An ELOVL2-Based Epigenetic Clock for Forensic Age Prediction: A Systematic Review.

The prediction of chronological age from methylation-based biomarkers represents one of the most promising applications in the field of forensic sciences. Age-prediction models developed so far are not easily applicable for forensic caseworkers. Among the several attempts to pursue this objective, the formulation of single-locus models might represent a good strategy. The present work aimed to develop an accurate single-locus model for age prediction exploiting ELOVL2, a gene for which epigenetic alterations are most highly correlated with age. We carried out a systematic review of different published pyrosequencing datasets in which methylation of the ELOVL2 promoter was analysed to formulate age prediction models. Nine of these, with available datasets involving 2298 participants, were selected. We found that irrespective of which model was adopted, a very strong relationship between ELOVL2 methylation levels and age exists. In particular, the model giving the best age-prediction accuracy was the gradient boosting regressor with a prediction error of about 5.5 years. The findings reported here strongly support the use of ELOVL2 for the formulation of a single-locus epigenetic model, but the inclusion of additional, non-redundant markers is a fundamental requirement to apply a molecular model to forensic applications with more robust results.

The intention to get COVID-19 vaccine and vaccine uptake among cancer patients: An extension of the theory of planned behaviour (TPB).

The psychosocial impact of coronavirus disease 2019 (COVID-19) on human life is well-known. Although vaccine protection represents an effective way to control the spread of the virus, vaccination hesitancy may decrease individuals' willingness to get vaccinated, including among cancer patients. Therefore, the objective of the current study was to examine the predictors of cancer patients' intentions to receive COVID-19 vaccinations and vaccine uptake, using and integrating the theory of planned behaviour (TPB) and the health belief model (HBM). A sample of 276 Italian cancer patients (54% female and 46% male) ranging from 19 to 85 years (M = 49.64, SD = 11.53) was recruited by administering an online questionnaire. The current study results showed that cancer patients with higher trust in health authorities tended to have vaccine-positive subjective norms, perceived that vaccination was under their control, and viewed COVID-19 vaccines positively. On the other hand, the perceived risk of COVID-19 was related to subjective norms but not to perceived behavioural control or attitudes towards COVID-19 vaccination. The current study reveals that TPB variables can function effectively as mediators between perceived risk, trust, and intention to vaccinate but at different levels. Together, these findings suggest that effective interventions (both public health messaging and personal medical communications) should focus on enhancing trust in health authorities, while at the same time endeavouring to highlight subjective norms that are vaccine-positive.

The longitudinal association between Perceived Stress, PTSD Symptoms, and Post-Traumatic Growth during the COVID-19 Pandemic: the role of coping strategies and psychological inflexibility.

The present study investigates the mediating roles of psychological inflexibility and differential coping strategies on perceived stress and post-traumatic symptoms and growth in the context of COVID-19. Study one recruited 662 participants (54.8% women; Mage = 40.64 years, SD = 13.04) who completed a cross-sectional questionnaire. It was proposed that orientation to the problem, avoidance strategies, psychological inflexibility, and positive attitude were mediators for the positive association between perceived stress and PTSD symptoms. The fit indices for the path model were excellent: CFI = 0.977, TLI = 0.950, RMSEA = 0.057 [90%CI = 0.043-0.081], and SRMS = 0.042. Gender and stressful events encountered had indirect effects on the endogenous variables. In study two, 128 participants (57.8% women; Mage = 42.30, SD = 12.08) were assessed for post-traumatic growth one year later. Psychological inflexibility and orientation acted as mediators between perceived stress and PTSD symptoms. Furthermore, a novel path model was constructed in which psychological inflexibility and orientation to the problem as mediators for perceived stress and PTSD symptoms. The indices for the path model were excellent: CFI = 0.99, TLI = 0.97, RMSEA = 0.055 [90%CI = 0.001-0.144], and SRMS = 0.49. Furthermore, PTSD symptoms, psychological inflexibility, and orientation to the problem predicted post-traumatic growth. Specifically, both orientation to the problem (ß = .06 [90%CI: .01;.13]) and psychological inflexibility (ß = .14 [90%CI: .08;.26]) had an indirect effect on post-traumatic growth. Overall, these results significantly contribute to the literature as orientation to the problem positively predicted PTSD symptoms and post-traumatic growth one year later while psychological inflexibility predicted PTSD symptoms and less post-traumatic growth one year later. These results underline the importance of assessing both symptomology and psychological growth to determine adaptive coping strategies in specific contexts.

Understanding the longitudinal associations between e-cigarette use and general mental health, social dysfunction and anhedonia, depression and anxiety, and loss of confidence in a sample from the UK: A linear mixed effect examination.

OBJECTIVE: Our objective was to the longitudinal associations between e-cigarette use and general mental health, social dysfunction & anhedonia, depression & anxiety, and loss of confidence in a sample from the UK. METHODS: We analyzed data of 19,706 participants from Wave 9 (collected from 2017 to 2018) and Wave 10 (collected from 2018 to 2019) of the Understanding Society: the UK Household Longitudinal Study using a confirmatory factor analysis, linear mixed effect model, and one-sample t-tests. RESULTS: We found that there is a significant time by e-cigarette use status interaction on mental health issues (b = 0.32, p < 0.001, 95 % C.I. [0.15, 0.49]), social dysfunction & anhedonia (b = 0.36, p < 0.001, 95 % C.I. [0.18, 0.54]), and loss of confidence (b = 0.24, p < 0.01, 95 % C.I. [0.06, 0.41]). Indeed, participants who became e-cigarette smokers at Wave 10 had worse mental health (t(107) = 2.64, p < 0.01, 95 % C.I. [0.07, 0.48], Cohen's d = 0.28), social dysfunction & anhedonia (t(107) = 3.16, p < 0.01, 95 % C.I. [0.12, 0.52], Cohen's d = 0.32), and loss of confidence (t(107) = 2.08, p < 0.05, 95 % C.I. [0.01, 0.37], Cohen's d = 0.19) comparing to one year ago. LIMITATION: Limitations of this study included its self-report measures, unclassified e-cigarette type, limited generalizability to other populations, and lack of experimental manipulations. CONCLUSION: We revealed longitudinal associations between e-cigarette initiation and adverse general and dimensions of mental health except for depression and anxiety, which have significant implications for public health, specifically in terms of e-cigarette product regulation and advertising.

Unraveling sex differences in Parkinson's disease through explainable machine learning.

Sex differences affect Parkinson's disease (PD) development and manifestation. Yet, current PD identification and treatments underuse these distinctions. Sex-focused PD literature often prioritizes prevalence rates over feature importance analysis. However, underlying aspects could make a feature significant for predicting PD, despite its score. Interactions between features require consideration, as do distinctions between scoring disparities and actual feature importance. For instance, a higher score in males for a certain feature doesn't necessarily mean it's less important for characterizing PD in females. This article proposes an explainable Machine Learning (ML) model to elucidate these underlying factors, emphasizing the importance of features. This insight could be critical for personalized medicine, suggesting the need to tailor data collection and analysis for males and females. The model identifies sex-specific differences in PD, aiding in predicting outcomes as "Healthy" or "Pathological". It adopts a system-level approach, integrating heterogeneous data - clinical, imaging, genetics, and demographics - to study new biomarkers for diagnosis. The explainable ML approach aids non-ML experts in understanding model decisions, fostering trust and facilitating interpretation of complex ML outcomes, thus enhancing usability and translational research. The ML model identifies muscle rigidity, autonomic and cognitive assessments, and family history as key contributors to PD diagnosis, with sex differences noted. The genetic variant SNCA-rs356181 may be more significant in characterizing PD in males. Interaction analysis reveals a greater occurrence of feature interplay among males compared to females. These disparities offer insights into PD pathophysiology and could guide the development of sex-specific diagnostic and therapeutic approaches.

Genetic variability of FOXP2 and its targets CNTNAP2 and PRNP in frontotemporal dementia: A pilot study in a southern Italian population.

The Forkhead box P2 (FOXP2) is an evolutionary conserved transcription factor involved in the maintenance of neuronal networks, implicated in language disorders. Some evidence suggests a possible link between FOXP2 genetic variability and frontotemporal dementia (FTD) pathology and related endophenotypes. To shed light on this issue, we analysed the association between single-nucleotide polymorphisms (SNPs) in FOXP2 and FTD in 113 patients and 223 healthy controls. In addition, we investigated SNPs in two putative targets of FOXP2, CNTNAP2, Contactin-associated protein-like 2 and PRNP, prion protein genes. Overall, 27 SNPs were selected by a tagging approach. FOXP2-rs17213159-C/T resulted associated with disease risk (OR = 2.16, P = 0.0004), as well as with age at onset and severity of dementia. Other FOXP2 markers were associated with semantic and phonological fluency scores, cognitive levels (MMSE) and neuropsychological tests. Associations with language, cognitive and brain atrophy measures were found with CNTNAP2 and PRNP genetic variability. Overall, although preliminary, results here presented suggest an influence of regulatory pathways centred on FOXP2 as a molecular background of FTD affecting neurological function of multiple brain areas.

Understanding Cognitive Deficits in People with Coronary Heart Disease (CHD).

Coronary heart disease (CHD) is one of the main cardiovascular diseases that can cause disability and death across the globe. Although previous research explored the links between CHD and cognitive deficits, only a subset of cognitive abilities was analyzed and a small clinical sample size was used. Thus, the aim of the current study is to assess how CHD can affect the cognitive domains of episodic memory, semantic verbal fluency, fluid reasoning, and numerical ability in a large cohort of participants from the United Kingdom. Results revealed that episodic memory, semantic verbal fluency, fluid reasoning, and numerical ability are negatively affected by CHD. Prevention and intervention should be developed to preserve cognitive abilities in people with CHD, but more studies should explore specific ways of doing so.

Self-rated health (SRH) partially mediates and associations between personality traits and life satisfaction in older adults.

It is established that personality traits contribute to life satisfaction but why they are connected are far less understood. This research report tested if self-rated health (SRH) which is one's subjective ratings of their health and has a high predictivity of actual health mediates the associations between the Big Five model of personality and life satisfaction in a cohort (N = 5,845) of older adults from the UK. By using Pearson's correlation analysis and mediation analysis, the current research reported positive correlations between Agreeableness, Openness, Conscientiousness, and Extraversion, SRH, and life satisfaction. However, Neuroticism was negatively correlated with SRH and life satisfaction. The main findings were that SRH partially mediates the associations between all traits in the Big Five and life satisfaction in older adults. This study began novel exploration on if SRH could explain the connections between the Big Five and life satisfaction. Results revealed SRH could partially explain these associations in all traits. These results may offer additional support to recently developed integrated account of life satisfaction, which argues that there are no single determinants of life satisfaction. Rather, life satisfaction is made up by many factors including but not limited to personality and health.

Mental Health in Coronary Heart Disease (CHD) Patients: Findings from the UK Household Longitudinal Study (UKHLS).

OBJECTIVES: Mental health conditions in patients with coronary heart disease (CHD) are closely related to clinical outcomes. Thus, this study's goal is to investigate how CHD affects general and specific aspects of mental health. METHODS: We analyzed data from Wave 10 Understanding Society: the UK Household Longitudinal Study (UKHLS), which were collected between 2018 and 2019. After removing people who had missing data, there were 450 participants who indicated that they have CHD, and 6138 age- and sex-matched healthy participants indicated that they were not clinically diagnosed with CHD. RESULTS: The main findings were that participants with CHD had more mental health problems, as shown by the GHQ-12 summary score (t (449) = 6.00, p < 0.001, 95% C.I. [0.20, 0.40], Cohen's d = 0.30), social dysfunction and anhedonia, (t (449) = 5.79, p < 0.001, 95% C.I. [0.20, 0.40], Cohen's d = 0.30), depression and anxiety (t (449) = 5.04, p < 0.001, 95% C.I. [0.15, 0.33], Cohen's d = 0.24), and loss of confidence (t (449) = 4.46, p < 0.001, 95% C.I. [0.11, 0.30], Cohen's d = 0.21). CONCLUSION: This study implies that GHQ-12 is a valid assessment of mental health problems in CHD patients, and there is a need to consider how different aspects of mental health are affected by CHD rather than solely focusing on depression or anxiety problems alone in patients with CHD.

Personality Traits Predict Self-Rated Health (SRH) in Coronary Heart Disease (CHD) Patients and Healthy Controls.

OBJECTIVE: The objective of the present study is to examine the association between Big Five personality traits and self-rated health (SRH) among individuals with coronary heart disease (CHD), and to compare this relationship with that of healthy control participants, which is of importance as SRH can be a determinant of outcomes. METHODS: The current study used data from 566 participants with CHD with a mean age of 63.00 (S.D. = 15.23) years old (61.13% males) and 8608 age- and sex-matched healthy controls with a mean age of 63.87 (S.D.= 9.60) years old (61.93% males) from the UKHLS. The current study used predictive normative modelling approaches, one-sample t tests, a hierarchical regression, and two multiple regressions. RESULTS: The current study found that CHD patients have significantly lower Conscientiousness (t(565) = -3.84, p < 0.001, 95% C.I. [-0.28, -0.09], Cohen's d = -0.16) and SRH (t(565) = -13.83, p < 0.001, 95% C.I. [-0.68, -0.51], and Cohen's d = -0.58) scores compared to age and sex-matched healthy controls. Moreover, health status (controls vs. CHD patients) moderated the links between Neuroticism, Extraversion and SRH. Specifically, Neuroticism (b = -0.03, p < 0.01, 95% C.I. [-0.04, -0.01]), Openness (b = 0.04, p < 0.001, 95% C.I. [0.02, 0.06]), and Conscientiousness (b = 0.08, p < 0.001, 95% C.I. [0.06, 0.10]) were significant predictors of SRH in healthy controls, whereas Conscientiousness (b = 0.08, p < 0.05, 95% C.I. [0.01, 0.16]) and Extraversion (b = -0.09, p < 0.01, 95% C.I. [-0.15, -0.02]) were significant predictors of SRH in CHD patients. CONCLUSION: Based on the close associations between personality traits and SRH, and the subsequent impact on patient outcomes, the results of this study should be taken into consideration by clinicians and health professionals when developing tailored treatment and intervention programs for their patients.

Associations between Personality Traits and Areas of Job Satisfaction: Pay, Work Itself, Security, and Hours Worked.

Although studies have widely explored the connections between personality traits and job satisfaction, less is known about how personality relates to aspects of job satisfaction. The objective of this study was to explore the relationships between personality traits and various areas of job satisfaction, including pay, work, security, and hours worked. This study used ordinal regressions to analyze data from 6962 working individuals from the British Household Panel Survey (BHPS). The results showed that Neuroticism consistently has a negative association with all aspects of job satisfaction, whereas Agreeableness and Conscientiousness have positive associations with job satisfaction. Extraversion had a weak negative association with satisfaction with total pay. These findings imply that personality may play a crucial role in shaping areas of job satisfaction.

Can the Big Five personality traits predict ever chance and 7-year risk of clinically diagnosed chronic bronchitis in middle-aged and older adults?

OBJECTIVE: Chronic bronchitis refers to a chronic condition that is characterized by long-term inflammation of the bronchi. It is of great importance to understand the contributing risk factors for chronic bronchitis because it is associated with adverse outcomes such as healthcare burden and mortality. We aimed to understand if the personality traits could predict ever and the 7-year risk of clinically diagnosed chronic bronchitis in a large cohort of participants from the UK. METHODS: We analyzed data from Understanding Society: the UK Household Longitudinal Study, which consists of 15,387 middle-aged or older participants for the cross-sectional analysis and 8783 middle-aged or older adults for the longitudinal analysis using two binary logistic regressions. RESULTS: We found that Neuroticism (OR = 1.36, p < 0.001, 95% C.I. [1.23, 1.51]), Conscientiousness (OR = 0.87, p = 0.014, 95% C.I. [0.78, 0.97]), and Extraversion (OR = 1.15, p = 0.009, 95% C.I. [1.04, 1.29]) are related to a higher chance of ever clinically diagnosed chronic bronchitis. However, Agreeableness and Openness were not related to the chance of ever clinically diagnosed chronic bronchitis. Moreover, Conscientiousness (OR = 0.72, p = 0.012, 95% C.I. [0.55, 0.93]) was related to a lower risk of future clinical diagnosis of chronic bronchitis whereas Extraversion (OR = 1.35, p = 0.024, 95% C.I. [1.04, 1.76]) was associated with a higher risk of future chronic bronchitis. However, Neuroticism, Agreeableness, and Openness were not related to change of ever clinically diagnosed chronic bronchitis. CONCLUSION: We showed that personality can identify people who are at greater risk of chronic bronchitis, which has translational utility for healthcare of middle-aged and older adults.

People with Diabetes Have Poorer Self-Rated Health (SRH) and Diabetes Moderates the Association between Age and SRH.

Diabetes is a severe chronic condition that is related to decreased physical functioning. Recently, there has been growing interest in understanding how a brief report on health such as self-rated health (SRH) could be used to track changes in health status and service needs in people with diabetes. The current research aims to investigate how SRH is affected by diabetes and how diabetes could moderate the association between age and SRH. By analyzing data from 47,507 participants, with 2869 of them clinically diagnosed with diabetes, the current study found that people with diabetes had significantly poorer SRH than people without diabetes after controlling for demographic covariates (t(2868) = -45.73, p < 0.001, 95% C.I. (-0.92, -0.85), Cohen's d = -0.85). In addition, diabetes was a significant moderator of the relationship between age and SRH (b = 0.01, p < 0.001, 95% C.I. (0.01, 0.01)). Specifically, age was more strongly related to SRH in people without diabetes (b = -0.015, p < 0.001, 95% C.I. (-0.016, -0.015)) than in people with diabetes (b = -0.007, p < 0.001, 95% C.I. (-0.010, -0.004)). Health professionals should aim to improve SRH in people with diabetes given that SRH is related to various outcomes.

Understanding the Role of Cancer Diagnosis in the Associations between Personality and Life Satisfaction.

Life satisfaction refers to the degree a person enjoys their life. An integrated account of life satisfaction is discussed in the literature, which proposes that life satisfaction is made up of personality traits and areas of life satisfaction (e.g., satisfaction with health, job, and social life). In addition, disruptions in one domain (e.g., health) may disrupt the association between personality traits and life satisfaction. The current research was interested in if clinically diagnosed cancer could influence the association between the Big Five personality traits and life satisfaction. The current study analyzed data from 1214 people with a diagnosis of cancer (38.55% males) with an average age of 59.70 (S.D. = 15.53) years and 13,319 people without a cancer diagnosis (38.13% males) with an average age of 59.97 (S.D. = 11.10) years who participated in Understanding Society: the UK Household Longitudinal Study (UKHLS). For the first time, our study revealed that cancer markedly influences the relationship between Agreeableness and life satisfaction, after accounting for demographic variables. Neuroticism was negatively associated with life satisfaction in people with and without clinically diagnosed cancer, whereas Agreeableness and Extraversion were positively associated with life satisfaction in people with and without clinically diagnosed cancer. Openness and Conscientiousness were positively related to life satisfaction in people without cancer but were not significant predictors in people with cancer. Health professionals should develop strategies and interventions by fostering personality traits, including Agreeableness, Openness, Conscientiousness, and Extraversion, while reducing Neuroticism.

Understanding Cognitive Deficits in People with Arthritis.

Cognitive deficits are commonly seen in people with arthritis. However, previous studies focused primarily on small-sized clinical samples. There is a need for cohort-based studies, which are characterized by high generalizability. In addition, these studies mainly focused on attention, memory, and executive function. However, cognition is not a single concept, but includes other cognitive domains, such as verbal fluency and arithmetic abilities. Thus, we aim to explore how arthritis can affect cognitive abilities, including episodic memory, semantic verbal fluency, fluid reasoning, and numerical ability by using a large cohort from the United Kingdom. The main findings were that people with arthritis have significantly lower immediate word recall (t(2257) = -6.40, p < 0.001, Cohen's d = -0.12, 95% C.I. = [-0.16, -0.08]), delayed word recall (t(2257) = -5.60, p < 0.001, Cohen's d = -0.11, 95% C.I. = [-0.14, -0.07]), semantic verbal fluency (t(2257) = -3.03, p < 0.01, Cohen's d = -0.06, 95% C.I. = [-0.10, -0.02]), fluid reasoning (t(2257) = -3.96, p < 0.001, Cohen's d = -0.07, 95% C.I. = [-0.11, -0.04]), and numerical ability (t(2257) = -3.85, p < 0.001, Cohen's d = -0.07, 95% C.I. = [-0.10, -0.03]) compared to what they would expect given their demographics. Interventions are needed to improve cognitive abilities in people with arthritis.

Asthma Moderates the Association between the Big Five Personality Traits and Life Satisfaction.

The current study aimed to examine whether asthma moderates the association between the Big Five personality traits and life satisfaction. By analyzing data from 3934 people with asthma (40.09% males) with a mean age of 49.2 (S.D. = 16.94) years old and 22,914 people without asthma (42.9% males) with a mean age of 45.62 (S.D. = 17.25) years old using a hierarchical regression and multiple regressions, the current study found that asthma significantly moderates the link between Neuroticism and life satisfaction and Openness and life satisfaction after controlling for other covariates. Specifically, Neuroticism was negatively related to life satisfaction whereas Agreeableness, Openness, Conscientiousness, and Extraversion were positively associated with life satisfaction in people with and without asthma. However, the negative association between Neuroticism and life satisfaction and the positive association between Openness and life satisfaction were stronger in people with asthma compared to people without asthma.

Big Five personality traits in the workplace: Investigating personality differences between employees, supervisors, managers, and entrepreneurs.

Personality relates to employment status. Previous studies have mainly compared the difference between entrepreneurs and managers. It remains unknown how personalities differ in entrepreneurs, managers, supervisors, and employees. In this research, we answer the questions by analyzing data from Understanding Society: the UK Household Longitudinal Study (UKHLS) that consisted of 2,415 entrepreneurs, 3,822 managers, 2,446 supervisors, and 10,897 employees. By using a multivariate analysis of variance (MANOVA) and ANOVA, we found that employment status has a significant multivariate effect on personality traits (F(5, 17,159) = 172.51, p < 0.001) after taking account into demographics. Moreover, there were also significant univariate effects for Neuroticism (F(3,19502) = 16.61, P < 0.001), Openness (F(3,19502) = 3.53, P < 0.05), Agreeableness (F(3,19502) = 66.57, P < 0.001), Conscientiousness (F(3,19502) = 16.39, P < 0.001), and Extraversion (F(3,19502) = 31.61, P < 0.001) after controlling for demographics. Multiple comparisons revealed that entrepreneurs are characterized by low Neuroticism, high Openness, high Conscientiousness, and high Extraversion while managers had low Neuroticism, low Agreeableness, high Openness, high Conscientiousness, and high Extraversion. Finally, supervisors are associated with high Conscientiousness. Implications and limitations are discussed.

Personality traits and dimensions of mental health.

Individuals are different in a relatively constant pattern of thoughts, feeling, and behaviors, which are called personality traits. Mental health is a condition of well-being in which people may reach their full potential and deal effectively with stress, work efficiently, and contribute to their communities. Indeed, the link between personality and mental health as indicated by the 12-item version of the general health questionnaires (GHQ-12) has been well-established according to evidence found by decades of research. However, the GHQ-12 comprises many questions asking about different dimensions of mental health. It is unclear how personality traits relate to these dimensions of mental health. In this paper, we try to address this question. We analyzed data from 12,007 participants from the British Household Panel Study (BHPS) using a confirmatory factor analysis (CFA) and generalized linear models. We replicated the factor structure of GHQ-12 labeled as GHQ-12A (social dysfunction & anhedonia; 6 items), GHQ-12B (depression & anxiety; 4 items), and GHQ-12C (loss of confidence; 2 items). Moreover, Neuroticism was positively related to all dimensions of mental health issues, Extraversion was negatively related to GHQ-12A (social dysfunction & anhedonia) and GHQ-12B (depression & anxiety), Agreeableness and Conscientiousness were negatively related to GHQ-12A (social dysfunction & anhedonia) and GHQ-12C (loss of confidence), and Openness was negatively related to GHQ-12B (depression & anxiety). These results contribute to theories including the predisposition/vulnerability model, complication/scar model, pathoplasty/exacerbation model, and the spectrum model, which propose that personality traits are linked to mental health and explained possible reasons. Psychologists may use results from this study to identify individuals who may be at high risk of developing various non-psychiatric mental health issues and intervene to avoid negative outcomes.

Microglial Senescence and Activation in Healthy Aging and Alzheimer's Disease: Systematic Review and Neuropathological Scoring.

The greatest risk factor for neurodegeneration is the aging of the multiple cell types of human CNS, among which microglia are important because they are the "sentinels" of internal and external perturbations and have long lifespans. We aim to emphasize microglial signatures in physiologic brain aging and Alzheimer's disease (AD). A systematic literature search of all published articles about microglial senescence in human healthy aging and AD was performed, searching for PubMed and Scopus online databases. Among 1947 articles screened, a total of 289 articles were assessed for full-text eligibility. Microglial transcriptomic, phenotypic, and neuropathological profiles were analyzed comprising healthy aging and AD. Our review highlights that studies on animal models only partially clarify what happens in humans. Human and mice microglia are hugely heterogeneous. Like a two-sided coin, microglia can be protective or harmful, depending on the context. Brain health depends upon a balance between the actions and reactions of microglia maintaining brain homeostasis in cooperation with other cell types (especially astrocytes and oligodendrocytes). During aging, accumulating oxidative stress and mitochondrial dysfunction weaken microglia leading to dystrophic/senescent, otherwise over-reactive, phenotype-enhancing neurodegenerative phenomena. Microglia are crucial for managing Aß, pTAU, and damaged synapses, being pivotal in AD pathogenesis.