Background: Clinical diagnosis of Alzheimer’s disease (AD) increasingly incorporates CSF biomarkers. However, due to the intrinsic variability of the immunodetection techniques used to measure these ...biomarkers, establishing in-house cutoffs defining the positivity/negativity of CSF biomarkers is recommended. However, the cutoffs currently published are usually reported by using cross-sectional datasets, not providing evidence about its intrinsic prognostic value when applied to real-world memory clinic cases. Methods: We quantified CSF Aβ1-42, Aβ1-40, t-Tau, and p181Tau with standard INNOTEST® ELISA and Lumipulse G® chemiluminescence enzyme immunoassay (CLEIA) performed on the automated Lumipulse G600II. Determination of cutoffs included patients clinically diagnosed with probable Alzheimer’s disease (AD, n = 37) and subjective cognitive decline subjects (SCD, n = 45), cognitively stable for 3 years and with no evidence of brain amyloidosis in 18F-Florbetaben-labeled positron emission tomography (FBB-PET). To compare both methods, a subset of samples for Aβ1-42 (n = 519), t-Tau (n = 399), p181Tau (n = 77), and Aβ1-40 (n = 44) was analyzed. Kappa agreement of single biomarkers and Aβ1-42/Aβ1-40 was evaluated in an independent group of mild cognitive impairment (MCI) and dementia patients (n = 68). Next, established cutoffs were applied to a large real-world cohort of MCI subjects with follow-up data available (n = 647). Results: Cutoff values of Aβ1-42 and t-Tau were higher for CLEIA than for ELISA and similar for p181Tau. Spearman coefficients ranged between 0.81 for Aβ1-40 and 0.96 for p181TAU. Passing–Bablok analysis showed a systematic and proportional difference for all biomarkers but only systematic for Aβ1-40. Bland–Altman analysis showed an average difference between methods in favor of CLEIA. Kappa agreement for single biomarkers was good but lower for the Aβ1-42/Aβ1-40 ratio. Using the calculated cutoffs, we were able to stratify MCI subjects into four AT(N) categories. Kaplan–Meier analyses of AT(N) categories demonstrated gradual and differential dementia conversion rates (p = 9.815−27). Multivariate Cox proportional hazard models corroborated these findings, demonstrating that the proposed AT(N) classifier has prognostic value. AT(N) categories are only modestly influenced by other known factors associated with disease progression. Conclusions: We established CLEIA and ELISA internal cutoffs to discriminate AD patients from amyloid-negative SCD individuals. The results obtained by both methods are not interchangeable but show good agreement. CLEIA is a good and faster alternative to manual ELISA for providing AT(N) classification of our patients. AT(N) categories have an impact on disease progression. AT(N) classifiers increase the certainty of the MCI prognosis, which can be instrumental in managing real-world MCI subjects.
Optical coherence tomography angiography (OCT-A) allows the detection of retinal vessel density (VD) loss, which is a reflection of brain vascular pathology. We aimed to investigate differences in ...macular VD in the superficial plexus in a large cohort of individuals cognitively unimpaired (CU), with mild cognitive impairment due to Alzheimer´s disease (MCI-AD), MCI due to cerebrovascular pathology (MCI-Va), probable Alzheimer´s disease dementia (ADD) and Vascular Dementia (VaD). Clinical, demographical, ophthalmological and OCT-A data from the Neuro-ophthalmology Research at Fundació ACE (NORFACE) project were analyzed. Differences of macular VD in four quadrants (superior, nasal, inferior and temporal) among the five diagnostic groups were assessed in a multivariate regression model, adjusted by age, sex, education, hypertension, diabetes mellitus, heart disease and stroke. The study cohort comprised 672 participants: 128 CU, 120 MCI-AD, 111 MCI-Va, 257 ADD and 56 VaD. Regression analysis showed a significantly higher VD in the temporal quadrant in MCI-AD compared to CU participants (49.05 ± 4.91 vs 47.27 ± 4.17, p = 0.02, d = 0.40), and a significantly lower VD in the inferior quadrant in MCI-Va compared to CU participants (48.70 ± 6.57 vs 51.27 ± 6.39, p = 0.02, d = 0.40). Individuals with heart disease presented significantly lower VD in the inferior quadrant than those without (p = 0.01). The interaction of sex and diagnosis had no effect in differentiating VD. Mini-Mental State Examination (MMSE) scores were not correlated to VD (all r < 0.16; p > 0.07). In conclusion, our study showed that the MCI-AD and MCI-Va groups had significant differences in macular VD in opposite directions in the temporal and inferior quadrants, respectively, compared to CU participants, suggesting that macular VD might be able to differentiate two pathogenic pathways (AD- and cerebrovascular-related) in early stages of cognitive decline.
Older adults' perception of their own risk of fall has never been included into screening tools. The goal of this study was to evaluate the predictive validity of questions on subjects' ...self-perception of their own risk of fall.
This prospective study was conducted on a probabilistic sample of 772 Spanish community-dwelling older adults, who were followed-up for a one year period. At a baseline visit, subjects were asked about their recent history of falls (question 1: "Have you fallen in the last 6 months?"), as well as on their perception of their own risk of fall by using two questions (question 2: "Do you think you may fall in the next few months?" possible answers: yes/no; question 3: "What is the probability that you fall in the next few months?" possible answers: low/intermediate/high). The follow-up consisted of quarterly telephone calls, where the number of falls occurred in that period was recorded.
A short questionnaire built with questions 1 and 3 showed 70% sensitivity (95% CI: 56%-84%), 72% specificity (95% CI: 68%-76%) and 0.74 area under the ROC curve (95% CI: 0.66-0.82) for prediction of repeated falls in the subsequent year.
The estimation of one's own risk of fall has predictive validity for the occurrence of repeated falls in older adults. A short questionnaire including a question on perception of one's own risk of fall and a question on the recent history of falls had good predictive validity.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Recurrent falls represent a priority in geriatric research. In this study we evaluated the influence of pain as a risk factor for recurrent falls (two or more in 1 year) in the older (65-79 years) ...and oldest-old (80 or more years) non-institutionalized population.
Prospective cohort study. 772 non-institutionalized individuals with ages of 65 years or older (with overrepresentation of people aged 80 years or older n = 550) were included through randomized and multistage sampling, stratified according to gender, geographic area and habitat size. Basal evaluation at participant's home including pain evaluation by Face Pain Scale (FPS, range 0-6) and then telephonic contact every 3 months were performed until complete 12 months. Multivariate analysis by logistic regression (recurrent falls as outcome variable) for each age group (older and oldest-old group) were developed considering pain as a quantitative variable (according to FPS score). Models were adjusted for age, gender, balance, muscle strength, depressive symptoms, cognitive decline, number of drugs and number of drugs with risk of falls.
114 (51.35%) and 286 (52%) participants of older and oldest-old group, respectively, reported pain; and recurrent falls occurred in 6.93% (n = 12) of the older group and 12.06% (n = 51) of the oldest-old group. In the older group, pain was associated with recurrent falls, with an associated odds ratio (OR) of 1.47 (95% CI 1.08-2.00; beta 0.3864) for each unit increase in pain intensity (thus, participants with the most severe pain FPS 6 had OR of 10.16 regarding to participants without pain FPS 0). In the oldest-old group, pain was not associated with recurrent falls.
Pain, a potentially modifiable and highly prevalent symptom, is a risk factor for recurrent falls in the older people (65-79 years). However, we have not been able to demonstrate that this relationship is maintained in the oldest-old population (80 or more years).
Objectives. Low blood pressure (BP) has been proposed as a risk factor of death in elderly patients. However, this association could be partially accounted for by the deleterious effects of ...BP-lowering drugs. We analyzed whether these drugs are associated to an increased risk of death in elderly patients taking multiple potential confounders into account. Design. This is a prospective cohort study. Setting and Participants. Probabilistic sample of 772 community-dwelling patients aged >65 years living in Spain, who were appointed for an initial clinical visit and followed up through telephone calls 4, 6, 9, 12, and 60 months afterwards. Methods. At baseline visit, BP was measured using standardized methods, and BP medications and risk factors of death in elderly patients (BMI, oxygen saturation, toxic habits, comorbidity, muscular strength, and functional and cognitive capacity) were collected. During the follow-up, the vital status of patients and the date of death were ascertained. Results. During a median 5-year follow-up, 226 all-cause deaths occurred among the 686 participants included in the analysis. In a Cox regression model that included all the BP drug classes, diuretics and nitrites were significantly associated with mortality (p<0.005). Within diuretics, furosemide was found to be responsible for the association of the group. In multivariable Cox regression models adjusted for BP and the rest of the mortality risk factors, furosemide remained as the only BP drug that was independently associated with mortality (hazard ratio 2.34; p<0.01). Conclusions. Furosemide was prospectively associated with increased mortality in older people. If confirmed, this drug should be taken into account by prescribers and considered a confounder in BP studies.
Background
In Europe, there is no conclusive data at national level about pain prevalence in non-institutionalized very old population. In USA, it has recently been reported a high prevalence (56 %); ...however, this data can not be extrapolated to other regions because the known influence of geographical and ethnic differences. Furthermore there are few data on use of treatments for pain in this population.
Aims
To explore prevalence and considered pharmacological treatments for pain in this population.
Methods
Transversal study on 551 participants aged 80 or more living in Spain (non-institutionalized). Probabilistic multistage sampling was carried out, stratified by sex and place of residence. All Spanish regions were considered for recruitment process. Pain (last 4 weeks), intensity (Face Pain Scale), localization and pharmacological treatments were evaluated by in-person interviews.
Results
Pain’s prevalence was 52.5 % (CI 95 % 48.28–56.80) and 38.5 % experienced pain of at least moderate intensity. The most frequently involved body regions were lower limbs (26.6 %) and dorso-lumbar region (21.9 %). Only 40 % of participants with pain and 43.2 % with moderate or severe pain used analgesics, and paracetamol was less frequently used than non-steroidal anti-inflammatory drugs at any pain intensity. Age was not associated with higher prevalence odds ratios 0.97 (CI 95 % 0.93–1.02) in females and 0.99 (CI 95 % 0.92–1.06) in males.
Conclusions
The prevalence of pain in non-institutionalized very old people is high. Pain is probably being undertreated, even moderate or severe pain. Guideline’s recommendations are probably not being considered to select the analgesic therapy.
Objective
Given the impact of recurrent falls in older people, risk evaluation for falling is an important part of geriatric assessment. Available clinical tools usually do not include patients’ ...self-perceived risk of falling. The objective of this study was to evaluate association with and predictive capacity of self-perceived risk of falling in recurrent falls.
Methods
Prospective cohort study. Patients attending a geriatric outpatients’ clinic were recruited (Pfeiffer score <5). A baseline assessment and follow-up over 14 months was scheduled for each patient. Self-perceived risk of falling was assessed through four questions. Association with falls was evaluated through relative risk, survival curves (Kaplan–Meier), and Cox regression (recurrent falls as outcome variables). Predictive capacity was evaluated through sensitivity, specificity, and predictive values.
Results
52 participants answered all 4 questions, and 15 participants (27.2 %) presented recurrent falls. Question 1 (Do you think you may fall in the next few months?) was associated with the occurrence of recurrent falls according to relative risk 3.88 (CI95 %:1.48–10.09) and survival curves (log Rank,
p
0.004). Such relationship is maintained over time. Cox-regression also showed significant difference in relation to the answer for question 1 and recurrent falls hazard ratio 4.044 (CI: 1.410–11.597);
p
0.009. Sensitivity, specificity, positive and negative predictive values (question 1) were 53.3 % (CI95 %:28.1–78.6), 84.2 % (CI95 %:72.6–95.8), 57.1 % (CI95 %:31.2–83.1), and 82.1 % (CI95 %:70.0–94.1), respectively.
Conclusions
Patients’ self-perceived risk of falling is related to recurrent falls amongst people with a high risk of falling and this parameter might be useful in falling risk evaluation.
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