which are believed to have a greater role in pathology [4,9,10] and supernormal extracellular accumulation of beta-amyloid protein in amyloid plaques [5] and loss of cholinergic neurons [8]. Changes are correlated with synapses loss and neuronal death [11].…”

“…APOE e4, PS1 and PS2 [13,14]. Tissue changes precede the appearance of clinical symptoms for many years and neuropathological changes can be found in people who currently have no symptoms [8]. Numerous works are trying to answer the question of whether statins are suitable for Alzheimer's therapy [15] -we want to answer why they can be suitable.…”