The Epidemiology of Alzheimer’s Disease Modifiable Risk Factors  and Prevention

Zhang, Xin‐Xing; Tian, Yuan; Wang, Z.-T.; Ma, Ya‐Hui; Tan, Lan; Yu, Jin‐Tai

doi:10.14283/jpad.2021.15

Cited by 257 publications

(240 citation statements)

References 119 publications

(124 reference statements)

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“…AD affects more than 50 million people, and medical management is still a challenge as its pathogenesis still needs to be explored (Zhang et al, 2021). The pathogenesis in AD is related to the aggregation of Aß plaques and hyperphosphorylation of the microtubule-associated protein, tau resulting in neurofibrillary FIGURE 2 | The regulatory mechanism of Nrf2 in AD.…”

Section: Role Of Nrf2 In Alzheimer's Diseasementioning

confidence: 99%

A Perspective on Nrf2 Signaling Pathway for Neuroinflammation: A Potential Therapeutic Target in Alzheimer's and Parkinson's Diseases

Saha¹,

Buttari²,

Profumo³

et al. 2022

Front. Cell. Neurosci.

101

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Neuroinflammation plays a pivotal role in Alzheimer's disease (AD) and Parkinson's disease (PD), the leading causes of dementia. These neurological disorders are characterized by the accumulation of misfolded proteins such as amyloid-ß (Aß), tau protein and α-synuclein, contributing to mitochondrial fragmentation, oxidative stress, and neuroinflammation. Misfolded proteins activate microglia, which induces neuroinflammation, expression of pro-inflammatory cytokines and subsequently facilitates synaptic damage and neuronal loss. So far, all the proposed drugs were based on the inhibition of protein aggregation and were failed in clinical trials. Therefore, the treatment options of dementia are still a challenging issue. Thus, it is worthwhile to study alternative therapeutic strategies. In this context, there is increasing data on the pivotal role of transcription factor NF- E2 p45-related factor 2 (Nrf2) on the redox homeostasis and anti-inflammatory functions in neurodegenerative disorders. Interestingly, Nrf2 signaling pathway has shown upregulation of antioxidant genes, inhibition of microglia-mediated inflammation, and improved mitochondrial function in neurodegenerative diseases, suggesting Nrf2 activation could be a novel therapeutic approach to target pathogenesis. The present review will examine the correlation between Nrf2 signaling with neuroinflammation in AD and PD.

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Section: Role Of Nrf2 In Alzheimer's Diseasementioning

confidence: 99%

A Perspective on Nrf2 Signaling Pathway for Neuroinflammation: A Potential Therapeutic Target in Alzheimer's and Parkinson's Diseases

Saha¹,

Buttari²,

Profumo³

et al. 2022

Front. Cell. Neurosci.

101

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“…9,10 Nevertheless, the association between bilateral oophorectomy and cognitive decline or dementia is not considered established and is not included in mainstream reviews or summaries of the literature on risk factors associated with dementia. [11][12][13] The major reasons for this lack of recognition are the association of age at which the bilateral oophorectomy is performed with cognitive decline or dementia and controversial data about the association of ET after oophorectomy with cognitive decline or dementia. 2,14 In this study, we addressed some limitations of previous studies by focusing on premature or early bilateral oophorectomy, focusing on mild cognitive impairment (MCI), and using a comprehensive cognitive battery (9 cognitive tests covering 4 domains).…”

Section: Introductionmentioning

confidence: 99%

Association of Premenopausal Bilateral Oophorectomy With Cognitive Performance and Risk of Mild Cognitive Impairment

et al. 2021

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IMPORTANCEThe associations of bilateral oophorectomy among premenopausal women, age at oophorectomy, and use of estrogen therapy after oophorectomy with cognitive performance later in life remain controversial. OBJECTIVE To investigate whether women who underwent premenopausal bilateral oophorectomy were at increased risk of mild cognitive impairment (MCI) and experienced decreased global or domain-specific cognitive performance. DESIGN, SETTING, AND PARTICIPANTSThis case-control study and cross-sectional study were made possible by combining data from the Mayo Clinic Study of Aging (MCSA) and the Rochester Epidemiology Project (REP) medical record-linkage system. The studies were conducted among a population-based sample in Olmsted County, Minnesota, consisting of 2732 women aged 50 to 89 years who participated in the MCSA study from 2004 to 2019 and underwent a clinical evaluation and comprehensive cognitive testing. Data were analyzed from January to May 2021. EXPOSURES Medical record documentation of bilateral oophorectomy abstracted from a medical record-linkage system (ie, REP). MAIN OUTCOMES AND MEASURES Odds of MCI and global or domain-specific z scores on cognitive tests were measured at the first MCSA visit. The median (IQR) lag time between bilateral oophorectomy performed before menopause and before age 50 years and cognitive evaluation was 30 (22-38) years. RESULTS Among 2732 women aged 50 to 89 years (median [IQR] age at evaluation, 74 [66-81] years) who participated in the MCSA, the case-control study included 283 women with MCI (10.4%) and 2449 women without cognitive impairment (89.6%). Bilateral oophorectomy before menopause and before age 46 years was associated with clinically diagnosed MCI (adjusted odds ratio [aOR], 2.21; 95% CI, 1.41-3.45; P < .001) compared with no bilateral oophorectomy. The presence of an association with MCI varied by surgical indication, with an association among 259women with bilateral oophorectomy before menopause and before age 50 years for the indication of benign ovarian condition (aOR, 2.43; 95% CI, 1.36-4.33; P = .003) but not for cancer or no ovarian condition. The presence of an association did not vary by estrogen therapy after bilateral oophorectomy, with associations among women aged less than 46 years with estrogen therapy (aOR, 2.56; 95% CI, 1.24-5.31; P = .01) and without estrogen therapy (aOR, 2.05; 95% CI, 1.18-3.52; P = .01). The cross-sectional study included 625 women with a history of bilateral oophorectomy (median [IQR] age, 75 [70-82] years) and 2107 women without a history of bilateral oophorectomy (median [IQR] age, 73 [65-80] years). Premenopausal bilateral oophorectomy was performed before age 46 years among 161 women and was associated with decreased global cognition z score (β, −0.17; 95% CI, −0.32 to −0.03; P = .02), attention and executive domain z score (β, −0.21; 95% CI, −0.36 (continued) Key Points Question Is bilateral oophorectomy performed before spontaneous menopause associated with later-life cognition? Findings In a case-control ...

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“…Alzheimer’s disease (AD) is the primary cause of dementia among the elderly, characterized by the gradual loss of memory and cognitive skills needed for day-to-day activities, and it is ranked as the fifth leading cause of death globally [ 1 ].…”

Section: Introductionmentioning

confidence: 99%

Cholesterol Dysmetabolism in Alzheimer’s Disease: A Starring Role for Astrocytes?

Staurenghi¹,

Giannelli²,

Testa³

et al. 2021

Antioxidants

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In recent decades, the impairment of cholesterol metabolism in the pathogenesis of Alzheimer’s disease (AD) has been intensively investigated, and it has been recognized to affect amyloid β (Aβ) production and clearance, tau phosphorylation, neuroinflammation and degeneration. In particular, the key role of cholesterol oxidation products, named oxysterols, has emerged. Brain cholesterol metabolism is independent from that of peripheral tissues and it must be preserved in order to guarantee cerebral functions. Among the cells that help maintain brain cholesterol homeostasis, astrocytes play a starring role since they deliver de novo synthesized cholesterol to neurons. In addition, other physiological roles of astrocytes are to modulate synaptic transmission and plasticity and support neurons providing energy. In the AD brain, astrocytes undergo significant morphological and functional changes that contribute to AD onset and development. However, the extent of this contribution and the role played by oxysterols are still unclear. Here we review the current understanding of the physiological role exerted by astrocytes in the brain and their contribution to AD pathogenesis. In particular, we focus on the impact of cholesterol dysmetabolism on astrocyte functions suggesting new potential approaches to develop therapeutic strategies aimed at counteracting AD development.

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The Epidemiology of Alzheimer’s Disease Modifiable Risk Factors and Prevention

Cited by 257 publications

References 119 publications

A Perspective on Nrf2 Signaling Pathway for Neuroinflammation: A Potential Therapeutic Target in Alzheimer's and Parkinson's Diseases

A Perspective on Nrf2 Signaling Pathway for Neuroinflammation: A Potential Therapeutic Target in Alzheimer's and Parkinson's Diseases

Association of Premenopausal Bilateral Oophorectomy With Cognitive Performance and Risk of Mild Cognitive Impairment

Cholesterol Dysmetabolism in Alzheimer’s Disease: A Starring Role for Astrocytes?

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