Occupational Risk for Coronary Artery Disease in Shift Workers - A Systematic Review.

BACKGROUND: Coronary artery disease (CAD) prevention in shift workers (SWs) poses a significant challenge worldwide, as CAD remains a major cause of mortality and disability. In the past, SWs were found at higher risk of CAD than non-s SWs. Nevertheless, the pathogenic mechanism between shift work and CAD to date is unclear. This systematic review aims to enhance understanding of the risk of CAD occurrence in SWs. METHODS: A systematic literature review was conducted from January 2013 to December 2023. MEDLINE/Pubmed databases were used initially, and additional relevant studies were searched from references. Shift work was defined as any schedule outside traditional shifts, including the night shift. RESULTS: Fifteen pertinent papers were categorized into risk assessment or risk management. Findings demonstrated an increased risk of CAD among SWs compared to non-SWs, with an increased CAD risk observed for both shift work and night shift work. DISCUSSION: Duration-response associations indicate that greater shift exposure is linked to higher CAD risk. SWs incur an increased risk of CAD through the atherosclerotic process. As shift work duration increases as the risk of atherosclerosis is higher, workers demonstrate a higher prevalence and severity of coronary artery plaques. CONCLUSIONS: The evidence-based results underscore the increased risk of CAD in SWs and are sufficient for proposing guidelines aimed at reducing the risk of CAD in SWs and at managing people with CAD in return to work characterized by disrupted circadian rhythms.

Assessing and managing the rotating shiftwork risk in 24-hours hospital wards: An empirical multicenter study.

BACKGROUND: A growing body of literature has showed the need to minimize the impact of rotating shiftwork (RS) on health of shift-healthcare workers (HCWs). OBJECTIVE: The aims of the study were: 1) assessing the occupational risk associated with RS program in HCWs employed in 24 hours hospital wards 2) testing the feasibility of the questionnaire used. METHODS: The Rotating Shiftwork Questionnaire (RSQ) was implemented to assess the RS risk (RSR); the analysis was addressed to: 1) Sentinel events (SE) and 2) Risk factors (RF). The RSQ was administered to the specialist nursing coordinators in eighteen hospitals in Italy with the aim to evaluate the RSR index among nurses in 24 hours hospital wards. RESULTS: Eighteen structures participated in the multicenter study, of which 12 (66.7%) were public. Concerning the Rotating Shiftwork Risk index, there are the 78.8% of observations in the intermediate zone, with RSR scores ranging from 14.1 and 16 and in the high score area (RSR > 26) in which there are 4 observations equal to the 21.2% of the total. The multivariate analysis showed that the only significant variable associated with RF score was the macro-area (for Northern regionsbeta = -0.651; p = 0.008). CONCLUSIONS: RSQ has been shown a feasible and applicable tool to analyze the RSR in healthcare sector through the detection of quantitative data involving indicators of the risk. The questionnaire allowed to identify improvement actions targeted at minimizing specific critical issues through strategic interventions focused on organizational environment.

Occupational health surveillance of healthcare workers during COVID 19 pandemic: a narrative review.

BACKGROUND AND AIMS: Current literature has increasingly highlighted the risk of spreading the SARS-COV-2 infection in healthcare settings and showed the need for occupational health surveillance of HCWs during the current epidemiological emergency from COVID-19, as a preventive measure to minimize the spread of the infection. The purpose of this narrative review was to evaluate the literature and discover what the latest developments are about the management of the occupational health surveillance of healthcare workers (HCWs) during COVID-19 pandemic. METHODS: We searched for publications in MEDLINE, Pubmed and Google Scholar using selected keywords. Each article was reviewed and categorized into one or more of the following three categories based on its subject matter: early diagnosis of COVID-19 in HCWs, detection of worker susceptibility to severe COVID-19, medical examination of HCWs returning to work after COVID-19. RESULTS: Selected articles showed the RT-PCR test for Sars-CoV-2 as the gold standard to enable rapid identification of infected HCWs; an effective schedule of occupational health surveillance allows the identification of the susceptibility of the workers to severe Covid-19 and protect HCWs returning to work from the disease. CONCLUSIONS: The findings of the present narrative review show the need to strenghten the occupational health surveillance of HCWs during the current COVID-19 pandemic, with the aim not only to contain the spread of the infection in healthcare settings, but also to protect HCWs coming back to work after the disease.

Post-traumatic stress disorder symptoms in healthcare workers: a ten-year systematic review.

BACKGROUND AND AIMS: Healthcare workers (HCWs) employed in hospital settings frequently experience many occupational stressors leading to post-traumatic stress disorder (PTSD) symptoms. Literature has increasingly highlighted PTSD as a major issue that involves both staff and healthcare organizations; the consequences of PTSD may include medication errors and lower standards of care. The current COVID-19 pandemic poses the need for preventing PTSD in HCWs working closely with COVID-19 patients. The purpose of this systematic review was to analyze the latest developments in assessing and managing the occupational risk of PTSD symptoms in hospital HCWs. METHODS: We searched for publications in MEDLINE/Pubmed using selected keywords. Each article was reviewed and categorized into one or more of the following four categories based on its subject matter: risk assessment, risk management and occurrence rates. RESULTS: Our search resulted in a total of 32 publications that matched our inclusion criteria.  Increased years of service, older age, previous year exposure to violence, personality traits (i.e. neuroticism), history of mental disorders, being non-graduates, were found to be workers' pre-trauma factors predicting PTSD symptoms. CONCLUSIONS: The findings suggest the need to prioritize preventative interventions aimed to anticipate the effects of traumatic exposure by training HCWs in evidence based anticipatory methods of coping with stressful events. With regard to the current COVID-19 pandemic, we found evidence of the need to strength social support and training targeted at psychological skills of medical staff who treated COVID-19 patients.

Shift work sleep disorder and job stress in shift nurses: implications for preventive interventions.

BACKGROUND: A growing literature has revealed a relationship between shift-work, including night-shift, and the disturbance of sleep-wake cycle, leading to insomnia and/or increased daytime sleepiness in shift nurses; recent findings showed an association between shift work sleep disorders and distress, work accidents, decreased job performance and, consequently, lower quality of health service provision and lower standards of care. OBJECTIVES: To analyze across the gender how shift nurses experience shift work sleep disorders and job stress. METHODS: A cross-sectional study was performed following the STROBE Statement. The Italian version of the Job Content Questionnaire, the Bergen Insomnia Scale and the Epworth Sleepiness Scale were administered to the registered nurses employed in three Departments of General Practice and Elderly Care Medicine. RESULTS: No significant association was found between high job strain and insomnia and daytime sleepiness. Significantly more women than men experienced high job strain, insomnia and daytime sleepiness; among women the level of social support was significantly and negatively associated with insomnia and daytime sleepiness. CONCLUSIONS: The findings of this study suggest that interventions aimed to prevent shift work sleep disorder and job stress in shift-nurses should incorporate the assessment of social support across the gender. Moreover, longitudinal studies are required to evaluate the effectiveness of interventions targeted on social support to minimize the occurrence of insomnia and daytime sleepiness in shift nurses.

Preventing Shift Work Disorder in Shift Health-care Workers.

The occurrence of the shift work disorder (SWD) in health-care workers (HCWs) employed in 24/7 hospital wards is a major concern through the world. In accordance with literature, SWD is the most frequent work-related disturb in HCWs working on shift schedules including night shift. In agreement with the Luxembourg Declaration on workplace health promotion (WHP) in the European Union, a WHP program has been developed in a large Hospital, involving both individual-oriented and organizational-oriented measures, with the aim to prevent the occurrence of SWD in nurses working on shifts including night shift. The objective assessment of rotating shift work risk and the excessive sleepiness were detected before and after the implementation of the WHP program, by using the Rotating Shiftwork-questionnaire and the Epworth Sleepiness Scale. The findings of this study showed the effectiveness of the implemented WHP program in minimizing the impact of shift work on workers' health and in preventing the misalignment between sleep-wake rhythm and shift working.

Job stress and needlestick injuries in nurses: a retrospective observational study.

BACKGROUND: The prevention of needlestick injuries (NSIs) in nurses employed in Emergency Departments (EDs) represents a special issue for healthcare organizations globally. Stressful working conditions, lack of organizational arrangements and lack of supporting one another at work, may contribute to increase the risk of NSIs. METHODS: We conducted an observational study to analyze: 1) the effectiveness of organizational interventions to minimize the occurrence of NSIs in ED nurses; 2) to measure the impact of such interventions on the safety budget. RESULTS: The occurrence of NSIs detected after organizational level interventions was significantly lower than the occurrence observed previously such interventions (p<0,05). By results, cost saving from managing fewer NSIs than the previous period was found. CONCLUSION: The study shows that the proactive, integrated and comprehensive management of organizational features at workplace brings benefits to employees and reduces the burden of the occurrence of NSIs. As result of the reduced NSIs frequency, the overall costs for follow-up of injured workers were reduced. (www.actabiomedica.it).

Preliminary assessment of rotating shiftwork risk in a 24-hours metal industry.

BACKGROUND: Rotational shiftwork (RS) has been linked to increased risk for safety and health of shift workers, globally. A growing literature has revealed a trend toward increased accident and injury rates in shift workers than non-shift workers. AIMS: The present research was aimed: 1) to develop a methodological path for a preliminary objective assessment of occupational risk by RS in a metal industry 2) to detect the consequent effective interventions for moderating the RS risk. METHODS: A modified version of the Rotational Shiftwork Questionnaire was designed by a panel of experts, through a Delphi study; the questionnaire was used for a pilot study to assess the RS risk in a metal industry. RESULTS: The questionnaire was entitled Rotating Shiftwork Questionnaire-Industry (RSQ-I) and was made up of two sections: 1) Sentinel Events; 2) Risk Factors. The assessment of RS risk showed a medium level of risk in the studied metal industry. Organizational level interventions were detected for moderating the impact of RS-risk on workers' safety and health. CONCLUSION: RSQ-I showed a valid and reliable tool to analyze RS risk in a 24-hours metal industry. The pilot study demonstrated the effectiveness and feasibility of the introduced RSQ-I to approach the risk, through the analysis of both sentinel events and shift schedules.

Infectious risk in ostomy patient: the role of nursing competence.

BACKGROUND AND AIM OF THE WORK: The risk of peristomal infections in ostomy patients is well documented in the literature. The nurse and the stoma therapist play a fundamental role in the management and prevention of ostomy-related infections. The present research aims to investigate, across the different phases of the nursing process, the level and characteristics of nursing expertise and highlight their impact on reducing infectious risk in ostomy patients. METHODS: 40 nurses (31 women; mean age = 47.7; SD= 7.68) working with ostomy patients were interviewed, in three Italian Local Healthcare Company (LHC) of Northern Italy, Central Italy, and Southern Italy. Nurses compiled a semi-structured ad-hoc interview concerning the level of skills, training, and experience with ostomy patients. The declared expertise has been compared to the retrospective archive data related to the peristomal skin infections of the three LHC. RESULTS: Several differences have emerged in terms of nurses' expertise and care settings: for instance, ostomy complications in Southern Italy being managed with specific checklists, whereas in the Northern Italy complications being managed by stoma therapists and in Central Italy by hospital ward general nurses. Moreover, the level of professional training was very important for all respondents. The incidence rates of infections after training are lower than a pre-training period. CONCLUSIONS: The expertise resulting from specific training for nurses and stoma therapists are crucial for the management of the ostomy and the prevention of complications, in particular of infections. If the training reduces the peristomal complications, therefore, it is necessary to provide and preserve nurses' expertise, to guarantee patients an optimal treatment path.

Metabolic syndrome in shift healthcare workers.

BACKGROUND: Shift work including night shifts is generally associated with chronic misalignment between the endogenous circadian timing system and behavior cycles, leading to metabolic disorders including metabolic syndrome (MS). OBJECTIVES: The purpose of this research was to analyze the latest developments in assessing and managing the occupational risk of MS in shift-healthcare workers (HCWs). METHODS: According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, the authors used MEDLINE/Pubmed to perform a systematic review of literature from January 2008 to December 2018.  Results: Six studies were selected; the topics, discussed in order of frequency from highest to lowest, were: risk assessment, occurrence rates, and risk management. The main occupational determinants for MS were the cumulative shift work including night shifts and the number of nights worked per month per worker. With regard to cumulative lifetime exposure to shift work, the findings of our review suggest a dose-response relationship between increasing years of shift work history and MS in shift-HCWs. CONCLUSIONS: The findings suggest the need to better investigate the impact of sleep deprivation in the assessment of MS risk in shift-HCWs and clarify the role of such variables as confounders, mediators, or effect modifiers. Moreover, to date the data regarding management interventions focused on the risk of MS are inconsistent and therefore a special effort is required to detect strategic ways to minimize the likelihood of MS occurring in shift-HCWs.

Assessing and preventing low back pain in nurses. Implications for practice management.

BACKGROUND AND AIMS: The prevention of low back pain (LBP) among nurses employed in hospital departments represents a special concern for healthcare organizations globally. A growing literature evidences the need of workplace policy development related to organizational issues as strategic contribution to minimize the occurrence of LBP in healthcare sector. The purposes of this study were: 1) to analyze the relationship between shiftwork and acute LBP among female shift nurses; 2) to detect preventive interventions targeted on organizational issues. METHODS: The authors conducted a cross-sectional nested case-control analysis of data concerning acute LBP and staffing data for 671 nurses employed in the Departments of General Practice and Elderly Care Medicine. The statistical analysis consisted of a logistic regression to calculate incidence odds ratios with 95% confidence intervals. Chi-square test and t-test were used to examine the relationship between categorical and continuous data, respectively. RESULTS: The occurrence of acute LBP resulted significantly related to nightshift, extended shifts, obesity; the adoption of forward rotating schedules was found a protective factor in moderating the occupational risk of acute LBP in shift nurses. CONCLUSIONS: In this study the authors observed an association between shiftwork and acute LBP; improvement interventions should be aimed at: 1) moderating organizational risks linked with shiftwork schedules; 2) promoting healthy lifestyles. These interventions are suggested as a strategic way to effectively manage the phenomenon among female rotating shift nurses.

Gender assessment of job stress in healthcare workers. Implications for practice.

BACKGROUND: Work-related stress (WRS) in the healthcare sector is a major issue for both workers and organizations. To date, no consensus exists regarding differences in gender susceptibility to WRS in healthcare workers (HCWs). OBJECTIVES: The purpose of this study was to analyze how male and female HCWs employed in emergency departments experienced WRS. METHODS: A cross-sectional study was conducted regarding the perception of WRS in registered nurses employed in emergency departments. The Italian version of the Job Content Questionnaire and the Rapid Stress Assessment scale were administrated to 710 registered nurses. RESULTS: The WRS assessment showed that significantly more females than males were in a situation of isostrain (18.5% vs 9.8% p<0,05). In females, low social support was associated with high levels of job strain (18,5% vs 4,4% p<0,05). CONCLUSION: This study reflects the need for a gender-specific approach in the evaluation of WRS in the healthcare sector, and is consistent with literature that evidenced gender differences in the perception of WRS. Lack of social support proved to be a determinant of WRS in female HCWs. Organizational interventions aimed at providing a more suitable workgroup design are required in order to minimize WRS in female HCWs.

Workplace violence against healthcare workers in Emergency Departments. A case-control study.

BACKGROUND AND AIM: Assessment and management of workplace violence (WPV) towards healthcare workers (HCWs) employed in Emergency Departments (EDs) represents a challenge for healthcare organizations worldwide. To date there is a lack of scientific data about the impact of work-shifts on the occurrence of WPV against ED HCWs. The purpose of this study was to investigate the relationship between work shift schedules and WPV against registered nurses (RNs) working on non-traditional shifts, including nights and 12-hour shifts. METHODS: The authors conducted a cross-sectional nested case-control analysis of data regarding the episodes of WPV perpetrated by patients or their relatives against RNs employed in three EDs, in the period between January -December 2017. RESULTS: The one-year incidence of WPV was 29,30 per 100 Full Time Equivalent (FTE) positions. Cumulative nightshifts were significant for 3 or more nightshifts compared to working less than 3 nightshifts during the 7 days before the episodes of WPV; additionally, RNs working 9 or more night-shifts showed higher risk of experiencing WPV compared to RNs working less than 4 night-shifts in the previous 28 days. CONCLUSION: In the present study shift work and WPV occurrence against ED RNs resulted interconnected; improvement interventions aimed at preventing the WPV should consider the characteristics of work shift schedules with the purposes of: 1) limiting the night shifts up to two per week and up eight per month; 2) adopting constant forward-rotating shift schedules. (www.actabiomedica.it).

Preventing and managing workplace violence against healthcare workers in Emergency Departments.

BACKGROUND AND AIM: Healthcare workers (HCWs) employed in Emergency Departments (EDs) frequently face with patients becoming violent because of long wait or diseases or under the influence of alcohol or drugs. Globally, workplace violence (WPV) in EDs is a major challenge to safety for HCWs, involving significant consequences to the victims, patients, and healthcare organizations. We reviewed the current literature with the aim to explore the topics focused on and to detect new evidences about approaching the issue of WPV toward HCWs in EDs. METHODS: A search for articles regarding WPV toward HCWs employed in EDs and published from January 2007 through December 2017 was performed; using predetermined criteria for inclusion, selected articles were reviewed and qualitatively assessed for the aims of the review. RESULTS: We found 60 papers which matched our inclusion criteria; the topics, discussed in order of frequency from highest to lowest, were: "Risk Assessment", "Occurrence Rates", "Risk Management", and "Physical/non Physical Consequences". Dementia, schizophrenia, anxiety, acute stress reaction, suicidal ideation, and alcohol and drug intoxication were found as predictors of physical violence perpetrated by patients against HCWs. CONCLUSION: A strategic way to the effective management of WPV should prioritize training courses focused on: constructing HCW-patient relationship, improving the workers' communication skills, accurate reporting of each violent incident, and improving the labor context through management commitment and employee involvement in WPV prevention programs. A special effort is required in implementing workplace design effective in minimizing stressful conditions in waiting rooms which turned out to be the most frequent site of assaults.

Assessing and managing the shift work disorder in healthcare workers.

BACKGROUND: Shift work disorder (SWD) is a major concern for both healthcare workers (HCWs) employed in hospital wards and healthcare organizations. The consequences of SWD may lead to increased service costs and lower standards of care. OBJECTIVES: To identify and evaluate the latest developments in assessing and managing the occupational risk of SWD in shift-HCWs through a search of the literature published in the last five years. METHODS: We performed a search of the literature starting from June 2012, using MEDLINE/Pubmed. The articles were reviewed and categorized into one or more of the following categories based on their subject matter: Risk assessment, Risk management, Occurrence rates. RESULTS: A total of 25 publications matched the inclusion criteria. The topics discussed, in order of frequency (from the highest to the lowest), were: "Risk Assessment" (84%), "Occurrence Rates" (64%) and "Risk Management" (48%). Number of nights worked per year, long night-time working hours, frequent missing of nap opportunities during night-shift, quick returns and unhealthy workplace were found as organizational determinants of SWD that should be prioritized in the risk assessment of shift work in the healthcare sector. CONCLUSIONS: Organizational interventions targeted on both healthy shift-work scheduling and improvement of the workplace safety are proposed to moderate the occurrence of SWD and, consequently, to ensure HCWs' wellness and suitable standards of patient care. Further studies aimed to investigate the effectiveness of such interventions in minimizing SWD occurrence are needed.

Workplace Violence Toward Mental Healthcare Workers Employed in Psychiatric Wards.

BACKGROUND: Workplace violence (WPV) against healthcare workers (HCWs) employed in psychiatric inpatient wards is a serious occupational issue that involves both staff and patients; the consequences of WPV may include increased service costs and lower standards of care. The purpose of this review was to evaluate which topics have been focused on in the literature and which are new in approaching the concern of patient violence against HCWs employed in psychiatric inpatient wards, in the past 20 years. METHODS: We searched for publications in PubMed and Web of Science using selected keywords. Each article was reviewed and categorized into one or more of the following four categories based on its subject matter: risk assessment, risk management, occurrence rates, and physical/nonphysical consequences. RESULTS: Our search resulted in a total of 64 publications that matched our inclusion criteria. The topics discussed, in order of frequency (from highest to lowest), were as follows: "risk assessment," "risk management," "occurrence rates," and "physical/nonphysical consequences." Schizophrenia, young age, alcohol use, drug misuse, a history of violence, and hostile-dominant interpersonal styles were found to be the predictors of patients' violence. CONCLUSION: Risk assessment of violence by patients appeared the way to effectively minimize the occurrence of WPV and, consequently, to better protect mental HCWs. We found paucity of data regarding psychologic sequelae of WPV. According to these findings, we suggest the need to better investigate the psychologic consequences of WPV, with the aim of checking the effective interventions to assist HCW victims of violence and to prevent psychologic illness.

Depressive symptoms, vascular risk factors and mild cognitive impairment. The Italian longitudinal study on aging.

AIMS: We evaluated the impact of depressive symptoms on the rate of incident mild cognitive impairment (MCI) after a 3.5-year follow-up, and we assessed the interaction between depressive symptoms and vascular risk factors for incident MCI. METHODS: A total of 2,963 individuals from a sample of 5,632 65- to 84-year-old subjects were cognitively and functionally evaluated at the 1st and 2nd surveys of the Italian Longitudinal Study on Aging, a prospective cohort study with a 3.5-year follow-up. MCI and dementia were classified using current clinical criteria. Depressive symptoms were measured with the Geriatric Depression Scale. RESULTS: Among the 2,963 participants, 139 prevalent MCI cases were diagnosed at the 1st survey. During the 3.5-year follow-up, 105 new events of MCI were diagnosed. We did not observe any significant association between depressive symptoms and incident MCI (RR = 1.25, 95% CI = 0.85-1.84, chi(2) = 1.30, p < 0.25). No sociodemographic variables or vascular risk factors modified the relationship between depressive symptoms and incident MCI. CONCLUSION: In our population, depressive symptoms were not associated with the rate of incident MCI. Our findings did not support a role of sociodemographic variables or vascular risk factors in the link between depressive symptoms and incident MCI.

Cerebrovascular disease in the elderly: lipoprotein metabolism and cognitive decline.

Data concerning the treatment of lipoprotein disturbances in patients with cerebrovascular disease (CVD) are less robust than those for coronary heart disease (CHD), raising clinical questions as to which is the appropriate therapeutic approach to stroke patients. Although observational cohort studies have failed to demonstrate an association between lipoprotein disorders and stroke incidence, recently completed trials of subjects at risk for CHD have shown that statins reduce not only the risk of myocardial infarction and death, but also that of brain infarction and transient ischemic attacks. At present, it seems reasonable to conclude that stroke patients with undesirable lipid profiles who have a history of CHD should receive specific treatment for the lipid disorder. Recommendations are more problematic for stroke patients with lipid disorder but no history of CHD. Furthermore, many of the risk factors for CVD and vascular dementia (VaD), including serum total cholesterol (TC), lipoprotein(a), diabetes, atrial fibrillation, hypertension, apolipoprotein E levels, and atherosclerosis, have also been shown to increase the risk of Alzheimer's disease (AD). In a recent study, we estimated the prevalence, incidence and rate of progression of Mild Cognitive Impairment (MCI) to dementia, and correlated vascular risk factors with incident MCI and its progression to dementia. We evaluated 2963 individuals from the population-based sample of 5632 subjects 65-84 years old of the Italian Longitudinal Study on Aging, with a 3.5-year follow-up. We found a progression rate to dementia (all causes) of 3.8/100 person-years. Furthermore, age was a risk factor for incident MCI, while education was protective, and serum TC evidenced a non-significant borderline trend for a protective effect. There was a non-significant trend for stroke as a risk factor of progression of MCI to dementia. In conclusion, in our population, among MCI patients who progressed to dementia, 60% progressed to AD and 33% to VaD. Vascular risk factors and CVD may influence the development of MCI and the rate of progression to dementia.

Circulating biomarkers of cognitive decline and dementia.

Plasma and serum biochemical markers proposed for cognitive decline of degenerative (Alzheimer's disease, AD) or vascular origin and predementia syndromes (mild cognitive impairment and other related entities) are based on pathophysiologic processes such as lipoprotein metabolism (total cholesterol, apolipoprotein E, 24S-hydroxy-cholesterol), and vascular disease (homocysteine, lipoprotein(a)); SP formation (amyloid beta(Abeta)-protein, Abeta autoantibodies, platelet APP isoforms), oxidative stress (isoprostanes, vitamin E), and inflammation (cytokines). This review will focus on the current knowledge on circulating serum and plasma biomarkers of cognitive decline and dementia that are linked to cholesterol homeostasis and lipoprotein abnormalities, senile plaque formation and amyloid precursor protein (APP) metabolism, oxidative stress, and inflammatory reactions. Special emphasis will, however, be placed on biomarkers related to lipoprotein metabolism and vascular disease. Analytically, most plasma and serum proteins or metabolites lack reproducibility, sensitivity, or specificity for the diagnosis, risk and progression assessment, or therapeutic monitoring of AD and other dementing disorders. Measures linked to lipoprotein metabolism and vascular disease, APP metabolism, oxidative stress, or inflammation appear altered in AD relative to controls, but lack sufficient discriminatory power. Measures combining several biomarkers or incorporating a range of proteins in plasma and small molecule metabolites are promising approaches for the development of plasma or serum-based diagnostic tests for AD and other dementing disorders, as well as for predementia syndromes.