Alzheimer’s disease (AD) has no known cause, cure, or universally accepted prevention strategy. Several studies have demonstrated that certain lifestyle choices are associated with a lower risk. It has also been reported that vascular risk factors and low neuroprotective factors are linked to cognitive decline and neurodegeneration. For instance, age, male gender, head injury, the presence of the epsilon 4 allele of apolipoprotein E (APOE e4), cognitive impairment, low levels of education, low neuroprotective factors, and vascular risk factors increase the risk of developing AD. The evidence of a gender difference in prevalence has been established: women live longer and are more likely to develop AD. The role of endogenous protective and risk factors is only partially known, especially in men.
Definition and Overview
The research in the available scientific literature revealed a great dispersion of results from different studies. Most authors found a relationship between periodontitis or oral health in general and AD. On the other hand, controversies existed about whether metals could or could not be considered risk factors. Concerning the presence or absence of an association with cholesterol and adiposity, in general, a positive correlation was found. However, authors only took into account the physical aspects of weight and not biochemical parameters. In any case, sports would be beneficial. Coffee and alcohol consumption can both be risk factors and protective factors. For other factors, it was not possible to establish any relationship from the data collected. We will continue our study along this line by introducing the necessary modifications.
Alzheimer’s disease (AD) is a neurodegenerative disease whose etiopathogenesis is still not clear. AD is the most common type of dementia in patients under 65-70 years old. There are some risk factors that may increase AD rates. These risk factors can be divided into genetic and environmental factors, among which are cardiovascular risk factors. Regarding this last point, results found in the literature are not always concordant. The aim of our study is to systematically review scientific articles studying environmental risk factors and/or protective factors of AD, specifically in males. The main method used for the study is the systematic review of articles obtained from a bibliographic search on the topic.
Epidemiology of Alzheimer’s Disease
Despite long-term recognition of the risk for Alzheimer’s disease (AD) and the substantial resources devoted to the study of its clinical expression and potential interventions market, the etiology of AD remains incompletely understood. Indeed, the causes of the disease have not been described at present. Presumably, the susceptibility to late-onset AD results from the complex interplay of multiple risk factors over a long lifespan. No seminal events have been identified that would precondition the brain for excessive deposition of amyloid-β (Aβ) late in life; however, it is suspected that genetic, behavioral, and environmental activities from the reproductive years to death are participating in decentralized effects upon AD risk. In an attempt to clarify unresolved questions regarding the epidemiology of AD, the International Working Group for Harmonization of Dementia Prevalence Surveys was convened to scrutinize available evidence and create summary consensus statements to guide future inquiries.
Prevalence in Men
Restricting a comparison of presumed AD – The most prevalent cause of dementia is AD, and it is reasonable to assume that many observational studies that do not identify the specific type actually refer to this disease. The higher case fatality of the disease among men reflects a longer time to diagnosis, greater difficulty in management, or a different relationship to the contributing factors to the disease. Men may be at a different evolutionary stage for AD development of AD-like changes in net arms in the presence of small amounts of Aβ, increasing the mortality rate somewhat.
Men with dementia are a vulnerable group and have care and support needs that are different from women. Although men are less likely to be affected by Alzheimer’s Disease (AD) than women, their condition is more severe at the time of diagnosis, with increased behavioral problems, suggesting a later stage of the disease when they are no longer able to manage themselves. Many diseases leading to deaths, although not associated causally with dementia, are possibly related factors that increase vulnerability to the disease, including behavioral problems, risk factors for poorer outcomes, and any underlying pathology. The different clinical pathway is supported by evidence from men without AD, showing a reduced ability to manage bathing compared with women. Men are also more likely to become socially isolated.
Risk Factors for Alzheimer’s Disease
The cause of AD is unknown and the only factor that has been consistently shown to increase the risk of late-onset AD is increasing age. Only about 1% of cases have a genetic basis, and it is thought that age-related metabolic variations underlie susceptibility to common late-onset AD, among many other diseases. Alternatively, genetic and environmental factors are thought to act in combination to increase the risk of developing the common form of AD. Other AD risk factors are described, however, risk factors for common AD cannot yet be predicted by the availability of laboratory tests. Age at onset is used for the categorization of the two primary forms of AD, early-onset AD (EOAD) and late-onset AD (LOAD), which have distinct risk factors and could also reflect underlying biological distinctions. EOAD is typically defined as onset before 65 years of age and clinically presents like the common LOAD in most cases. Characteristics of EOAD are an early age, genetic mutations, autosomal dominant inheritance, rapid disease progression, and biomarker presence. APOEε4 has been consistently shown to increase the risk of developing LOAD with a gene dose effect.
Genetic Factors
Due to ethical ramifications and/or the infeasibility of performing experimental studies in humans, there has been a shift in the emphasis for deciphering the pathophysiological mechanisms, from knowledge acquired through isolated genetic effects to the analysis of human neurobiological responses to the complex expression patterns associated with these genes, as a practical option by the use of large scale simultaneous assays.
Among four identified major genes associated with susceptibility to the aggressive variant, three of them code for proteins directly involved in the amyloid beta-peptide precursor amyloid A4 gene (APP) (amyloid beta-peptide, β-protein) processing (which is the major component of the senile plaque), probably altering the ratio between two alternative processing pathways that can lead to formation of a stable protein that participates in oxidative processes resulting in neuronal death. These genes are located on chromosomes 14 and 21. Although a cause-effect relationship could not be established, increased APP mRNA in AD brains and in neurons exposed to neurotoxins indicated that there is a connection between the levels of APP and the progression of AD. The fourth gene associated with susceptibility of AD contains the E4 allele of the apolipoprotein E (APOE) gene located on chromosome 19. It has been implicated in the development of both aggressive and late onset AD.
In recent years, molecular research performed on Alzheimer’s Disease (AD) cases and their relatives has provided much new information about this disease. Many genes are now known to be associated with susceptibility or with the aggressive variant of AD. However, the sporadic cases of AD are more common than the known hereditary forms. The apolipoprotein alpha 1 (APOA1) gene from the H2 haplotype has been suggested as a gene conferring risk in 40% to 50% of “sporadic” late onset AD cases.
Lifestyle Factors
Prospective studies in male populations show that physical activity and aerobic exercise reduce and may even prevent AD dementia. A second modifiable lifestyle factor is intellectual leisure activities positively impact the mechanisms that lead to cognitive decline and the Alzheimer pathology. This result suggests that leisure activities reduce or prevent cognitive symptoms. The most protective activities are those that demand that the individual may need to be engaged intellectually. Computer use in males might also prevent AD. Cognitive Reversal Activities perform cognitive activities early in old age. Older adults at high risk for AD may also retard the onset in those with an AD diagnosis. These activities are based on cognitive retraining and engagement in intellectual exercise. In a subsample of the inactive men with mild cognitive impairment, those who practice cognitive reversal activities for 12 weeks showed reduced brain hypoperfusion. The authors conclude that “cognitive artifacts” (that is, cognitive instrumental activities associated with intelligence, abstract reasoning, and long-term delayed recall) may constitute an important path that may affect cognitive performance and neuroanatomical activity and the conversion phase of SCD to mild cognitive impairment and/or AD. Humans require short-term memory affecting cognitive performance and opportunity for regional brain blood flow requirement. If patients with SCD are reporting a marked decline in cognitive backbone to areas affected by AD, suggesting cognitive impairments showed improvement during monitoring cognitive treatment. Also, Vander and Kessels conducted an investigation of a variety of individuals using a 40-hour intervention 21 30 minutes memory improvement both pre- and posttreatment. They found that automatically performed itemed the standard group-large list (SM) and test groups showed recognition of any non-distracted levels of recall ability, and postintervention scores, but significantly non-distracted Karnofsky performance status scores. The group gained from the cohort with SCD demonstrated significantly lower 3-week posttreatment scores have shown significant improvements in measured changes in the ray constant word recall scores first for SM, recognizing memory and brain hypoperfusion. These results indicated that using it is clear that cognition, effective early-stage treatment of patients affected by SCD can and the onset and/or termination of word recall activities-based stigmairno to 1. indicate onset and end signal SCD1)). cognitively converge development and even reverse mild cognitive impairment and/or sporadic AD early in their course. Cognitive prevention. These findings suggest that cognitive prevention of AD may be emerging as a unique cure that may ultimately benefit healthier aging across ages and genders at risk.
This section focuses on “modifiable” lifestyle behaviors that have been reliably linked to an increased risk for Alzheimer’s disease in men. Lower levels of educational attainment have been consistently linked to a higher risk for AD both in men and women. Early urbanization has a less clear association and has not been replicated in all studies. Occupational exposure to occupational hazards, such as highly demanding or monotonous work, have reliably linked to AD. Conditions of wealth in midlife may also constitute an AD risk factor.
Gender-Specific Risk Factors in Men
Alora et al. showed in their 2015 article that lower testosterone is associated with mild cognitive impairment (MCI). However, Tang et al. also cautioned against using supplemental testosterone to maintain bone and sexual function due to potential cognitive risks.
The mechanisms by which ADT induces cognitive changes are not fully understood, but a study by Tang et al. from 2017 emphasizes a role for androgens and estrogen doses. They discuss that castrated male mice had lower testosterone levels than male mice and that they recovered when testosterone was replaced. However, testosterone reduces the beneficial effects of ADT-induced memory impairment in these mice. ADT decreases testosterone and estradiol, which are necessary for maintaining normal brain function. Their research suggests that impaired angiogenesis in the hippocampus is increased in mice after combination astrocyte-endothelial cell co-cultured with testosterone by activating the p-ERK1/2/MAPK pathway and p-Foxo1. Thus, testosterone can reduce the effects of memory impairments in men undergoing prostate cancer treatments. The mechanism by which androgens reduce cognitive impairment also suggests that they reduce neurodegeneration in vulnerable areas such as the hippocampus.
A systematic review published in 2012 highlighted 14 studies led by Higano and Korean authors. The review aimed to investigate neurocognitive dysfunction in men with recurrent prostate cancer who underwent androgen-deprivation therapy and radiation therapy. All studies were of low to moderate quality and reported that androgen-deprivation therapy had detrimental effects on these patients. These effects included poorer working memory, decreased spatial memory, slower verbal and visual processing, greater difficulties with visual and verbal learning and long-term memory storage and retrieval, and slower psychomotor speed.
In 2016, several authors discussed gender-specific biology and the role of sex hormones in AD pathology in women. This included a 2001 study that examined the effects of menopause on the neuropathology of women who underwent early surgical menopause and long-term use of estrogen replacement therapy on the risk of AD. However, gender-specific risk factors for men have not been as widely discussed as they have been for women. Nevertheless, the development of androgen-deprivation therapy and the associated increased risks of developing cognitive impairment have prompted further investigation.
Hormonal Factors
The substantial independence and relative importance of nonhormonal risk factors suggest that genetic, environmental, or metabolic characteristics that are clearly abnormal should also be important. Nonetheless, sex differences in the risk of EA would be expected to follow from any physiological differences between men and women. It is interesting to note that EA occurring in women as a result of the aging process, rather than a familial disease with early onset, also is often thought to result from disturbances in estrogenic activity. Data from the NHEFS show the first evidence from a population-based prospective study that individual differences in one component of estrogenic activity might account for some of the gender differences in risk ratios for senile dementia and AD. To the extent that any age-related decline in testosterone production by the testes or the adrenal gland occurs in men, or that differences in free or total testosterone between men are also potentially AD-related. The finding that an early age of vasectomy was both the non-sexual factor most strongly related to the incidence of AD and that it was protective against the risk of death among men was unexpected. One can think of various mechanisms through which vasectomy might influence the incidence of AD. It is likely that the variety of conditions for which vasectomy appears to be protective, and the lack of knowledge about its mechanisms that currently characterize the field, will necessitate large-scale cohort studies in future, in order to address the question of gender-independent relationships between vasectomy and chronic disease occurrence.
Occupational Factors
Several individual types of work are linked to the risk of developing Alzheimer’s disease. Some individuals who head corporations experience occupying high occupational status and have a low risk of developing Alzheimer’s disease. Males retiring from non-managerial wage and salary jobs and from managerial and professional positions showed a decline in cognitive ability, but no significant difference in the decline in cognitive abilities between the two groups was discovered. Males in professional occupations engage in mental job demands because these men had comparatively high cognitive scores with adjusted time spent at work. These findings suggest that maintaining job skills for males in professional occupations may influence cognitive abilities in old age. Finally, individuals in lower occupational status have a higher risk of Alzheimer’s disease in relation to individuals in higher occupational status. For instance, males who were managers and professionals were nearly 17% more likely to exhibit more optimal levels of cognitive capacity while males with an unskilled job, with no school education, and with unauthorized work would have an increased risk of almost 20%.
Research into the connection between occupational factors and Alzheimer’s disease in men is emerging. Participating in cognitively stimulating work could be protective against Alzheimer’s disease. However, the type of work one is involved in may be important in regard to one’s risk for Alzheimer’s disease. Research in male-centered occupations, such as managers, base-level workers, and business-oriented males, has revealed that working conditions influence men’s abilities to maintain their cognitive abilities as they age. For example, workers in physically laborious jobs had lower years of schooling, decreased cognitive functioning, decreased social interactions, and longer years of sports participation compared to workers in a more sedentary occupation. Manual work is directly associated with poor functional status and accelerated cognitive decline. On the other hand, future planning skills were related to a higher occupational status.
Currently, there is no cure for AD; however, the intervention prior to the onset of full-blown AD is one of the most effective forms of treatment. There is no question that more effective therapeutic methods are sorely needed. These logistic regression analyses control for MMSE, age, education, ADL (IADL), and a single lipid or other non-lipid/particle concentrations. Certain lifestyle factors could be considered as possible preventive actions, which have possible translational power. Primary prevention plays a key role in the prevention of AD. It can help delay or prevent the start of symptoms of AD. It is important to be healthy and exercise regularly. There are studies suggesting that a diet similar to the Heart Healthy Diet, sleep and the adequate amount of physical exercises can reduce the risk of having AD and other dementia, stroke, heart disease, diabetes and some forms of cancer.
In conclusion, AD in men is a growing public health concern related to the increasing age structure of the population. It is crucial to offer every possible investigative attempt to halt progression or to prevent the disease. Consistent relationship between a particular term and subsequent cognitive declines could suggest a modifiable factor associated with Alzheimer’s disease. Replicating this study among other groups such as Native Americans, Asian Americans is necessary and to generalize these findings and utilize predictive measures for population-based dementia cases. Identifying factors which increase the likelihood for development of cognitive decline is useful for targeting powders for potential intervention or even for halving progression of AD. With that said, a caveat is necessary. These factors are changes for incident Alzheimer’s disease, the suggestion that decreasing the risk factors is followed by a decrease in Alzheimer’s disease cases needs verification in a cohort study of long duration.