Statins Use in Alzheimer Disease: Bane or Boon from Frantic Search and Narrative Review

Abstract

Alzheimer's disease (AD) was used to describe pre-senile dementia to differentiate it from senile dementia, which develops in the adult age group of more than 65 years. AD is characterized by the deposition of amyloid beta (Aβ) plaque and tau-neurofibrillary tangles (TNTs) in the brain. The neuropathological changes in AD are related to the deposition of amyloid plaques, neurofibrillary tangles, and progression of neuroinflammation, neuronal mitochondrial dysfunction, autophagy dysfunction, and cholinergic synaptic dysfunction. Statins are one of the main cornerstone drugs for the management of cardiovascular disorders regardless of dyslipidemia status. Increasing the use of statins, mainly in the elderly groups for primary and secondary prevention of cardiovascular diseases, may affect their cognitive functions. Extensive and prolonged use of statins may affect cognitive functions in healthy subjects and dementia patients. Statins-induced cognitive impairments in both patients and health providers had been reported according to the post-marketing survey. This survey depends mainly on sporadic cases, and no cognitive measures were used. Evidence from prospective and observational studies gives no robust conclusion regarding the beneficial or detrimental effects of statins on cognitive functions in AD patients. Therefore, this study is a narrative review aimed with evidences to the beneficial, detrimental, and neutral effects of statins on AD.

Keywords: Alzheimer’s disease; cognitive functions; statins.

Figure 1

Pathophysiology of Alzheimer’s disease (AD): Amyloid plaques, mitochondrial dysfunction, formation of tau-neurofibrillary tangles, vascular amyloid, autophagy dysfunction, and cholinergic dysfunction are linked with AD neuropathology.

Figure 2

Neuropsychiatric disorders in Alzheimer’s disease (AD): Neuropsychiatric disorders in AD are interrelated disorders ranging from personality changes to severe cognitive dysfunction.

Figure 3

Drugs affecting the pathogenesis of Alzheimer’s disease (AD): Different modalities of drugs used in the management of AD. Anti-inflammatory, which reduces neuronal inflammation; γ secretase inhibitors, which attenuate neuronal degeneration; acetylcholine esterase (AChE) inhibitors, which prevent cholinergic synaptic dysfunction; and antioxidants, which prevent oxidative stress-induced neuronal degeneration in AD.

Figure 4

Chemical structure of statins (A): Rosuvastatin (B): Atorvastatin [26,27].

Figure 5

Detrimental effects of statins on Alzheimer’s disease (AD): Statins-induced AD are mediated through reduction of neuronal cholesterol with reduction of neuronal myelination. As well, statins lead to neuronal injury by inducing reduction of CoQ10 and worsening of preexisting cholesterol aberrations with induction of oxidative stress and mitochondrial dysfunction.

Figure 6

Beneficial effects of statins on Alzheimer’s disease (AD): Statins’ beneficial effects against development and progression of AD are mediated by different mechanisms including anti-inflammatory and antioxidant effects, modulation of Rho GPTase, inhibition synthesis and secretion of ApoE, and activation of α secretase pathway with reduced deposition of Aβ.