Misdiagnosis and Mistreatment of a Rare Case of Intracranial Oncogenic Osteomalacia with an Altered Amino Acid Profile.

Background. Oncogenic osteomalacia (OO), also known as tumor-induced osteomalacia (TIO), is a rare paraneoplastic syndrome caused by mesechymal tumors secreting fibroblast growth factor 23 (FGF23). Common in middle age, these tumors are often disclosed by progressive generalized bone pain and muscle weakness, along with an altered biochemical profile. Despite its characteristic presentation, the disease is often underrecognized with delayed onset of surgical or pharmacological intervention that can have serious repercussions on the patients' health and quality of life. Case presentation. We describe the case of a 65-year-old Caucasian man presenting TIO with intracranial and spinal localizations and Fanconi-like aminoaciduria. The condition was misdiagnosed and mistreated for three years, leading to loss of self-sufficiency and depression. Following proper identification, the spinal mass was excised with complete remission of the functional symptoms. As it was not possible to remove the intracranial lesion, the patient was treated conservatively with calcitriol and phosphorous supplements that granted good metabolic control up to the time of a recent follow-up visit (at 5 years). Conclusions. The finding of an altered amino acid profile, not usually reported in these cases, should prompt clinicians to a wider usage of these molecules as suitable candidates for metabolic diseases. In addition to providing central information, they are easy to obtain and inexpensive to analyze. Such determination could help to speed up the diagnostic process, as a long-lasting history of misdiagnosis and mistreatments can lead primarily to clinical worsening, but also to the use of expensive, useless medications with side effects that contribute to poor patient health.

Bone-related polymorphisms and dental status in older men and women. Results of the longitudinal Pro.V.A. study.

BACKGROUND/PURPOSE: Genetics plays a role in the susceptibility to periodontitis and tooth loss. Several studies examined the involvement of polymorphisms in candidate genes. We hypothesize that bone metabolism-related polymorphisms could be associated with the number of remaining teeth. MATERIALS AND METHODS: Participants in the Pro.V.A. longitudinal Study: 3099 Italians (aged 65+ at baseline), 2196 at follow-up 1 (5yrs), 1641 at follow-up 2 (7yrs) underwent detailed interview and clinical-instrumental examination. Subjects, grouped by remaining teeth number (0, 1-7, 8-19, 20+), were genotyped for six different bone-related polymorphisms: collagen type Iα1 (COL1A1, Sp1, Ss alleles, n = 1068), vitamin D receptor (VDR, Fok I, Ff alleles, n = 300), calcitonin receptor (CALCR, Alu I, CT alleles, n = 1430), estrogen receptor alpha (ESR1, Pvu II and Xba I, Pp and Xx alleles, n = 1335 and n = 1324). RESULTS: COL1A1 associated with dental status: ss carriers had reduced incident tooth loss (p < 0.05). The low frequency of this genotype, 3.6% in the whole population, didn't grant sufficient statistical power to other findings, such as the lower prevalence of edentulism, consistent throughout the study. In men, CC genotype of CALCR was associated with higher tooth loss between follow ups (p < 0.05). Biochemical markers of inflammation didn't differ by genotype. Confounders such as diabetes, neoplasms, and smoking hampered the detrimental effect of S allele in the logistic regression analysis (OR = 0.67, 95% CI 0.4-1.0, p = 0.06). CONCLUSION: The present study, demonstrating an association between tooth loss and COL1A1 and -in men- CALCR, contributes to the identification of genes involved in tooth loss and, possibly, susceptibility to periodontitis.

Tooth retention predicts good physical performance in older adults.

BACKGROUND: Oral health is closely related to both physical and psychological well-being, as it enables individuals to eat, speak, and socialize. The number of teeth is the most used indicator of oral health. Several reports document a relationship of dental status with a variety of indicators of general health but longitudinal studies employing standardized physical performance tests are infrequent in the scientific literature. SUBJECTS AND METHODS: The Italian elderly participating in the Pro.V.A. longitudinal Study (3099 subjects aged 65+ at baseline, 2196 at the 5-year follow-up 1 and 1641 at the 7-year follow- up 2) underwent detailed interview and extensive clinical and instrumental examination that included validated physical performance measures. Participants were classified into 4 groups according to the number of remaining teeth: 0, 1-7, 8-19, and 20+. To explore the association of the number of remaining teeth with physical function and disability, we performed logistic regression analyses with models progressively adjusted for a wide number of covariates, namely anthropometric (gender, age, BMI), comorbidity (cardio-vascular, osteoarticular, and neurological diseases including depression), muscle strength (assessed for upper and lower limbs), lifestyle (smoking status, alcohol use, leisure time activities) and socioeconomical status (education, income, marital status, loneliness). RESULTS: Dental status correlated with most comorbidities, lifestyle, and socio-economic variables at the univariate analysis at baseline and at follow-ups. A good dental status was significantly associated with better physical functioning and lower disability. The presence of 20+ teeth resulted significantly protective (reference group: 0 teeth) versus mobility-related disability (OR = 0.67), disability (OR = 0.54) and inability to perform heavy duties (OR = 0.62), at follow up 1 and low physical performance score (OR = 0.59) at follow up 2. Conversely, the detrimental effect of edentulism, explored in subjects with or without dentures, was present but not as straightforward. Conclusion. The assessment of a geriatric patient should include an oral evaluation as a good dental status is a crucial component of successful aging.

Parathyroidectomy Resolves Tooth Discoloration: A New Presenting Sign of Hyperparathyroidism?

INTRODUCTION: We report the resolution of tooth discoloration following parathyroidectomy in an otherwise asymptomatic woman with primary hyperparathyroidism-associated hypercalcemia. Case Report. A 59-year-old Caucasian woman, diagnosed with primary hyperparathyroidism in 2011, nonsmoker with excellent overall oral health. She complained of tooth discoloration starting in 2013. Pigmentation was particularly evident in the necks of the lower central and lateral incisors (Vita Classical score C2). No bleaching was undertaken. Parathyroidectomy was performed five years after primary hyperparathyroidism diagnosis. Six months later, a reduction in pigmentation was strikingly evident, with incisors scoring A1 and A2. The improvement persisted over time. Tooth value also increased compared to baseline. CONCLUSIONS: This is, to our knowledge, the first report that parathyroidectomy might resolve dental discoloration. This outcome deserves investigation in a meaningful sample size and may eventually prompt the inclusion of dental issues among the consequences of primary hyperparathyroidism.

Zoledronic acid for the treatment of pregnancy-associated femoral head necrosis: A case report.

INTRODUCTION: The management of pregnancy-associated femoral necrosis is controversial. Conservative management may eventually lead to hip replacement. CASE: A 40-year-old woman developed necrosis of the left hip during her first pregnancy. Treatment with zoledronic acid three months after delivery resulted in rapid reduction of the necrotic area. The patient's second pregnancy shortly afterwards had no complications. A magnetic resonance scan three years later documented complete resolution. CONCLUSION: Femoral head necrosis should be suspected in the differential diagnosis of pain in pregnancy. Zoledronic acid given in the early stages prevented progression to hip arthritis in this case.

Bone regeneration in the stem cell era: safe play for the patient?

The past decade has seen outstanding scientific progress in the field of stem cell (SC) research and clinical application. SCs are convenient both technically and biologically: they are easy to find and to culture and they can differentiate in virtually all tissues and even in whole organs. Induced pluripotent stem cells (iPSs) are a type of pluripotent SC generated in vitro directly from mature cells through the introduction of key transcription factors. The use of iPSs, however tantalizing, poses serious safety concerns because of their genomic instability. Recently, it has been suggested that the main mechanism of SC action relies on paracrine signals. Therefore, the secretome would be primarily responsible for SC effects. The therapeutical use of secretome is safer and more reliable and offers manufacturing, handling and transportation advantages. The authors discuss current applications of SCs with particular respect to bone regeneration stressing the possible risks that may arise from incautious employments of SCs-particularly when associated with stimulating factors. Safety issues hamper the advancement of SC-based innovative therapies and raise the need for novel standards to adequately address and rule out inconsistency and other concerns, considering the permanent nature of SC treatments. Many biological aspects concerning dose, time and site of administration are still to be elucidated. Solid clinical data and trials with long-term follow-ups are highly recommended as a means to evaluate the risk/benefit ratio of each potential intervention and to provide patients with clear and accurate information.

Poor Physical Performance Predicts Future Onset of Depression in Elderly People: Progetto Veneto Anziani Longitudinal Study.

BACKGROUND: Reduced physical performance is predictive of deleterious outcomes in older adults. Data considering objective physical performance and incident depression are sparse. OBJECTIVE: The objective of this study was to investigate during a 4-year study whether objective physical performance can predict incident depression among older adults who do not have depression at the baseline. DESIGN: This was a longitudinal study. METHODS: From 3,099 older people initially enrolled in the Progetto Veneto Anziani study, 970 participants without depression at the baseline were included (mean age = 72.5 years; 54.6% women). Physical performance measures included the Short Physical Performance Battery, 4-m gait speed, Five-Times Sit-to-Stand test, leg extension and flexion, handgrip strength, and 6-minute walk test, categorized in sex-specific tertiles. Depression was classified on the basis of the Geriatric Depression Scale and a diagnosis from a geriatric psychiatrist. Area under the curve and logistic regression analyses were conducted. RESULTS: At the baseline, participants developing depression during the follow-up (n = 207) scored significantly worse across all physical performance measures than those who did not develop depression. The area under the curve and predictive power were similar for all of the physical performance tests assessed. In the logistic regression analysis, after adjustment for 14 potential confounders, worse physical performance across all tests increased the risk of depression. Participants in the lowest tertile of the Short Physical Performance Battery were at notable odds of developing depression (odds ratio = 1.79; 95% CI = 1.18-2.71). The association between poor physical performance and depression was typically stronger in women than in men, except for 4-m gait speed. LIMITATIONS: No gold standard was used for a depression diagnosis; oxidative stress and inflammatory markers were not included; and there was a high rate of missing data at the follow-up. CONCLUSIONS: Low physical performance appeared to be an independent predictor of depression over a 4-year follow-up in a sample of elderly people.

Results of an Observational Cohort Study of Hyperuricemia as a Predictor of Poor Physical Performance in the Elderly.

OBJECTIVE: Hyperuricemia is frequent in older people and associated with several medical conditions. The relationship between hyperuricemia and physical performance is limited. We aimed to investigate the association between hyperuricemia and physical performance over a 4.4-year followup in the elderly. METHODS: A total of 1,904 community-dwelling older participants were followed for a mean of 4.4 years. Hyperuricemia at baseline was defined using serum uric acid concentrations ≥6 and ≥7 mg/dl for women and men, respectively. Objective physical performance tests measured included the Short Physical Performance Battery (SPPB), 4-meter gait speed, chair-stands time, leg extension and flexion, handgrip strength, and the 6-minute walking test. RESULTS: At baseline, participants with hyperuricemia (n = 98 men, 232 women) scored significantly worse in all the tests investigated. After adjusting for 19 covariates, men with hyperuricemia at baseline had an increased risk of having poor SPPB scores at followup (odds ratio [OR] 1.44 [95% confidence interval (95% CI) 1.21-1.72]; P < 0.0001), poor chair-stands time (OR 1.40 [95% CI 1.18-1.6]; P < 0.0001), poor leg extension (OR 1.47 [95% CI 1.21-1.7]; P < 0.0001), and poor handgrip strength (OR 1.54 [95% CI 1.24-1.90]; P < 0.0001). Among women, hyperuricemia was associated with an increased risk of having poor scores in all the SPPB items and in leg flexion (OR 1.26 [95% CI 1.08-1.49]; P = 0.03). CONCLUSION: Hyperuricemia seems to be significantly associated with poor physical performance in older people, over a followup of 4.4 years. The relationship appears to be more consistent in men than in women. Further longitudinal research is required to better understand the relationships and potential biologic pathways.

Factors Influencing Transitions Between Frailty States in Elderly Adults: The Progetto Veneto Anziani Longitudinal Study.

OBJECTIVES: To investigate frailty state transitions in a cohort of older Italian adults to identify factors exacerbating or improving frailty conditions. DESIGN: Population-based longitudinal study with mean follow-up of 4.4 years. SETTING: Community. PARTICIPANTS: Individuals enrolled in the Progetto Veneto Anziani (Pro.V.A.) (N = 2,925; n = 1,179 male, n = 1,746 female; mean age 74.4 ± 7.3). MEASUREMENTS: Frailty was identified at baseline and follow-up based on the presence of at least three Fried criteria; prefrailty was defined as the presence of one or two Fried criteria. Anthropometric, socioeconomic, and clinical characteristics were assessed at baseline in a personal interview and clinical examination using validated scales and medical history. RESULTS: During the study period, 1,114 (38.1%) subjects retained their baseline frailty status, 1,066 (36.4%) had a transition in frailty status, and the remainder of the sample died. Older age, female sex, obesity, cardiovascular disease, osteoarthritis, smoking, loss of vision, low levels of self-sufficiency and physical performance, cognitive impairment, hypovitaminosis D, hyperuricemia, and polypharmacy were associated with increasing frailty and greater mortality. Conversely, overweight, low to moderate drinking, high educational level, and living alone were associated with decreasing frailty. CONCLUSIONS: Frailty was confirmed as a dynamic syndrome, with socioeconomic and clinical factors that could be targets of preventive actions influencing transitions to better or worse frailty status.

Hyperuricemia, Cardiovascular Profile, and Comorbidity in Older Men and Women: The Pro.V.A. Study.

Hyperuricemia (HU) is growing worldwide and associates with several medical conditions in the elderly. However, data about older people and possible gender differences are sparse. The aim of this study was to compare HU prevalence rates and association with relevant medical disorders in elderly subjects of both sexes. Pro.V.A. is a survey of 3099 individuals aged 65+, focusing on chronic diseases and disability. Uric acid (UA) levels were dichotomized using 6.0 mg/dL (females) and 7.0 mg/dL (males), and multivariate logistic regression models were used to estimate odds ratios (ORs) between HU and single comorbidity. HU prevalence was 21.5% in females and 15.8% in males. HU was associated with most anthropometric and laboratory variables in women, but not in men. After adjustment for age, body mass index, and renal function, HU was independently associated with the presence of cardiovascular diseases in both sexes. In women, HU was associated with hand osteoarthritis (OR = 1.52; 95%CI: 1.12-2.08) and edentulism (OR = 1.31; 95%CI: 1.01-1.71), while resulted protective for osteoporosis (OR = 0.69; 95%CI: 0.53-0.91). In men, HU was significantly related with knee osteoarthritis (OR = 1.72; 95%CI: 1.06-2.79) and chronic obstructive pulmonary disease (OR = 1.60; 95%CI: 1.04-2.45). The presence of ≥4 comorbidities was a stronger determinant of HU in men (OR = 2.54; 95%CI: 1.21-5.37) than in women (ns). Patterns of age-dependent UA increase are markedly different in men and women. HU prevalence is substantial and its association with other diseases is gender specific, connoting a peculiar clinical profile.

A Comparison of Objective Physical Performance Tests and Future Mortality in the Elderly People.

Background: Physical performance is an important predictor of mortality, but little is known on the comparative prognostic utility of different objective physical performance tests in community-dwelling older adults. We compared the prognostic usefulness of several objective physical performance tests on mortality, adjusting our analyses for potential confounders. Methods: Among 3,099 older community-dwelling participants included in the Progetto Veneto Anziani study, 2,096 were followed for a mean of 4.4 years. Physical performance tests measured were Short Physical Performance Battery (SPPB), 4-meter gait speed, chair stands time, leg extension and flexion, handgrip strength, and 6-Minute Walking Test (6MWT), treated as continuous variables and categorized in gender-specific quartiles. The main outcome was mortality assessed with death certificates. Results: Participants who died during the follow-up (n = 327) scored significantly worse in all physical performance tests measured at baseline than those who survived (n = 1,769). Using a Harrell's C-index, the highest C-index was observed for 6MWT in men (C-index = 0.735; 95% confidence interval [CI]: 0.701-0.770, p < .0001) and SPPB in women (C-index = 0.781; 95% CI: 0.740-0.822, p = .0009). However, in both genders, only SPPB, 4-meter walking speed, and 6MWT are significant predictors of mortality. Analyses using sex-specific quartiles substantially confirmed these findings. Conclusions: Slow gait speed, 6MWT, and SPPB are significant predictors for mortality in community-dwelling older men and women. Physicians should consider using these tests to identify elderly individuals who are at higher risk of death to improve clinical decision making.

Pain Increases the Risk of Developing Frailty in Older Adults with Osteoarthritis.

Objective: While osteoarthritis (OA)-related pain increases the risk of physical inactivity, disability, and falls, less is known about whether pain increases the risk of frailty. We investigated if people with OA reporting pain are more likely to develop frailty than people with OA without pain. Design: Population-based prospective cohort study with a follow-up of 4.4 years. Setting: Community. Subjects: The subjects were 1,775 older men and women with osteoarthritis, enrolled in the Progetto Veneto Anziani. Methods: Pain was ascertained according to medical records, symptoms/signs, and use of analgesics. Participants were considered frail if they met three out of five criteria of Fried's Index. Results: Cross-sectional analysis at baseline demonstrated that after adjusting for potential confounders (age, gender, anthropometric and demographic data, comorbidities), people with OA and pain (n = 568) were significantly more likely to have frailty compared with those with OA without pain (n = 1,207; hand OA, OR = 1.86, 95% CI = 1.65-2.09; hip OA, OR = 1.62, 95% CI = 1.44-1.83; knee OA, OR = 1.42, 95% CI = 1.26-1.60; all p < 0.0001). Prospective analysis of 1,152 nonfrail subjects at baseline demonstrated that 19.9% developed incident frailty. A fully-adjusted logistic regression analysis demonstrated that lower limb OA-related pain was associated with an increased risk of developing frailty compared with people with OA and no pain. Conclusions: Pain related to OA might be an important factor influencing the relationship between OA and the development of frailty.

Low Hemoglobin Levels and Risk of Developing Depression in the Elderly: Results From the Prospective PRO.V.A. Study.

OBJECTIVE: Low hemoglobin negatively affects health in the elderly, but research about the association with risk for depression is limited. We investigated the association between baseline hemoglobin concentrations and incident depression in a cohort of nondepressed elderly individuals. METHODS: As part of the Northern Italian Progetto Veneto Anziani (PRO.V.A.) study, randomly drawn, community-dwelling subjects aged ≥ 65 years underwent prospective clinical and laboratory assessments between October 1995 and December 2002. The association between baseline hemoglobin and depression was assessed with adjusted Cox regression analyses. Baseline serum hemoglobin concentrations were further categorized in gender-specific tertiles; anemia was defined as serum hemoglobin < 13 g/dL for men and < 12 g/dL for women. Moreover, hemoglobin concentration was measured at follow-up, and changes in concentration from baseline to follow-up were investigated. Depression was defined by a score of ≥ 11/30 on the validated Geriatric Depression Scale and confirmed by psychogeriatric specialists. RESULTS: Among 1,303 elderly individuals (566 men, 737 women) without depression at baseline, 294 subjects (177 women, 117 men; global incidence rate = 50 [95% confidence interval (CI), 0-170] per 1,000 patient years) developed depression during 4.4 years of follow-up. Low baseline serum hemoglobin concentration was most strongly associated with incident depression at follow-up in men (hazard ratio [HR] = 1.39; 95% CI, 1.12-1.69; P = .002), but not in women (P = .50). Men with the lowest baseline tertile hemoglobin concentration (HR = 1.68; 95% CI, = 1.02-3.08; P = .04) or with anemia (HR = 2.02; 95% CI, = 1.13-3.64; P = .02) had greater risk of depression, whereas findings were nonsignificant for women. Low follow-up hemoglobin concentration in men was less strongly associated with incident depression (HR = 1.15; 95% CI, 1.01-1.33; P = .05), as were the lowest endpoint tertile hemoglobin concentration (P = .03) and presence of anemia (P = .05). CONCLUSIONS: Low baseline hemoglobin strongly predicted incident depression in older men, but not in women.​.

Hypovitaminosis D predicts the onset of orthostatic hypotension in older adults.

A number of small cross sectional studies have demonstrated that hypovitaminosis D (represented by low 25 hydroxyvitamin D (25OHD) levels) is associated with orthostatic hypotension (OH). We investigated if hypovitaminosis D is associated with the onset of OH in older adults over a follow-up of 4.4 years. 25OHD was categorized using sex-specific quartiles; OH was defined as a drop of ≤20 mm Hg in systolic or ≤10 mm Hg in diastolic blood pressure <3 minutes of standing. Among 1308 elderly without OH at baseline, using an adjusted logistic regression analysis and taking those with higher baseline serum 25OHD as reference, there was a significant increase in the onset of OH in those with lower serum 25OHD levels. The association was significant only in women when we stratified by sex. In conclusion, hypovitaminosis D predicts the onset of OH in older adults, particularly in women.

Orthostatic Changes in Blood Pressure and Cognitive Status in the Elderly: The Progetto Veneto Anziani Study.

We studied a cohort of 1408 older subjects to explore whether postural changes in blood pressure (BP; defined as orthostatic hypo- or hypertension) can predict the onset of cognitive deterioration. Orthostatic hypotension was defined as a drop of 20 mm Hg in systolic or 10 mm Hg in diastolic BP and orthostatic hypertension as a rise of 20 mm Hg in systolic BP. Orthostatic BP values were grouped into quintiles for secondary analyses. Two cognitive assessments were considered: (1) cognitive impairment, that is, Mini-Mental State Examination scores ≤24/30, and (2) cognitive decline (CD), that is, a 3-point decrease in Mini-Mental State Examination score from the baseline to the follow-up. At the baseline, the prevalence of orthostatic hypotension and hypertension was 18.3% and 10.9%, respectively. At the follow-up (4.4±1.2 years), 286 participants were found cognitively impaired and 138 had a CD. Using logistic regression analysis adjusted for potential baseline confounders, participants with orthostatic hypertension were at significantly higher risk of CD (odds ratio =1.50; 95% confidence intervals =1.26-1.78). Neither orthostatic hypotension nor orthostatic hypertension raised the risk of developing a cognitive impairment. Using quintiles of orthostatic BP values, we found that both decreases and increases in systolic and diastolic BP raised the risk of CD, but not of cognitive impairment. In conclusion, we found that orthostatic hypertension predicts the onset of CD, but not of cognitive impairment in the elderly, whereas orthostatic hypotension predicts neither of these conditions. Further studies are needed to confirm our findings.

Frailty Is Associated with an Increased Risk of Incident Type 2 Diabetes in the Elderly.

OBJECTIVE: To investigate whether frailty is associated with an increased risk of incident type 2 diabetes mellitus (T2DM) in a prospective cohort of community-dwelling older people. DESIGN: Longitudinal study, mean follow-up of 4.4 years. SETTING: Progetto Veneto Anziani (Pro.V.A.) study that involved older community-dwellers. PARTICIPANTS: 1754 men and women older than 65 years without T2DM at baseline. MEASUREMENTS: Frailty status was defined according to Fried criteria and categorized as frailty (≥3 criteria), prefrailty (1-2 criteria), or no frailty (0 criterion). Incident T2DM was defined as fasting plasma glucose (FPG) ≥7.0 mmol/L, or glycosylated hemoglobin ≥6.5%, the use of glucose-lowering drugs, or FPG ≥11.1 mmol/L on a 2-hour oral glucose tolerance test during the follow-up. All T2DM diagnoses were confirmed by endocrinologists. RESULTS: At baseline, frail participants (n = 174) were significantly (a) more obese and had higher waist circumference, (b) experienced a higher rate of cardiovascular disease (including hypertension), and (c) presented with higher, but not pathologic, values of glycosylated hemoglobin and FPG than prefrail (n = 830) and nonfrail participants (n = 750). Over a 4.4-year follow-up, 265 individuals developed T2DM. In a logistic regression analysis, adjusted for potential baseline confounders, frailty [odds ratio (OR) = 1.87, 95% confidence interval (CI) = 1.31-2.13, P < .0001] and prefrailty (OR = 1.60, 95% CI = 1.27-2.00, P < .0001) were associated with a significantly higher incidence of T2DM than in nonfrail individuals. CONCLUSION: Among community-dwelling older people, frailty and prefrailty were significant and independent predictors of T2DM, which is a major and potentially preventable risk factor for multiple comorbidities.

What physical performance measures predict incident cognitive decline among intact older adults? A 4.4year follow up study.

Reductions in physical performance, cognitive impairment (CI) and decline (CD), are common in older age, but few prospective cohort studies have considered the relationship between these domains. In this study we investigated whether reduced physical performance and low handgrip/lower limbs strength, could predict a higher incidence of CI/CD during a 4-year follow-up among a cohort of elderly individuals. From 3099 older community-dwelling individuals initially enrolled in the Progetto Veneto Anziani (PRO.V.A.) study, 1249 participants without CI at the baseline were included (mean age 72.2years, 59.5% females). Physical performance measures included the Short Physical Performance Battery (SPPB), 4m gait speed, chair stands time, leg extension and flexion, handgrip strength, and 6-Minute Walking Test (6MWT), categorized in gender-specific tertiles. CI was defined as a Mini-Mental State Examination (MMSE) score below 24; CD a decline of 3 or more points in the MMSE without CI. At baseline, participants developing CI during follow-up scored significantly worse across all physical performance measures compared to those that retained normal cognitive status. After adjusting for potential confounders, a significant trend for MMSE changes was noted for all physical performance tests, except for the SPPB and chair stands time. Multinomial logistic regression revealed that slow gait speed at baseline significantly predicted CD at follow up. Poor SPPB performance and slower gait speed predicted the onset of CI at the follow-up. In conclusion, slow walking speed appears to be the best independent predictor of poor cognitive status over a 4.4-year follow-up, while other items of SPPB were also significantly associated with CI.

Serum dehydroepiandrosterone sulfate and osteoarthritis in older people: the Pro.V.A. study.

Although osteoarthritis (OA) and low levels of dehydroepiandrosterone sulfate (DHEAS) are common in the elderly, no studies on human beings are available concerning the possible relationship between them. We aimed to examine the relationship between DHEAS levels and any presence of OA in a cohort of community-dwelling older subjects. This study was part of the Progetto Veneto Anziani (Pro.V.A.), an Italian population-based cohort study on people over 65 years old. In this cross-sectional work, we considered 2050 individuals with a mean age of 74.2 ± 7.1 years (818 M and 1232 F), and with a complete set of information on OA and DHEAS levels. OA was defined using a standardized algorithm investigating disease history, medical records, symptoms, use of analgesic drugs for OA, and physical examination of the hand, hip, and knee. DHEAS levels were classified using gender-specific tertiles. OA at the three sites investigated was significantly more common in women than in men, and in individuals with lower serum DHEAS concentrations. On logistic regression analysis, taking those in the highest DHEAS tertile for reference and adjusting for potential confounders, subjects in the lowest tertile had significantly higher odds of OA involving the hand (men: OR = 1.49; 95 % CI 1.31-1.70, women: 1.28; 95 % CI 1.16-1.41), hip (men: 1.55; 95 % CI 1.33-1.81; women: 1.17; 95 % CI 1.06-1.30), and knee (men: 1.54; 95 % CI 1.35-1.76; women: 1.31 95 % CI 1.19-1.45). Similar findings emerged for individuals in the intermediate DHEAS tertile. Low DHEAS levels are associated with OA, irrespective of site and gender.

Low Hemoglobin Levels and the Onset of Cognitive Impairment in Older People: The PRO.V.A. Study.

Low hemoglobin (Hb) levels are attracting interest as a risk factor for cognitive impairment, but with contrasting evidence emerging from the current literature. The aim of our work was to investigate the relationship between baseline serum Hb levels and the incidence of cognitive impairment in older people over a follow-up of 4.4 years. Our study considered a sample of 1227 elderly subjects cognitively intact at baseline, enrolled under the Progetto Veneto Anziani (Pro.V.A.) among 3099 screened subjects. For all participants, we measured serum Hb levels on blood samples; incident cognitive impairment was defined as a Mini Mental State Examination (MMSE) score <24 and confirmed by geriatricians skilled in psychogeriatric medicine. No differences in baseline MMSE scores across Hb tertiles emerged in either gender. After the 4.4 years of follow-up, we identified 403 new cases of cognitive impairment (147 men and 256 women). Cox's regression analysis showed that participants with the lowest baseline Hb concentrations carried a significant 37% higher risk (95% confidence interval [CI]: 1.08-1.75; p = 0.01) of being diagnosed with cognitive impairment during the follow-up. Considering the gender separately, the risk of cognitive impairment only increased significantly, by 60%, for men in the lowest Hb tertile (95% CI: 1.06-2.41; p = 0.02), but not for women (hazard ratio = 1.32; 95% CI: 0.97-1.79; p = 0.08). In conclusion, low Hb concentrations may predict the onset of cognitive impairment in the elderly, apparently with a stronger association in men than in women.

Association of Osteoarthritis With Increased Risk of Cardiovascular Diseases in the Elderly: Findings From the Progetto Veneto Anziano Study Cohort.

OBJECTIVE: The possible relevance of osteoarthritis (OA) as a cardiovascular disease (CVD) risk factor is still debated. The aim of this study was to investigate the association between OA and the onset of CVD in older individuals. METHODS: Among a sample of 3,099 elderly subjects, 2,158 were identified as having no CVD at baseline and were followed up for a mean ± SD 4.4 ± 1.2 years. OA was defined using a standardized algorithm that investigated disease history, medical documentation (including radiographic reports), symptoms, and physical examination of the joints. Incident CVD was defined as the onset of coronary artery disease, heart failure, stroke/transient ischemic attack, peripheral artery disease, and CVD-related hospitalization or mortality. RESULTS: At baseline, 1,336 (61.9%) of the 2,158 study participants had OA. Participants with OA had more potential CVD risk factors, including obesity, hypertension, high levels of low-density lipoprotein, greater severity of inflammation, and worse renal function, than did those without OA. During the follow-up, 47.8% of the subjects with OA developed a new CVD event, compared to 41.3% of those without OA. Using an adjusted Cox regression analysis, the presence of OA significantly increased the risk of CVD (hazard ratio 1.22, 95% confidence interval 1.02-1.49; P = 0.04). The association between OA and CVD was stronger when the hip or knee was affected, and also was stronger in women than in men and when ≥2 joints were involved. Considering single CVD outcomes, the presence of OA significantly increased the risk of new coronary artery disease, heart failure, and hospitalization for CVD. CONCLUSION: OA may be a significant predictor of the onset of CVD in elderly individuals, particularly in women with OA and when OA affects the lower limbs or ≥2 joints are involved.