Lack of Immune Resilience Negatively Affects Physical Resilience: Results From the InCHIANTI Follow-Up Study.

There is consistent evidence that immune response declines with aging, with wide interindividual variability and a still unclear relationship with the development of frailty. To address this question, we assessed the role of immune resilience (capacity to restore immune functions), operationalized as the neutrophil-to-lymphocytes ratio (NL-ratio) and monocytes-to-lymphocytes ratio (ML-ratio), in the pathway that from robust status shifts to pre-frailty and frailty, and finally to death. The InCHIANTI study enrolled representative samples from the registry lists of 2 towns in Tuscany, Italy. Baseline data were collected in 1998, with follow-up visits every 3 years. The 1 453 participants enrolled were assessed and followed for lifestyle, clinical condition, physical performance, clinical, and physiological measures. For the purpose of this analysis, we used only 1 022 subjects aged 65 or older at baseline. Participants in the 3 highest deciles of distribution for NL-ratio (>2.44) were more likely to experience a transition from robust to pre-frail, and to overt frailty status. Moreover, NL-ratio (tenth decile > 3.53) and ML-ratio (tenth decile > 2.02) were both predictors of mortality. These results were independent of chronological age, sex, comorbidities, and chronic low-grade inflammation assessed by high sensitivity C-reactive protein measurement. The 2 leucocytes-derived ratios, NL-ratio and ML-ratio, represent markers of immune resilience and predict changes in physical resilience and mortality. These biomarkers are inexpensive because they are based on data routinely collected in clinical practice and can be used to assess the risk of frailty progression and mortality. Clinical Trials Registration Number: NCT01331512.

Bone Mineral Density and Trabecular Bone Score Changes throughout Menopause in Women with HIV.

OBJECTIVE: The objectives of this study were to describe the trajectories of bone mineral density (BMD) and trabecular bone score (TBS) changes throughout pre-menopause (reproductive phase and menopausal transition) and post-menopause (early and late menopause) in women with HIV (WWH) undergoing different antiretroviral therapies (ARTs) and explore the risk factors associated with those changes. METHODS: This was an observational longitudinal retrospective study in WWH with a minimum of two DEXA evaluations comprising BMD and TBS measurements, both in the pre-menopausal and post-menopausal periods. Menopause was determined according to the STRAW+10 criteria, comprising four periods: the reproductive period, menopausal transition, and early- and late-menopausal periods. Mixed-effects models were fitted to estimate the trajectories of the two outcomes (BMD and TBS) over time. Annualized lumbar BMD and TBS absolute and percentage changes were calculated in each STRAW+10 time window. A backward elimination procedure was applied to obtain the final model, including the predictors that affected the trajectories of BMD or TBS over time. RESULTS: A total of 202 WWH, all Caucasian, were included. In detail, 1954 BMD and 195 TBS data were analyzed. The median number of DEXA evaluations per woman was 10 (IQR: 7, 12). The median observation periods per patient were 12.0 years (IQR = 8.9-14.4) for BMD and 6.0 years (IQR: 4.3, 7.9) for TBS. The prevalence of osteopenia (63% vs. 76%; p < 0.001) and osteoporosis (16% vs. 36%; p < 0.001) increased significantly between the pre-menopausal and post-menopausal periods. Both BMD (1.03 (±0.14) vs. 0.92 (±0.12) g/cm2; p < 0.001) and TBS (1.41 (IQR: 1.35, 1.45) vs. 1.32 (IQR: 1.28, 1.39); p < 0.001) decreased significantly between the two periods. The trend in BMD decreased across the four STRAW+10 periods, with a slight attenuation only in the late-menopausal period when compared with the other intervals. The TBS slope did not significantly change throughout menopause. The delta mean values of TBS in WWH were lower between the menopausal transition and reproductive period compared with the difference between menopause and menopausal transition. CONCLUSIONS: Both BMD and TBS significantly decreased over time. The slope of the change in BMD and TBS significantly decreased in the menopausal transition, suggesting that this period should be considered by clinicians as a key time during which to assess bone health and modifiable risk factors in WWH.

Frailty and post-operative delirium influence on functional status in patients with hip fracture: the GIOG 2.0 study.

BACKGROUND: This study analyzes the effect of frailty and Post-Operative Delirium (POD) on the functional status at hospital discharge and at 4-month follow-up in patients with hip fracture (HF). METHODS: Multicenter prospective observational study of older patients with HF admitted to 12 Italian Orthogeriatric centers (July 2019-August 2022). POD was assessed using the 4AT. A 26-item Frailty Index (FI) was created using data collected on admission. The outcome measures were Cumulated Ambulation Score (CAS) ≤ 2 at discharge and a telephone-administered CAS ≤ 2 after 4 months. Poisson regression models were used to assess the effect of frailty and POD on outcomes. RESULTS: 984 patients (median age 84 years, IQR = 79-89) were recruited: 480 (48.7%) were frail at admission, 311 (31.6%) developed POD, and 158 (15.6%) had both frailty and POD. In a robust Poisson regression, frailty alone (Relative Risk, RR = 1.56, 95% Confidence Intervals, CI 1.19-2.04, p = 0.001) and its combination with POD (RR = 2.57, 95% CI 2.02-3.26, p < 0.001) were associated with poor functional status at discharge. At 4-month follow-up, the combination of frailty with POD (RR 3.65, 95% CI 1.85-7.2, p < 0.001) increased the risk of poor outcome more than frailty alone (RR 2.38, 95% CI 1.21-4.66, p < 0.001). CONCLUSIONS: POD development exacerbates the negative effect that frailty exerts on functional outcomes in HF patients.

Efficacy of a multiple-component and multifactorial personalized fall prevention program in a mixed population of community-dwelling older adults with stroke, Parkinson's Disease, or frailty compared to usual care: The PRE.C.I.S.A. randomized controlled trial.

Background: Fall risk in the elderly is a major public health issue due to the injury-related consequences and the risk of associated long-term disability. However, delivering preventive interventions in usual clinical practice still represents a challenge. Aim: To evaluate the efficacy of a multiple-component combined with a multifactorial personalized intervention in reducing fall rates in a mixed population of community-dwelling elderly compared to usual care. Design: Randomized Controlled Trial (NCT03592420, clinicalTrials.gov). Setting: Outpatients in two Italian centers. Population: 403 community-dwelling elderly at moderate-to-high fall risk, including subjects with Parkinson's Disease and stroke. Methods: After the randomization, the described interventions were administered to the intervention group (n = 203). The control group (n = 200) received usual care and recommendations to minimize fall risk factors. In addition, each participant received a fall diary, followed by 12 monthly phone calls. The primary endpoint was the total number of falls in each group over 12 months, while the secondary endpoints were other fall-related indicators recorded at one year. In addition, participants' functioning was assessed at baseline (T1) and 3-month (T3). Results: 690 falls were reported at 12 months, 48.8% in the intervention and 51.2% in the control group, with 1.66 (± 3.5) and 1.77 (± 3.2) mean falls per subject, respectively. Subjects with ≥ 1 fall and ≥2 falls were, respectively, 236 (58.6%) and 148 (36.7%). No statistically significant differences were observed between groups regarding the number of falls, the falling probability, and the time to the first fall. According to the subgroup analysis, no significant differences were reported. However, a statistically significant difference was found for the Mini-BESTest (p = 0.004) and the Fullerton Advanced Balance Scale (p = 0.006) for the intervention group, with a small effect size (Cohen's d 0.26 and 0.32, respectively), at T1 and T3 evaluations. Conclusions: The intervention was ineffective in reducing the number of falls, the falling probability, and the time to the first fall at 12 months in a mixed population of community-dwelling elderly. A significant improvement for two balance indicators was recorded in the intervention group. Future studies are needed to explore different effects of the proposed interventions to reduce falls and consequences.

Combining L-Arginine with vitamin C improves long-COVID symptoms: The LINCOLN Survey.

INTRODUCTION: Recent evidence suggests that oxidative stress and endothelial dysfunction play critical roles in the pathophysiology of COVID-19 and Long-COVID. We hypothesized that a supplementation combining L-Arginine (to improve endothelial function) and Vitamin C (to reduce oxidation) could have favorable effects on Long-COVID symptoms. METHODS: We designed a survey (LINCOLN: L-Arginine and Vitamin C improves Long-COVID), assessing several symptoms that have been associated with Long-COVID to be administered nationwide to COVID-19 survivors; the survey also included effort perception, measured using the Borg scale. Patients receiving the survey were divided in two groups, with a 2:1 ratio: the first group included patients that received L-Arginine + Vitamin C, whereas the second group received a multivitamin combination (alternative treatment). RESULTS: 1390 patients successfully completed the survey. Following a 30-day treatment in both groups, the survey revealed that patients in the L-Arginine + Vitamin C treatment arm had significantly lower scores compared to patients who had received the multivitamin combination. There were no other significant differences between the two groups. When examining effort perception, we observed a significantly lower value (p < 0.0001) in patients receiving L-Arginine + Vitamin C compared to the alternative-treatment arm. CONCLUSIONS: Our survey indicates that the supplementation with L-Arginine + Vitamin C has beneficial effects in Long-COVID, in terms of attenuating its typical symptoms and improving effort perception.

Truly unexplained falls after evaluation for syncope: A new diagnostic entity with severe prognosis.

OBJECTIVE: To compare one-year mortality risk associated with syncope and unexplained fall in older adults with dementia. METHODS: 522 patients (aged >65 years) with dementia and history of transient loss of consciousness and/or unexplained falls were evaluated. The diagnosis of syncope was based on European Society of Cardiology guidelines. A "Syncopal Fall" was defined in patients with an initial clinical presentation of unexplained fall, but a final diagnosis of syncope after complete assessment. A "Truly Unexplained Fall" was defined in patients with an initial clinical presentation of unexplained fall, in whom a diagnosis of syncope had been excluded after the diagnostic work-up. One-year follow-up was assessed by phone interview. RESULTS: Follow-up data were available for 501 participants (mean age 83 ± 6 years, 65% female). After a mean follow-up of 324 ± 93 days, death from any cause was reported in 188 participants (24%). Advanced age, male sex, cognitive and functional impairment were associated with a higher mortality rate. Patients with "Truly Unexplained Falls" had a higher mortality risk compared with syncope and "Syncopal Fall". A diagnosis of "Truly Unexplained Falls" remained an independent predictor of one-year all-cause mortality in multivariate model. CONCLUSIONS: We propose the novel diagnostic category of "Truly Unexplained Fall", resulting from the application of syncope guidelines to subjects with unexplained falls. This condition in older adults with dementia is a predictor of one-year all-cause mortality. For this new high risk profile, we advice a comprehensive geriatric assessment focused on risk factors for fall, aimed at a possible improvement of prognosis.

Use of Lipid-Lowering Drugs and Associated Outcomes According to Health State Profiles in Hospitalized Older Patients.

OBJECTIVE: To assess how lipid-lowering drugs (LLDs) are administered in the hospitalized patients aged 65 and older and their association with clinical outcomes according to their health-related profiles. DESIGN: This is a retrospective study based on data from REPOSI (REgistro POliterapie SIMI - Italian Society of Internal Medicine) register, an Italian network of internal medicine hospital wards. SETTING AND PARTICIPANTS: A total of 4642 patients with a mean age of 79 years enrolled between 2010 and 2018. METHODS: Socio-demographic characteristics, functional abilities, cognitive skills, laboratory parameters and comorbidities were used to investigate the health state profiles by using multiple correspondence analysis and clustering. Logistic regression was used to assess whether LLD prescription was associated with patients' health state profiles and with short-term mortality. RESULTS: Four clusters of patients were identified according to their health state: two of them (Cluster III and IV) were the epitome of frailty conditions with poor short-term outcomes, whereas the others included healthier patients. The average prevalence of LLD use was 27.6%. The lowest prevalence was found among the healthier patients in Cluster I and among the oldest frail patients with severe functional and cognitive impairment in Cluster IV. The highest prevalence was among multimorbid patients in Cluster III (OR=4.50, 95% CI=3.76-5.38) characterized by a high cardiovascular risk. Being prescribed with LLDs was associated with a lower 3-month mortality, even after adjusting for cluster assignment (OR=0.59; 95% CI = 0.44-0.80). CONCLUSION: The prevalence of LLD prescription was low and in overall agreement with guideline recommendations and with respect to patients' health state profiles.

Prevalence and management of delirium in community dwelling older people with dementia referred to a memory clinic.

OBJECTIVE: Our aim was to measure the prevalence of delirium, its clinical features, and outcomes in older patients referred to a memory clinic. METHODS: A retrospective cohort study of 109 older outpatients with delirium referred to a memory clinic with a home care service. Delirium was diagnosed using the confusion assessment method and dementia with the DSM-5 criteria. We collected information on cognitive and functional status, mortality, institutionalization, and hospitalization during 6 months following the delirium episode. RESULTS: Delirium prevalence was 3.6%, mostly of hyperactive type. Delirium worsened functional (ADL 2.95 ± 1.95 vs. 2.16 ± 1.84) and cognitive (MMSE 13.88 ± 8.96 vs.11.0 ± 9.49) status after 6 months compared to the baseline. The mortality rate was 29.4%, and 28.3% were admitted to a long-term facility after the episode of delirium. Of these patients, more than half were hospitalized during the follow-up. Of the 109 patients with delirium, 85 were managed at home and 24 were hospitalized. Patients who were hospitalized had more severe behavioral symptoms during the delirium episode. There was no difference in mortality and institutionalization according to the home or hospital management. CONCLUSIONS: This retrospective cohort study adds novel information to the existing literature of an understudied setting and population. The study supports the need to further investigate the feasibility and efficacy of the hospital at home models for the prevention and management of delirium in a high-risk population.

Cognitive impairment in patients with atrial fibrillation: Implications for outcome in a cohort study.

BACKGROUND: The impact of cognitive status on outcomes of patients with atrial fibrillation (AF) is not well defined. AIMS: To assess the prevalence of cognitive impairment in AF patients and evaluate its association with: i) all-cause mortality; ii) a composite endpoint of death, stroke/systemic embolism, hemorrhages, acute coronary syndrome, pulmonary embolism, new/worsening heart failure. METHODS: In a cohort study, cognitive status was assessed at baseline by the Mini Mental State examination adjusted for age and education (aMMSE). aMMSE <24 was considered indicative of cognitive impairment. RESULTS: The cohort included 437 patients (61.3% male, mean age 73.4 ± 11.7 years). Sixty-three patients (14.4%) had cognitive impairment at baseline aMMSE. Permanent AF (odds ratio [OR] 1.750; 95%CI 1.012-3.025; p = .045), haemoglobin levels (OR 0.827; 95%CI 0.707-0.967; p = .017) and previous treatment with antiplatelet drugs only, without oral anticoagulation, (OR 4.352; 95%CI 1.583-11.963; p = .004) were independently associated with cognitive impairment at baseline. After a median follow-up of 887 days (interquartile range 731-958) 30 patients died (7.1%), and 97 (22.9%) reached the composite endpoint. After adjustment for Elixhauser Comorbidy Measure, aMMSE <24 was significantly associated with all-cause mortality (hazard ratio [HR] 2.473, 95%CI 1.062-5.756, p = .036) and with the composite endpoint (HR 1.852, 95%CI 1.106-3.102, p = .019). CONCLUSIONS: In patients with AF, cognitive impairment (aMMSE <24) is associated with worse outcomes, and the association of adverse outcomes with previous treatment with antiplatelet drugs only, without oral anticoagulation, highlights the potential role of appropriate antithrombotic treatment for improving patient prognosis.

Atrial Fibrillation in Older Patients with Syncope and Dementia: Insights from the Syncope and Dementia Registry.

OBJECTIVES: To evaluate the clinical characteristics and the long-term outcome of atrial fibrillation (AF) patients with dementia and history of syncope or falls. DESIGN: Observational: analysis of a prospective registry. SETTING AND PARTICIPANTS: Between 2012 and 2016, the Syncope and Dementia Registry enrolled patients in 12 geriatric departments. Follow-up evaluation was at 12 months. MEASURES: Clinical, functional, and cognitive assessment. RESULTS: Of the 522 patients (women, 62.1%; Mini-Mental State Examination 17 ± 6), 26.4% have or presented an AF history. Patients with AF were older (85 ± 6 vs 83 ± 6 years, P = .012), with higher heart rate (78 ± 17 vs. 73 ± 14 bpm, P < .001), prescribed drugs (6.9 ± 2.9 vs 5.9 ± 2.7, P < .001), and an increased number (3.9 ± 2.0 vs 3.0 ± 1.8, P < .001) and severity of comorbidities. Oral anticoagulant therapy was underprescribed (39.9%). Cardiac syncope was more frequently diagnosed (18.8 vs 4.9%, P < .001). At multivariate analysis, AF patients were characterized by advanced age, a higher severity of comorbidities, a greater number of prescribed drugs, an increased heart rate, and a more frequent presence of cardiac symptoms. One-year mortality differed little between patients with and without AF (27.7 vs 22.1%, P = .229). In the arrhythmia group, multivariate predictors of prognosis were disability (number of lost BADLs; P = .020) and a higher heart rate (P = .006). CONCLUSIONS AND IMPLICATIONS: AF and postural stability-related issues often co-exist in persons with dementia. This complex of conditions is associated with an intricate clinical picture, underprescription of oral anticoagulants, and high long-term mortality. Future studies are needed to evaluate the effects of therapy optimization in this population.

Three-year National report from the Gruppo Italiano di Ortogeriatria (GIOG) in the management of hip-fractured patients.

BACKGROUND: Hip fractures (HF) are a major issue worldwide. We aimed at evaluating the practices in delivering care to patients with HF among several Italian Orthogeriatric centers. METHODS: The study took place from February 2016 to July 2018. Seven performance indicators (pre-surgical cognitive assessment, surgery performed ≤ 48 h from fracture, removal of urinary catheter/absence of delirium/start of physiotherapy on the first post-operative day, prescription of bone protection at discharge, and discharge toward rehabilitation) were collected. RESULTS: The 14 participating hospitals totally recruited 3.017 patients. Patients were old (median age 86 years; Inter Quartile Range [IQR] 80-90), mostly females (77%). Nearly 55% of them were already impaired in mobility and about 10% were nursing home residents. Median time-to-surgery was 41 h (IQR 23-62). Models of care greatly varied among centers, only 49.3% of patients being co-managed by geriatricians and orthopedics. There was high variability across centers in four indicators ("pre-surgical cognitive assessment", "bone protection prescription", "use of urinary catheter" and "start of physiotherapy"), moderate in two indicators ("surgery performed ≤ 48 h from fracture" and "discharge toward rehabilitation" and low in one ("absence of delirium on day following surgery"). Comparison with international studies suggests very different ways of providing care to HF Italian patients. CONCLUSIONS: The study results suggest high inter-center variability in the key-performance indicators, and different approaches in providing care to our HF patients in comparison to other countries. A National debate on the topic is required in Italy to harmonize practices of orthogeriatric care.

Compression of frailty in adults living with HIV.

BACKGROUND: Contemporary HIV care may reduce frailty in older adults living with HIV (OALWH). Objective of the study was to estimate prevalence of frailty at the age of 50 and 75 years, and build a model to quantify the burden of frailty in the year 2030. METHODS: This study included OALWH attending Modena HIV Metabolic Clinic between 2009 and 2015. Patients are referred from more than 120 HIV clinics well distributed across Italy, therefore being country representative. Our model forecasts the new entries on yearly basis up to 2030. Changes in frailty over a one-year period using a 37-variable frailty index (FI) and death rates were modelled using a validated mathematical algorithm with parameters adjusted to best represent the changes observed at the clinic. In this study, we assessed the number of frailest individuals (defined with a FI > 0.4) at the age of 50 and at the age 75 by calendar year. RESULTS: In the period 2015-2030 we model that frailest OALWH at age 50 will decrease from 26 to 7%, and at the age of 75 years will increase from 43 to 52%. This implies a shift of the frailty prevalence at an older age. CONCLUSION: We have presented projections of how the burden of frailty in older adults, living with HIV will change. We project fewer people aged 50+ with severe frailty, most of whom will be older than now. These results suggest a compression of age-related frailty.

Management of high cholesterol levels in older people.

The management of hypercholesterolemia in older adults still represents a challenge in clinical medicine. The pathophysiological alterations of cholesterol metabolism associated with aging are still incompletely understood, even if epidemiological evidence suggests that serum cholesterol levels increase with ongoing age, possibly with a plateau after the age of 80 years. Age is also one of the main determinants of cardiovascular disease, according to all cardiovascular risk estimate tools. Cholesterol-lowering treatment, therefore, would be expected to bring significant protection, even in these patients. Unfortunately, direct experimental evidence is extremely limited, particularly in the very old age strata of the population; a clinical benefit still seems to be present, but the risk for drug-related adverse events is clearly higher. At any rate, at the present time, definite guidelines for the correct management of hypercholesterolemia in older patients are not available. Therefore, the decision whether or not a pharmacological treatment should be set up, and the choice of the drug, need to be tailored to the individual patient, and requires accurate clinical judgment. The specific aspects of frailty and disability, along with the actual age of the patients, have to be considered together, with a comprehensive assessment approach. The present review summarizes the evidence regarding the modifications of cholesterol metabolism in older patients, the impact of lipid-lowering drugs on cardiovascular outcomes and focuses on the considerations that can help to define the most appropriate treatment strategy, in view of the individual functional profile. Geriatr Gerontol Int 2019; 19: 375-383.

Prevalence, predictors and clinical implications of prolonged corrected QT in elderly patients with dementia and suspected syncope.

BACKGROUND: Long QT and use of QT-prolonging drugs are common among older patients receiving polytherapies, but real-world evidence on their impact in clinical practice is controversial. We investigated prevalence, variables associated and clinical implications of prolonged corrected QT (QTc) among patients from the Syncope and Dementia study. METHODS: Observational, prospective, multicenter study. Patients≥65 years with dementia and fall suspected for syncope in the previous three months were enrolled. Several clinical variables and the complete list of medications were recorded for each patient. A 12­lead ECG was obtained and corrected QT was calculated by the Bazett's formula. One-year followup for death and recurrent syncope was performed. RESULTS: Prolonged QTc was observed in 25% of the 432 enrolled patients (mean age 83.3), and was significantly associated with male gender (OR 2.09; 95% CI 1.34-3.26) and diuretics use (OR 1.85; 95% CI 1.18-2.90). At one-year 23.3% of patients died and 30.4% reported at least one recurrent event. Variables associated with one-year mortality were: age, male gender, atrial fibrillation (AF), use of calcium channel blockers and prolonged QTc (OR 1.80; 95% CI 1.01-3.20). Among patients with prolonged QTc a significant interaction for mortality was found with AF. Recurrent events were associated with the use of antiplatelets, cholinesterase. inhibitors and antipsychotics, but not with prolonged QTc. CONCLUSIONS: We documented a high prevalence of prolonged QTc, that was associated with male gender and diuretics but not with psychoactive medications. Patients with prolonged QTc had higher one-year mortality, that was four-fold increased in those with concomitant AF.

Hypotensive Drugs and Syncope Due to Orthostatic Hypotension in Older Adults with Dementia (Syncope and Dementia Study).

OBJECTIVES: To determine whether hypotensive drugs may play a pivotal role in inducing orthostatic hypotension (OH)-related syncope. DESIGN: Prospective, observational, multicenter study. SETTING: Acute care wards, syncope units, and centers for the diagnosis of dementia. PARTICIPANTS: Individuals aged 65 and older with a diagnosis of dementia and 1 or more episodes of transient loss of consciousness of a suspected syncopal nature or unexplained falls during the previous 3 months MEASUREMENTS: Blood pressure was measured in the supine position and in the orthostatic position after 1 and 3 minutes. OH was defined as a decrease in systolic blood pressure of 20 mmHg or more and in diastolic blood pressure of 10 mmHg or more within 3 minutes of standing. Univariate and multivariate analyses were used to evaluate associations between hypotensive drugs and their combinations with OH-related syncope. RESULTS: The mean age of the study population (n=522; women, n=324) was 83.5±6.1, and the most frequent comorbidity was arterial hypertension (74.5%); 324 (67.8%) participants had had a syncopal fall and 168 (32.2%) a nonsyncopal fall. The mean number of hypotensive drugs administered (2.9±3.1) did not differ between the two groups. Syncopal falls was OH-related in 170 participants (48.0%). OH-related syncopal falls were more frequent in participants receiving nitrates (15.3% vs 9.8%, p=.06), alpha-blockers (16.5% vs 9.8%, p=.04), or combinations of angiotensin-converting enzyme inhibitors (ACE-Is) and diuretics (20.6% vs 13.0%, p=.04), alpha-blockers and diuretics (8.2% vs 3.3%, p=0.036), and ACE-Is and nitrates (8.2% vs 3.3%, p=.10). Multivariate analysis confirmed a greater risk of OH-related syncopal fall for nitrates (relative risk (RR)=1.77), combinations of ACE-Is and diuretics (RR=1.66), and combinations of ACE-Is and nitrates (RR=2.32). CONCLUSION: In older adults with dementia, OH-related syncopal falls are significantly related to treatment with nitrates, combinations of ACE-Is and diuretics, and combinations of ACE-Is and nitrates.