2Library and Information Access, San Diego State University, San Diego, CA, USA
Dementia is a term of medieval origin from the Latin demens meaning out of one’s mind . Contemporary usage of the term is a syndrome of progressive and persistent decline in multiple cognitive domains with associated changes in behavior, personality, and/or social functioning, produced by brain impairment. Senile dementia is the most common cause of dementia syndrome in a rapidly aging world. Memory impairment is the key cognitive domain, followed by frontal executive, language, and spatial dysfunctions. The most common dementia type associated with aging remains Alzheimer’s disease, followed by dementia with Lewy bodies and vascular dementia. Clinical features suggesting dementia with Lewy bodies include hallucinations, deficits in attention with fluctuations in cognition, mild Parkinsonism with progressive gait disorder and falls, and early visuospatial deficits; memory complaint or impairment is common, but less severe. Clinical features are mild memory impairment and mild behavioral changes. The diagnosis of vascular dementia is assisted by the presence of vascular risk factors and clinical and/or imaging evidence of strokes. Senile dementia is often a mix of these common dementia types. The dementia syndrome may also be caused by external insults (such as vasculitis, toxins, drugs, infectious agents, brain trauma, systemic organ failure) and caused by other systemic disorders, including disturbance in thyroid, vitamin, and calcium metabolism, although rarely.
Dementia fits into the unifying mechanism which has been widely applied, previously in an article involving electron transfer (ET), reactive oxygen species (ROS) and oxidative stress (OS) . This unifying mechanism argues that the preponderance of bioactive substances, usually as the metabolites, incorporate ET functionalities. We believe these ET-metabolites play an important role in physiological responses. The main group includes quinones (or phenolic precursors), metal complexes (or complexors), aromatic nitro compounds (or reduced hydroxylamine and nitroso derviatives), and conjugated imines (or iminimum species). Resultant redox cycling is illustrated in Scheme 1. In vivo redox cycling with oxygen can occur, giving rise to OS through generation of ROS, such as hydrogen peroxide, hydroperoxides, alkyl peroxides, and diverse radicals (hydroxyl, alkoxyl, hydroperoxyl, and superoxide) (Scheme 1). Cellular and mitochrondrial enzymes can also perform cataytically in the reduction of O2.
The major associate of dementia is AD, both of which are neurodegenerative disorders . AD is the common most reason for dementia in the elderly . There are various other reports that link the two illnesses [14-24]. In addition to these articles, there are assorted others that associate dementia with the unifying theme of ROS-OS-AO [25-30]. The literature deals with various drugs that are used for treatment of dementia. OS is believed to be the main risk for dementia and several of these studies deal with oxidative and AO markers in dementia patients [27-31]. Higher levels of AO power counter increased OS. Phenolics or their derivatives play important roles due to their AO and neuroprotective potential in the prevention of dementia, as in the case of PD and AD. Another important reference is a recent review concerning novel structure-activity relationship and quantitative data for phenolic drugs involving Alzheimer’s and Parkinson’s disease , which is applicable to dementia, as in importance of the substituent para to phenolic hydroxyl. Another factor is the presence of more than one phenolic group in the drugs discussed.
Caffeic acid phenethyl ester (CAPE) (Figure 1) is a natural polyphenolic substance attributed with AD immunomodulatory and neuroprotective properties . The drug arrested development of cognitive defecits in rats with dementia. Glutathione (GSH) content was enhanced, accompanied by decreased measure in rat
A 2014 study reported beneficial effects of α-lipoic acid (Figure 7) complex on rats with dementia . The supplementation of α-lipoic acid improved their AO status. Garlic, which contains sulfur AOs, such as allicin (Figure 8), has been studied extensively for health benefits . In a number of studies, garlic preparations protect neuronal cells against β -amylod toxicity and apoptosis . The broad range of AO and anti-apoptotic effects afforded by garlic also provides protection against dementia.
Simvastatin (Figure 9) exerts benefits in the progression of senile dementia . The drug regulates SOD, ROS, catalase and GSH in OS. Additionally, there is prevention of memory lapses. Hu-Yi-Neng, a diet supplement, including the AO ginko biloba, exerts a protective effect against OS . Non-drugs such as acupuncture [38,39] and certain vitamins  are also reported to exert a positive effect on dementia.
- Howell T. “Behavioral and psychological symptoms of dementia. In E. Capezuti. The Encyclopedia of Elder Care: The Comprehensive Resource on Geriatric Health and Social Care (3rd ed.). New York, NY”. Springer Publishing Company (2013).
- Dementia. “In Harvard Medical School (Ed.), Health Reference Series: Harvard Medical School Health Topics A-Z. Boston, MA”. Harvard Health Publications (2017).
- Kovacic P. “Unifying mechanism for nutrients as anticancer agents: Electron transfer, reactive oxygen species and oxidative stress”. Global Journal of Health Science 9.8(2017): 66-83.
- Kovacic P., et al. “Mechanisms of anticancer agents: Emphasis on oxidative stress and electron transfer”. Current Pharmaceutical Design: Ingenta Connect Publication 6 (2000): 277-309.
- Kovacic P., et al. “Reproductive toxins. Pervasive theme of oxidative stress and electron transfer”. Current Pharmaceutical Design: Ingenta Connect Publication 8 (2001): 863-892.
- Kovacic P., et al. “Cardiovascular toxicity from the perspective of oxidative stress, electron transfer, and prevention by antioxidants”. Current Pharmaceutical Design: Ingenta Connect Publication 3 (2005): 107-117.
- Kovacic P., et al. “Mechanism of mitochondrial uncouplers, inhibitors, and toxins: Focus on electron transfer, free radicals, and structure-activity relationships”. Current Pharmaceutical Design: Ingenta Connect Publication 12.22 (2005): 2601-2623.
- Kovacic P., et al. “Ototoxicity and noise trauma: Electron transfer, reactive oxygen species, cell signaling, electrical effects, and protection by antioxidants: Practical medical aspects”. Medical Hypotheses 70 (2008): 914-923.
- Halliwell B., et al. “Free Radicals in Biology and Medicine (3rd ed., Oxford science publications) Oxford: New York: Clarendon Press”. Oxford University Press (1999): 192-194.
- Kovacic P., et al. “Various factors involving aging: Electron transfer, reactive oxygen species and oxidative stress”. Current Pharmaceutical Design: Ingenta Connect Publication 9.7 (2017): 53518-53528.
- Howell T., et al. “Behavioral and psychological symptoms of dementia. In E. Capezuti. The Encyclopedia of Elder Care: The Comprehensive Resource on Geriatric Health and Social Care (3rd ed.). New York, NY: Springer Publishing Company (2013).
- Dementia. “In Harvard Medical School (Ed.), Health Reference Series: Harvard Medical School Health Topics A-Z”. Boston, MA: Harvard Health Publications (2017).
- Kovacic P., et al. “Cause and treatment of schizophrenia: Electron transfer, reactive oxygen species, oxidative stress, antioxidants, and unifying mechanism”. Chronicles of Pharmaceutical Science 1.6 (2017): 332-340.
- Gugliandolo A., et al. “Role of vitamin E in the treatment of Alzheimer's disease: Evidence from animal models”. International Journal of Molecular Sciences 18.12 (2017).
- Dey A., et al. “Natural products against Alzheimer's disease: Pharmaco-therapeutics and biotechnological interventions”. Biotechnology Advances 35.2 (2016): 178-216.
- Bhatti A.B., et al. “Vitamin supplementation as an adjuvant treatment for Alzheimer's disease”. Journal of Clinical and Diagnostic Research 10.8(2016).
- Sarkar S., et al. “Nanocapsulated ascorbic acid in combating cerebral ischemia reperfusion - induced oxidative injury in rat brain”. Current Alzheimer Research 13.12 (2016): 1363-1373.
- Zuo L., et al. “The role of oxidative stress-induced epigenetic alterations in amyloid-β production in Alzheimer's disease”. Oxidative Medicine and Cellular Longevity (2015).
- Suwanna N., et al. “Neuroprotective effects of diarylpropionitrile against β-amyloid peptide-induced neurotoxicity in rat cultured cortical neurons”. Neuroscience Letters 578 (2016): 44-49.
- Gubandru M., et al. “Alzheimer's disease treated patients showed different patterns for oxidative stress and inflammation markers”. Food and Chemical Toxicology 61 (2013): 209-214.
- Ferreiro E., et al. “Mitochondrial- and endoplasmic reticulum-associated oxidative stress in Alzheimer's disease: from pathogenesis to biomarkers”. International Journal of Cell Biology (2012): 735206.
- Choi DY., et al. “Antioxidant properties of natural polyphenols and their therapeutic potentials for Alzheimer's disease”. Brain Research Bulletin 87.2 (2012): 144-153.
- Bayati S., et al. “Protective effects of 1,3-diaryl-2-propen-1-one derivatives against H₂O₂ -induced damage in SK-N-MC cells”. Journal of Applied Toxicology 31.6 (2011): 545-553.
- Di Bona D., et al. “Immune-inflammatory responses and oxidative stress in Alzheimer's disease: therapeutic implications”. Current Pharmaceutical Design 16.6 (2010): 684-691.
- Taupin P. “A dual activity of ROS and oxidative stress on adult neurogenesis and Alzheimer's disease”. Central Nervous System Agents in Medicinal Chemistry 10 (2010): 16-21.
- Bennett S., et al. “Oxidative stress in vascular dementia and Alzheimer's disease: a common pathology”. Journal of Alzheimer's Disease 179.2 (2009): 245-257.
- Kumar M., et al. “Caffeic acid phenethyl ester (CAPE) prevents development of STZ-ICV induced dementia in rats”. Pharmacognosy Magazine 13.1 (2017).
- Ajith TA., et al. “Effect of palladium α-lipoic acid complex on energy in the brain mitochondria of aged rats”. Alternative Therapies In Health And Medicine 20.3 (2014): 27-35.
- Gironi M., et al. “Oxidative imbalance in different neurodegenerative diseases with memory impairment”. Neurodegenerative Diseases 8.3 (2011): 129-137.
- Shih YT., et al. “Arecoline, a major alkaloid of the areca nut, causes neurotoxicity through enhancement of oxidative stress and suppression of the antioxidant protective system”. Free Radical Biology & Medicine 49.10 (2010): 1471-1479.
- Wu SB., et al. “Mitochondrial DNA mutation-elicited oxidative stress, oxidative damage, and altered gene expression in cultured cells of patients with MERRF syndrome”. Molecular Neurobiology 41.2 (2-010): 256-266.
- Mathew B., et al. “Neuroprotective effects of garlic a review”. Libyan Journal of Medicine 3.1 (2008): 23-33.
- Yang YH., et al. “Neuroprotective effects of Hu-Yi-Neng, a diet supplement, on SH-SY5Y human neuroblastoma cells”. The Journal of Nutrition Health and Aging 18.2 (2014): 184-190.
- Kovacic P., et al. “Novel structure-activity relationship and quantitative data for phenolic drugs involving Alzheimer’s and Parkinson’s disease: Antioxidants, oxidative stress, and selectivity”. Chronicles of Pharmaceutical Science 1.5 (2017): 299-306.
- Zhang J., et al. “Puerarin attenuates cognitive dysfunction and oxidative stress in vascular dementia rats induced by chronic ischemia”. International Journal of Clinical and Experimental Pathology 8.5 (2015): 4695-4704.
- Li Y., et al. “Gastrodin improves cognitive dysfunction and decreases oxidative stress in vascular dementia rats induced by chronic ischemia”. International Journal of Clinical and Experimental Pathology 8.11(20145): 14099-14109.
- Yadav A., et al. “Resveratrol loaded solid lipid nanoparticles attenuate mitochondrial oxidative stress in vascular dementia by activating Nrf2/HO-1 pathway”. Neurochemistry International 112 (2018): 239-254.
- Clarke R., et al. “Effect of vitamins and aspirin on markers of platelet activation, oxidative stress and homocysteine in people at high risk of dementia”. Journal of Internal Medicine 254.1 (2013): 67-75.
- Liu W., et al. “Simvastatin ameliorates cognitive impairments via inhibition of oxidative stress‑induced apoptosis of hippocampal cells through the ERK/AKT signaling pathway in a rat model of senile dementia”. Molecular Medicine Reports 17.1 (2018): 1885-1892.
- Du SQ., et al. “Acupuncture inhibits TXNIP-associated oxidative stress and inflammation to attenuate cognitive impairment in vascular dementia rats”. CNS Neuroscience & Therapeutics | Neuroscience 24.1 (2018): 39-46.
- Li H., et al. “Acupuncture reversed hippocampal mitochondrial dysfunction in vascular dementia rats”. Neurochemistry International 92 (2016): 35-42.