Jos P. C. M. van Campen

Gait stability and variability measures show effects of impaired cognition and dual tasking in frail people

BackgroundFalls in frail elderly are a common problem with a rising incidence. Gait and postural instability are major risk factors for falling, particularly in geriatric patients. As walking requires attention, cognitive impairments are likely to contribute to an increased fall risk. An objective quantification of gait and balance ability is required to identify persons with a high tendency to fall. Recent studies have shown that stride variability is increased in elderly and under dual task condition and might be more sensitive to detect fall risk than walking speed. In the present study we complemented stride related measures with measures that quantify trunk movement patterns as indicators of dynamic balance ability during walking. The aim of the study was to quantify the effect of impaired cognition and dual tasking on gait variability and stability in geriatric patients.MethodsThirteen elderly with dementia (mean age: 82.6 ± 4.3 years) and thirteen without dementia (79.4 ± 5.55) recruited from a geriatric day clinic, walked at self-selected speed with and without performing a verbal dual task. The Mini Mental State Examination and the Seven Minute Screen were administered. Trunk accelerations were measured with an accelerometer. In addition to walking speed, mean, and variability of stride times, gait stability was quantified using stochastic dynamical measures, namely regularity (sample entropy, long range correlations) and local stability exponents of trunk accelerations.ResultsDual tasking significantly (p < 0.05) decreased walking speed, while stride time variability increased, and stability and regularity of lateral trunk accelerations decreased. Cognitively impaired elderly showed significantly (p < 0.05) more changes in gait variability than cognitive intact elderly. Differences in dynamic parameters between groups were more discerned under dual task conditions.ConclusionsThe observed trunk adaptations were a consistent instability factor. These results support the concept that changes in cognitive functions contribute to changes in the variability and stability of the gait pattern. Walking under dual task conditions and quantifying gait using dynamical parameters can improve detecting walking disorders and might help to identify those elderly who are able to adapt walking ability and those who are not and thus are at greater risk for falling.

Drug-Drug Interactions in a Geriatric Outpatient Cohort Prevalence and Relevance

BackgroundThe prevalence of drug-drug interactions (DDIs) in a geriatric population may be high because of polypharmacy. However, wide variance in the clinical relevance of these interactions has been shown.ObjectivesTo explore whether adverse drug reactions (ADRs) as a result of DDIs can be identified by clinical evaluation, to describe the prevalence of ADRs and diminished drug effectiveness as a result of DDIs and to verify whether the top ten most frequent potential DDIs known to public pharmacies are of primary importance in geriatric outpatients in the Netherlands.MethodAll adverse events classified by the Naranjo algorithm as being a possible ADR and drug combinations resulting in diminished drug effectiveness were identified prospectively in 807 geriatric outpatients (mean age 81 years) at their first visit. The setting was a diagnostic day clinic. The Medication Appropriateness Index (MAI) and Beers criteria were used to evaluate drug use and identify possible DDIs. The ten most frequent potential interactions, according to a 1997 national database of public pharmacies (‘Top Ten’) in the Netherlands, and possible adverse events as a result of other interactions, were described. The effects of changes in medication regimen were recorded by checking the medical records.ResultsIn 300 patients (44.5% of the 674 patients taking more than one drug), 398 potential DDIs were identified. In 172 (25.5%) of patients taking more than one drug, drug combinations were identified that were responsible for at least one ADR or which possibly resulted in reduced effectiveness of therapy. Eighty-four of the 158 possible ADRs resulting from enhanced action of drugs forming combinations listed in the ‘Top Ten’ were seen in 73 patients. Only four DDIs resulting in less effective therapy that involved drug combinations in the ‘Top Ten’ were identified. Changes in drug regimens pertaining to possible interactions were proposed or put into effect in 111 of the 172 (65%) patients with possible DDIs. Sixty-one (55%) of these patients returned for follow-up. Of these, 49 (80%) were shown to have improved after changes were made to their medication regimen.ConclusionIn this study, nearly half of the geriatric outpatients attending a diagnostic day clinic who were taking more than one drug were candidates for DDIs. One-quarter of these patients were found to have possible adverse events or diminished treatment effectiveness that may have been at least partly caused by these DDIs. These potential interactions can be identified through clinical evaluation. In the majority of patients (99 of 172) the potential interactions resulting in possible ADRs or diminished effectiveness were not present in the ‘Top Ten’ interactions described by a national database of public pharmacies, a finding that emphasizes that the particular characteristics of geriatric patients (e.g. frequent psychiatric co-morbidities) need to be considered when evaluating their drug use. At least 7% of all patients taking more than one drug, and 80% of those with possible drug interactions whose drug regimen was adjusted, benefited from changes made to their drug regimens.

Reasons for undertreatment with oral anticoagulants in frail geriatric outpatients with atrial fibrillation: a prospective, descriptive study.

ObjectivesThe main aims of the study were to explore whether oral anti-coagulation (OAC) for atrial fibrillation (AF) in geriatric outpatients is prescribed in accordance with international (American College of Cardiology/American Heart Association/European Society of Cardiology [ACC/AHA/ESC]) and Dutch national guidelines for the general practitioner (GP) and to identify whether age and selected co-morbid conditions are associated with undertreatment. As a secondary objective, we wanted to establish how many patients discontinue OAC because of major bleeding.MethodsIn 2004, at the first visit of all patients to the geriatric day clinic of the Slotervaart Hospital in Amsterdam, the Netherlands, demographic data, Mini-Mental State Examination score, medical history, Charlson Comorbidity Index score, and data on medication use and changes were documented. The presence of AF was established by assessment of medical history information obtained by the GP, the history taken from patients and their caregivers, and the results of clinical evaluation, including ECG findings. Associations between the use of OAC, demographic data and co-morbid conditions registered in the Dutch NHG (Nederlands Huisartsen Genootschap [Dutch College of General Practitioners]) standard for GPs as risk factors for stroke or contraindications to the use of OAC were analysed. The reasons for discontinuing OAC were assessed after 4 years by requesting the information from the anticoagulation services or the GP.ResultsAt the time of the initial visit, 17.5% of the 807 outpatients had chronic AF (n= 135) or were known to have paroxysmal AF (n = 6). The mean age of the 141 patients in this cohort was 84.3 years (SD 6.2 years). Co-morbid conditions increasing the risk of stroke were present in 129 patients (91.5%). Contraindications to the use of OAC were observed in 118 patients (83.7%). Of the 116 patients with AF in their history before their visit, 57.8% were being treated with OAC at the time of their visit. After comprehensive geriatric assessment, 73 (51.8%) of the 141 patients with chronic or paroxysmal AF were continued on OAC. Of the 141 patients with chronic or paroxysmal AF, 110 (78.0%) had both extra stroke risk factors and contraindications to the use of OAC. Only increasing age was significantly and independently associated with not being prescribed anticoagulants (p<0.001). At the 4-year follow-up, OAC had been discontinued in 5.5% of patients because of major bleeding; three patients (4.1%) taking OAC had died as a result of major bleeding, and one other patient had discontinued treatment because of a major, non-lethal bleeding episode.ConclusionApplying the NHG standard for appropriate prescription, and disregarding age as a risk factor or contraindication, in this population, 14 of 141 patients (9.9%) were inappropriately prescribed OAC, salicylates or no prophylaxis. Since only patient age was associated with not prescribing OAC in this study, higher age still seems to be considered the most important contraindication to anticoagulation therapy. Implementation of better models for stratifying bleeding risk in the frail elderly is needed. After 4 years, the cumulative rate of bleeding causing discontinuation of anticoagulation therapy in this usual-care study of frail older patients was not alarmingly higher than in other usual-care studies.

Amyloid beta protein and tau in cerebrospinal fluid and plasma as biomarkers for dementia: a review of recent literature.

This review addresses recent developments in amyloid beta (Abeta), total tau (t-tau), and phosporylated tau (p-tau) protein analysis, in cerebrospinal fluid (CSF) and plasma as biomarkers for dementia. Recent research focused on the protection of patients with mild cognitive impairment (MCI) into dementia and the differential diagnosis of Alzheimers Disease (AD). A combination of Abeta42 and t-tau in CSF can discriminate between patients with stable MCI and patients with progressive MCI into AD or other types of dementia with a sufficient sensitivity and specificity. Regression analyses demonstrated that pathological CSF (with decreased Abeta42 and and increased tau levels) is a very strong predictor for the progression of MCI into AD. Furthermore, CSF measurements of p-tau and Abeta42 can assist in diagnosing vascular dementia or frontotemporal dementia in the differential diagnosis of AD indicated by a reasonable sensitivity and specificity. Whether tau in combination with Abeta42 or in combination with the Abeta37/Abeta42 or Abeta38/Abeta42 ratio aids in the discrimination between AD and Lewy Body dementia remains to be elucidated. Cross-sectional research could not demonstrate significant differences for Abeta40 and Abeta42 in plasma between AD and controls. However, a recently published longitudinal study showed high baseline Abeta40 levels, especially when combined with low baseline Abeta 42 levels, are a strong risk factor for the development of dementia. This emphasizes the importance of performing longitudinal studies in addition to cross-sectional ones. The origin of plasma Abeta and its transport between CSF and plasma, however, needs further clarification. In conclusion, progress has been made regarding Abeta and tau as biomarkers for dementia, both for differentiation between stable MCI and progressive MCI patients and for the differential diagnosis of AD. Future research should aim to validate these recently published results, preferably in pathologically confirmed AD patients. In addition, it is important to standardise research in terms of study design (longitudinal, minimal follow-up period of 5 years), type of researched parameters ( total or p-tau, type of Abeta peptides), type of matrix (CSF and plasma) and data analysis (establishment of predefined cut-off values, type of ratio, type of marker combination).

Discrepancies in reported drug use in geriatric outpatients: relevance to adverse events and drug-drug interactions.

BACKGROUND Increased age is associated with polypharmacy. Polypharmacy is a risk factor for severe adverse drug reactions (ADRs) and is associated with an increased risk of mortality. OBJECTIVES The main goal of the current study was to describe the frequency and relevancy of discrepancies in drug use in Dutch geriatric outpatients as reported by the patients and their caregivers, documented by the referring general practitioner (GP), and registered by the public pharmacy. The frequency of medication discrepancy adverse patient events (MDAPEs) was also recorded. In addition, possible contributing factors-such as increasing age, cognitive status and depressive symptoms, the number of medications used, the number of physicians visited by the patient, and the presence of a caregiver to supervise medication use-were studied. METHODS This was a prospective descriptive study conducted at the geriatric outpatient clinic of a teaching hospital. Between January 1 and May 1, 2005, consecutive patients were included if they were aged >65 years, reported use of > or =1 medication, and if they could understand the goals and consequences of participating in the study. The medications described by geriatric patients and their caregivers were compared with the drugs listed by their GP. The pharmacies of the referred patients were asked to send a description of the drugs distributed in the 6 months preceding the patients visit to the geriatric outpatient clinic. The classification of ADRs and undertreatment as clinically relevant was done by study investigators who were blinded for the presence of discrepancy. RESULTS A total of 120 outpatients were included. The mean (SD) age of the study patients was 82.3 (6.8) years; 71.7% were women. Of the 120 patients, 113 patients (94.2%) reported taking >1 drug and 88 (73.3%) were prescribed > or =4 drugs. At least 1 discrepancy between the medication lists of the patients, GP, or pharmacy was present in 104 of the 120 patients (86.7%). In 90 patients (75.0%), there was > or =1 discrepancy between the medication reported by the patient and the GP. Patients with > or =1 discrepancy reported taking a higher mean number of drugs and had more prescribing physicians in addition to their GP. Twenty-nine patients (24.2%) experienced an MDAPE involving the use of drugs the GP had not correctly described in the letter of referral. The pharmacy was unaware of the use of medication involved in an MDAPE in 2 patients. CONCLUSIONS Geriatricians should assume that the medication lists supplied by GPs are incomplete or incorrect, and be aware that in approximately 25% of patients, symptoms may be caused by medication use inaccurately described in the referral. Reports by the community pharmacy may supply valuable additional information. Because there are also discrepancies between patients and pharmacies, medication use from a database-with data from prescribing physicians and pharmacy systems-will still have to be confirmed by the patient.

The Effects of Fall-Risk-Increasing Drugs on Postural Control: A Literature Review

Meta-analyses showed that psychotropic drugs (antidepressants, neuroleptics, benzodiazepines, antiepileptic drugs) and some cardiac drugs (digoxin, type IA anti-arrhythmics, diuretics) are associated with increased fall risk. Because balance and gait disorders are the most consistent predictors of future falls, falls due to use of these so-called fall-risk-increasing drugs (FRIDs) might be partly caused by impairments of postural control that these drugs can induce. Therefore, the effects of FRIDs on postural control were examined by reviewing literature. Electronic databases and reference lists of identified papers were searched until June 2013. Only controlled research papers examining the effects of FRIDs on postural control were included. FRIDs were defined according to meta-analyses as antidepressants, neuroleptics, benzodiazepines, antiepileptic drugs, digoxin, type IA anti-arrhythmics, and diuretics. Ninety-four papers were included, of which study methods for quantifying postural control, and the effects of FRIDs on postural control were abstracted. Postural control was assessed with a variety of instruments, mainly evaluating aspects of body sway during quiet standing. In general, postural control was impaired, indicated by an increase in parameters quantifying body sway, when using psychotropic FRIDs. The effects were more pronounced when people were of a higher age, used psychotropics at higher daily doses, with longer half-lives, and administered for a longer period. From the present literature review, it can be concluded that psychotropic drugs cause impairments in postural control, which is probably one of the mediating factors for the increased fall risk these FRIDs are associated with. The sedative effects of these drugs on postural control are reversible, as was proven in intervention studies where FRIDs were withdrawn. The findings of the present literature review highlight the importance of using psychotropic drugs in the older population only at the lowest effective dose and for a limited period of time.

Walking ability to predict future cognitive decline in old adults: A scoping review.

Early identification of individuals at risk for cognitive decline may facilitate the selection of those who benefit most from interventions. Current models predicting cognitive decline include neuropsychological and/or biological markers. Additional markers based on walking ability might improve accuracy and specificity of these models because motor and cognitive functions share neuroanatomical structures and psychological processes. We reviewed the relationship between walking ability at one point of (mid) life and cognitive decline at follow-up. A systematic literature search identified 20 longitudinal studies. The average follow-up time was 4.5 years. Gait speed quantified walking ability in most studies (n=18). Additional gait measures (n=4) were step frequency, variability and step-length. Despite methodological weaknesses, results revealed that gait slowing (0.68-1.1 m/sec) preceded cognitive decline and the presence of dementia syndromes (maximal odds and hazard ratios of 10.4 and 11.1, respectively). The results indicate that measures of walking ability could serve as additional markers to predict cognitive decline. However, gait speed alone might lack specificity. We recommend gait analysis, including dynamic gait parameters, in clinical evaluations of patients with suspected cognitive decline. Future studies should focus on examining the specificity and accuracy of various gait characteristics to predict future cognitive decline.

A flexed posture in elderly patients is associated with impairments in postural control during walking

A flexed posture (FP) is characterized by protrusion of the head and an increased thoracic kyphosis (TK), which may be caused by osteoporotic vertebral fractures (VFs). These impairments may affect motor function, and consequently increase the risk of falling and fractures. The aim of the current study was therefore to examine postural control during walking in elderly patients with FP, and to investigate the relationship with geriatric phenomena that may cause FP, such as increased TK, VFs, frailty, polypharmacy and cognitive impairments. Fifty-six elderly patients (aged 80 ± 5.2 years; 70% female) walked 160 m at self-selected speed while trunk accelerations were recorded. Walking speed, mean stride time and coefficient of variation (CV) of stride time were recorded. In addition, postural control during walking was quantified by time-dependent variability measures derived from the theory of stochastic dynamics, indicating smoothness, degree of predictability, and local stability of trunk acceleration patterns. Twenty-five patients (45%) had FP and demonstrated a more variable and less structured gait pattern, and a more irregular trunk acceleration pattern than patients with normal posture. FP was significantly associated with an increased TK, but not with other geriatric phenomena. An increased TK may bring the bodys centre of mass forward, which requires correcting responses, and reduces the ability to respond on perturbation, which was reflected by higher variation in the gait pattern in FP-patients. Impairments in postural control during walking are a major risk factor for falling: the results indicate that patients with FP have impaired postural control during walking and might therefore be at increased risk of falling.

Evaluation of Pharmacotherapy in Geriatric Patients after Performing Complete Geriatric Assessment at a Diagnostic Day Clinic

AbstractBackground: Elderly patients often take multiple drugs. It is known that polypharmacy, i.e. use of five or more drugs, may lead to drug interactions and adverse events. However, undertreatment of conditions or illnesses is also a concern in geriatric patients. A centralised review of both diagnoses and medication may play a key role in optimising pharmacotherapy in geriatric patients. The aims of this study were to evaluate the quality and appropriateness of medication after performing a complete geriatric assessment (CGA) and medication review at a diagnostic geriatric day clinic, to investigate reasons for drug changes, and to determine whether medication review leads to a reduction in the number of drugs used. Methods: A chart review was performed in 702 patients (mean age 82.0 years, range 57.1–104.1 years) who underwent a CGA at a diagnostic geriatric day clinic. Medication at admission, changes in medication and reasons for changes were noted. Results: Vitamins, for example folic acid and vitamin B12 (cyanocobalamin), and trimethoprim for urinary tract infections were the most frequently started medications after CGA and medication review. The number of drugs used was reduced in only a minority of patients (11.7%); reasons for discontinuation were a diagnosis that was no longer relevant (38.8%), adverse events (33.2%) and identification of better pharmacotherapeutic options (22.0%). In 69.2% of the cases a new diagnosis was the reason for starting a new medication, followed by osteoporosis prophylaxis (15.0%) and improvement in pharmacotherapy (10.6%). At admission, patients were taking a mean number of 4.6 drugs (range 0–17). A mean of 0.8 drugs (range from reduction of 5 to addition of 7) had been added per patient, resulting in a mean number of 5.4 (range 0–18) prescribed drugs at discharge. Conclusion: Evaluation of medication in patients after performing CGA at the geriatric day clinic investigated resulted in relevant medication changes. The main reason for prescribing new drugs was a new diagnosis. Absence of a relevant medical indication was the main reason for stopping drugs. CGA and medication review resulted in a mean net addition of 0.8 drugs per patient.

Changes in Under-Treatment after Comprehensive Geriatric Assessment An Observational Study

AbstractBackground Under-treatment is frequently present in geriatric patients. Because this patient group often suffer from multiple diseases, polypharmacy (defined as the concomitant chronic use of five or more drugs) and contraindications to indicated drugs may also frequently be present. Objective To describe the prevalence of under-treatment with respect to frequently indicated medications before and after comprehensive geriatric assessment (CGA) and the prevalence of contraindications to these medications. Patients and Methods The geriatric outpatients evaluated in this study had previously been included in a prospective descriptive study conducted in 2004. Demographic data, medical history, co-morbidity and medication use and changes were documented. The absence of drugs indicated for frequently under-treated conditions before and after CGA was compared. Under-treatment was defined as omission of drug therapy indicated for the treatment or prevention of 13 established diseases or conditions known to be frequently under-treated. Co-morbid conditions were independently classified by two geriatricians, who determined whether or not a condition represented a contraindication to use of these drugs. Results In 2004, 807 geriatric outpatients were referred for CGA. Of these, 548 patients had at least one of the 13 selected diseases or conditions. Thirty-two of these patients were excluded from the analysis, leaving 516 patients. Before CGA, 170 of these patients were under-treated (32.9%); after CGA, 115 patients (22.3%) were under-treated. Contraindications were present in 102 of the patients (19.8%) and were more frequent in under-treated patients. After CGA, mean drug use and the prevalence of polypharmacy increased. Although 393 drugs were discontinued after CGA, the overall number of drugs used increased from 3177 before CGA to 3424 after CGA. Five times more drugs were initiated for a new diagnosis than for correction of under-treatment. Conclusions Under-treatment is significantly reduced after CGA. Patients with contraindications to indicated medicines are more frequently under-treated. CGA leads to an increase in polypharmacy, mainly because of new conditions being diagnosed and despite frequent discontinuation of medications.