Cerebrovascular disease and gait and balance impairment in mild to moderate Alzheimer’s disease

Objectives

Gait and movement abnormalities are traditionally considered infrequent in patients with mild/moderate Alzheimer’s disease (AD). However, an increased risk of falls and gait abnormalities has been detected, even in early stages of the disease. Whether these abnormalities are associated with cerebrovascular disease, which has a high prevalence in AD, remains unclear.

Design

Cross-sectional study.

Setting

Dementia outpatient clinics.

Participants

24 mild/moderate AD patients with (AD+CVD) and 20 without (AD-CVD) cerebrovascular disease without a history of stroke and antipsychotic medications.

Measurements

Physical performance, measured with the Short Physical Performance Battery [SPPB], a summary measure combining 4-meter gait speed, balance and muscle strength, and with 8-meter gait speed with a turn was compared between the two groups.

Results

AD+CVD patients showed a significant higher prevalence of 4-meter gait speed slower than 0,8 m/s (37.5% Vs 5%, p-value=0.01) and balance impairment (37.5% Vs 10%, p-value=0.038), as well as a slower 8-meter gait speed with a turn (mean+SD=0.6±0.2 Vs 0.8±0.2, p-value=0.024). These associations were confirmed in multivariable models. No differences were observed for muscle strength.

Conclusion

In our sample, AD with cerebrovascular disease had worse gait and balance than AD without cerebrovascular disease. If confirmed, these results may have clinical implications, since cerebrovascular disease can be potentially prevented.     

Severe impairment of circadian rhythm in Alzheimer’s disease

Circadian rhythmicity was repeatedly determined in a patient with Alzheimer??s disease by measuring his core temperature with a rectal thermistor and motor activity by an ambulatory activity monitor. The first recording, performed 9 years after he was diagnosed with Alzheimer??s disease, showed well organized 24 hr circadian rhythm of core body temperature. The second recording, made four months later, showed very poor fit of core body temperature to 24 hour rhythm, but excellent fit with 36 hour rhythm. The third recording, made two months later, showed again good fit of core body temperature with 24 hour cycle. The last recording, which was performed 5 months later, showed almost complete disappearance of circadian rhythm of body temperature. These changes probably reflect gradual lengthening of the circadian cycle that at one point became extremely lengthened before returning to the 24 hr cycle.     

Disease progression and costs of care in Alzheimer’s disease patients treated with donepezil: a longitudinal naturalistic cohort

Background/Aims

Improved data and methods are needed for modeling disease progression in Alzheimer’s disease (AD) for economic evaluation of treatments. The aim is to estimate prediction models for long-term AD progression and subsequently economic outcomes.

Methods

Three-year follow-up data on 435 patients treated with the cholinesterase inhibitor donepezil in clinical practise were analyzed. Regression models were estimated for long-term prediction of decline in cognitive function (ADAS-cog) and activities in daily living (ADL) ability, risk of institutionalization and costs of care.

Results

The cognitive deterioration was estimated at between 1.6 and 4 ADAS-cog points per every 6?months, increasing with disease severity. Cognitive function was an important predictor of ADL-ability, which itself was the most important predictor of the risk of institutionalization and costs of care. Combining all models in a cross-validation process generated accurate predictions of costs of care at each 6?months follow-up.

Conclusion

The proposed methods for representing AD progression and economic outcomes can be used in micro-simulation models for the economic evaluation of new treatments.     

Analysis of burden in caregivers of people with Alzheimer’s disease using self-report and supervision hours

Objectives

This study aimed to describe the baseline characteristics of informal carers of community-living Alzheimer’s disease (AD) patients by AD severity group and to identify factors associated with two measures of caregiver burden.

Design and setting

GERAS is a prospective observational study in France, Germany, and the UK, designed to assess costs and resource use associated with AD, for patients and their caregivers, stratified by disease severity.

Participants

1497 community-dwelling AD patients and their primary caregivers.

Measurements

Subjective caregiver burden assessed using the Zarit Burden Interview [ZBI] and time spent supervising patients (an objective measure of burden recorded using the Resource Utilization in Dementia instrument) during the month before the baseline visit were recorded. Separate multiple linear regression analyses using ZBI total score and caregiver supervision time as dependent variables were performed to identify patient and caregiver factors independently associated with caregiver burden.

Results

Increasing AD severity was associated with both subjective caregiver burden (ZBI total score) and overall caregiver time, which includes supervision time (both p<0.001, ANOVA). Better patient functioning (on instrumental activities of daily living) was independently associated with both a lower ZBI total score and less supervision time, whereas higher levels of caregiver distress due to patient behavior were associated with greater caregiver burden. Other factors independently associated with an increased ZBI total score included younger caregiver age, caregiver self-reported depression, caring for a male patient, and longer time since AD diagnosis. Caregivers living with the patient, being a male caregiver, patient living in a rural location, higher patient behavioral problem subdomain scores for apathy and psychosis, more patient emergency room visits, not receiving food delivery and receiving financial support for caregiving were all associated with greater caregiver supervision time.

Conclusion

Our results show that subjective caregiver burden and caregiver time are influenced by different factors, reinforcing the need to consider both aspects of caregiving when trying to minimize the burden of AD. However, interventions that minimize caregiver distress and improve patient functioning may impact on both subjective and objective burden.     

Nutritional and psycho-functional status in elderly patients with Alzheimer’s disease

Objectives  

Analysis of variations of nutritional status in relation to psycho-functional conditions in elderly patients with mild to moderate Alzheimer’s disease (AD) by means of bioelectrical impedance vector analysis (BIVA).     

Ghrelin and leptin secretion in patients with moderate Alzheimer’s disease

Background

Weight loss is a characteristic finding of patients with Alzheimer??s disease (AD). It seems that precedes cognitive impairment by some years, but the underlying causes are not fully understood. Ghrelin and leptin are involved in energy homeostasis, and may be implicated in weight losing observed in these patients.

Objective

To examine the potential relationship between ghrelin and leptin levels and weight loss in patients with AD.

Design

The study included 27 patients (10 men and 17 women) with AD of moderate severity, and 23 controls (10 males and 13 females), matched for age and BMI. Body fat and lean mass content were assessed using a portable apparatus. Cognitive function was assessed with the Mini-Mental State Examination. Basal serum samples for the measurement of leptin, ghrelin, insulin and glucose were obtained, and serum ghrelin, insulin and glucose were measured after a 75-gr glucose load in both groups.

Results

Patients with Alzheimer Disease (AD) have lower lean mass content compared to controls. Basal ghrelin and leptin is similar in patients with AD and controls. The area-under-the-curve for ghrelin (AUC) is lower in male patients with AD compared to control males, while no difference was observed between females AD and controls.

Conclusion

Male patients with AD, in contrast with female patients, fail to maintain a normal energy homeostasis even in the early stages of the disease, as shown by the decreased lean mass content in males AD compared to controls. Disruption of the normal compensatory modulation of ghrelin secretion might contribute to the metabolic changes observed in male patients with AD.     

Determinants of time to institutionalisation and related healthcare and societal costs in a community-based cohort of patients with Alzheimer’s disease dementia

Objectives

To examine the costs of caring for community-dwelling patients with Alzheimer’s disease (AD) dementia in relation to the time to institutionalisation.

Methods

GERAS was a prospective, non-interventional cohort study in community-dwelling patients with AD dementia and their caregivers in three European countries. Using identified factors associated with time to institutionalisation, models were developed to estimate the time to institutionalisation for all patients. Estimates of monthly total societal costs, patient healthcare costs and total patient costs (healthcare and social care together) prior to institutionalisation were developed as a function of the time to institutionalisation.

Results

Of the 1495 patients assessed at baseline, 307 (20.5%) were institutionalised over 36 months. Disease severity at baseline [based on Mini-Mental State Examination (MMSE) scores] was associated with risk of being institutionalised during follow up (p < 0.001). Having a non-spousal informal caregiver was associated with a faster time to institutionalisation (944 fewer days versus having a spousal caregiver), as was each one-point worsening in baseline score of MMSE, instrumental activities of daily living and behavioural disturbance (67, 50 and 30 fewer days, respectively). Total societal costs, total patient costs and, to a lesser extent, patient healthcare-only costs were associated with time to institutionalisation. In the 5 years pre-institutionalisation, monthly total societal costs increased by more than £1000 (€1166 equivalent for 2010) from £1900 to £3160 and monthly total patient costs almost doubled from £770 to £1529.

Conclusions

Total societal costs and total patient costs rise steeply as community-dwelling patients with AD dementia approach institutionalisation.

     

Being in control of Parkinson’s disease: A qualitative study of community-dwelling patients’ coping with changes in care

Background: Chronically ill patients have to cope with transfers in the level or setting of care. Patients with prevalent disorders such as diabetes mellitus can be supported by their general practitioner (GP) when experiencing such care changes, as the GP already offers them disease-specific care. For community-dwelling patients with low-prevalent diseases such as Parkinson’s disease (PD) – for which disease-specific care is provided by medical specialists – tailoring support to handle care changes requires more insight into patients’ coping.

Objectives: To explore PD patients’ coping with care changes.

Methods: A qualitative interview study was performed in 2013–2015 with a purposive sample of 16 community-dwelling PD patients in the Netherlands. A research assistant visited patients every month to explore if they had experienced a care change. If so, patients were interviewed face-to-face. An inductive approach to comparative content analysis was used.

Results: Patients encountered a variety of care changes such as changes in the level of unpaid care, the purchase of tools, modification of pharmacotherapy or admission to hospital. Being able to anticipate, initiate and independently handle care changes contributes to patients’ sense of control and acceptance of the post-change situation. Patients, who commenced care changes themselves, had more realistic expectations of it.

Conclusion: Community-dwelling PD patients seem to be able to cope with the care changes they face. Offering education to facilitate their anticipation and initiation of changes in care and their ability to act independently, can contribute to patients’ wellbeing. GPs can play a role in this.     

Cardiometabolic factors and disease duration in patients with Parkinson’s disease

ObjectivePrevious studies have reported that patients with Parkinson’s disease (PD) have a favorable cardiometabolic risk profile. The aim of this study was to investigate the relationship between cardiometabolic risk factors and the duration of disease.MethodsOne hundred and fifty patients with PD (56.7% men) were studied, measuring body mass index (BMI), waist circumference (WC), body fat percentage (BF%) by impedance, fasting glucose, serum lipids, and transaminases.ResultsIn sex- and age-adjusted correlation models, duration of PD was inversely related to BMI (r = ?0.20; P < 0.05) and BF% (r = ?0.29; P < 0.005). Using multivariable regression models (adjustments: age, gender, smoking status, levodopa dose and, alternatively, BMI, WC, or BF%), high-density lipoprotein (HDL) levels were positively correlated with disease duration (P < 0.01 for all). In models adjusted for WC and BF%, total HDL-cholesterol ratio was also inversely associated with duration of PD (P < 0.05 for both). No other association between biochemical variables and the duration of PD was found. Moreover, no dose–response effect of levodopa on metabolic risk factors was observed.ConclusionsHDL levels and total HDL-cholesterol ratio were favorably associated with duration of PD. This factor may contribute to cardiometabolic protection in PD. The mechanisms underlying this association deserve further investigation.     

The impact of memantine in combination with acetylcholinesterase inhibitors on admission of patients with Alzheimer’s disease to nursing homes: cost-effectiveness analysis in France

The costs associated with the care of Alzheimer’s disease patients are very high, particularly those associated with nursing home placement. The combination of a cholinesterase inhibitor (ChEI) and memantine has been shown to significantly delay admission to nursing homes as compared to treatment with a ChEI alone. The objective of this cost-effectiveness analysis was to evaluate the economic impact of the concomitant use of memantine and ChEI compared to ChEI alone. Markov modelling was used in order to simulate transitions over time among three discrete health states (non-institutionalised, institutionalised and deceased). Transition probabilities were obtained from observational studies and French national statistics, utilities from a previous US survey and costs from French national statistics. The analysis was conducted from societal and healthcare system perspectives. Mean time to nursing home admission was 4.57 years for ChEIs alone and 5.54 years for combination therapy, corresponding to 0.98 additional years, corresponding to a gain in quality adjusted life years (QALYs) of 0.25. From a healthcare system perspective, overall costs were €98,609 for ChEIs alone and €90,268 for combination therapy, representing cost savings of €8,341. From a societal perspective, overall costs were €122,039 and €118,721, respectively, representing cost savings of €3,318. Deterministic and probabilistic (Monte Carlo simulations) sensitivity analyses indicated that combination therapy would be the dominant strategy in most scenarios. In conclusion, combination therapy with memantine and a ChEI is a cost-saving alternative compared to ChEI alone as it is associated with lower cost and increased QALYs from both a societal and a healthcare perspective.     

Telehealth for patients with Parkinson’s disease: delivering efficient and sustainable long-term care

Objectives: We set out to demonstrate the benefits of providing long-term care via telehealth for patients with Parkinson’s disease living in continuous care facilities.

Methods: A cohort of 16 patients with Parkinson’s disease residing at one of 2 locations of a multi-facility continuous care retirement organization were seen virtually in follow-up over a 3-year period by Telehealth Services at a large, academic, tertiary care hospital in southeastern Pennsylvania. The data collected during that period, studied retrospectively, included demographic information, number of telehealth visits, and UPDRS scores obtained at each visit. Satisfaction and potential cost savings were also reviewed.

Results: UPDRS scores declined over the period of observation, from a range of 18-60 at study start to 28-72 at study end. Actual cost savings are difficult to define; however, the cost per telehealth visit at $117.30 was often lower than the facility’s average cost for transporting patients to a visit in the neurologist’s office. Patients, families, subspecialists, and the nursing staff expressed uniformly high satisfaction with telehealth.

Conclusion: This model for providing care proved to be sustainable and efficient, and promoted collaboration among the providers at the long-term care facility and those at the remote site. These benefits may be applicable to patients with degenerative disorders in similar settings.     

Neuroticism and extraversion in association with quality of life in patients with Parkinson’s disease

Purpose  Personality traits appear as determinants of quality of life (QoL) in most chronic diseases. The aim of this study is to explore whether neuroticism and extraversion contribute to the variance in QoL in patients with Parkinson’s disease (PD) when controlled for age, functional status and disease duration. Methods  The Parkinson’s Disease Quality of Life Questionnaire (PDQ-39) was used to assess QoL and the Unified Parkinson’s Disease Rating Scale (UPDRS) for disease severity. Neuroticism and extraversion were measured with the Eysenck Personality Questionnaire (EPQR-A). Multiple linear regression analysis was then used to assess the contribution of neuroticism and extraversion to QoL. Results  The sample consisted of 153 PD patients (48.4% women; 67.9 ± 9.3 years; mean disease duration 7.5 ± 5.8 years). Neuroticism was, after disease severity, the second most important variable associated with QoL in PD patients, in particular for domains associated with psychological processes: emotional well-being, social support, stigma and communication. A higher score in extraversion was significantly associated with better emotional well-being in males, but surprisingly, with worse emotional well-being in females. Conclusions  After functional status, personality traits were clearly associated with QoL in PD patients. Therefore, they should be taken into account by health-care professionals in their appraisal of patient complaints.     

Quality of life in Serbian patients with Parkinson’s disease

Background  The Parkinson’s Disease Questionnaire (PDQ-39) is a well-validated British scale for the assessment of health-related quality of life (QoL) in Parkinson’s disease (PD). Objective  To validate the Serbian version of the PDQ-39, while also providing additional information on the characteristics of this instrument. Patient and methods  A total of 102 Serbian PD patients were asked to complete the PDQ-39, a disease-specific QoL questionnaire, as well as the generic, health status questionnaire (SF-36-version 1), and the 21-item Beck Depression Inventory. Neurological examination included the Hoehn and Yahr staging, Unified Parkinson’s disease rating scale (UPDRS)-part III, Schwab and England scale, and the Mini-Mental State Examination. Results  Internal consistency analysis yielded a Cronbach’s α of 0.83. Cronbach’s α was above 0.70 for seven out of eight subscales (range from 0.73 to 0.91). A hierarchical structure of the PDQ-39 was revealed, with one global higher-order factor and two lower-order factors. The strongest predictor of the QoL in PD was the presence of depression, while motor disability (UPDRS-part III score) additionally contributed to poor QoL. Cognitive impairment has not been correlated with poor QoL. Also, QoL measures were not different between young- (≤50 years) and older-onset PD patients. Conclusions  The PDQ-39 is a reliable and valid instrument for the assessment of QoL in Serbian PD patients.     

Diagnosis of Alzheimer’s disease patients with rapid cognitive decline in clinical practice: Interest of the Deco questionnaire

Background  

Patients with Alzheimer’s disease (AD) who deteriorate rapidly are likely to have a poorer prognosis. There is a clear need for a clinical assessment fool to defect, such a decline in newly diagnosed patients.     

Potential cost-effectiveness of a family-based program in mild Alzheimer’s disease patients

Alzheimer’s disease (AD) is a chronic and progressive neurodegenerative disease characterized by a progressive deterioration in cognitive functions. AD will have a major impact on public health in the coming decades. The objective of this study was to evaluate the potential cost-effectiveness of a cognitive-behavioral family intervention (CBFI) program in patients with mild Alzheimer’s disease in Finland. A second-order Monte Carlo technique was used to simulate the effectiveness of the intervention in AD patients and their informal caregivers over the course of 5 years. A Bayesian approach was applied to answer the question: how likely is it that the CBFI program is cost-effective? Based on existing information, the incremental net health benefit of the CBFI program is positive with over 0.9 probability, which indicates that the CBFI program has the highest probability of being optimal by providing greater net benefits than current practice. Furthermore, changes in the health-related quality of life of the caregivers were insensitive to AD patients’ disease stage and settings of care. From the methodological point of view, the acceptability curve with a Bayesian approach provides a flexible way to characterize uncertainty surrounding cost-effectiveness parameters.     

The independent role of inflammation in physical frailty among older adults with mild cognitive impairment and mild-to-moderate Alzheimer’s disease

Objectives

To examine the independent and combined effects of inflammation and endocrine dysregulation on (i) baseline frailty status and (ii) frailty progression at one year, among cognitively impaired community dwelling older adults.

Design

Prospective cohort study.

Setting

Tertiary Memory Clinic.

Methods

We recruited patients with mild cognitive impairment and mild-moderate Alzheimer’s disease. Physical frailty status was assessed at baseline and 1-year. Blood biomarkers of systemic inflammation [interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α)] and anabolic hormones [insulin-like growth factor-1 (IGF-1), dehydroepiandrosterone sulphate (DHEAS)] were measured at baseline and examined in relation to physical frailty status at baseline and progression at 1-year. Each subject was categorized as (i) neither pro-inflammatory nor endocrine deficient, (ii) pro-inflammatory (IL-6 or TNF-α, or both, being in highest quartile) but not endocrine deficient, (iii) endocrine deficient (IGF-1 or DHEAS, or both, being in lowest quartile) but not pro-inflammatory and (iv) both pro-inflammatory and endocrine deficient.

Results

Twenty (20.2%) of 99 subjects were physically frail at baseline. There was no association between severity of cognitive impairment and baseline frailty status, but the frail group had significantly greater hippocampal atrophy (median MTA: 2 (2–3) vs 1 (1–2), p=0.010). TNF-α was significantly higher in subjects who were physically frail at baseline (median TNF-α: 1.30 (0.60–1.40) vs 0.60 (0.50–1.30) pg/mL, p=0.035). In multiple logistic regression adjusted for age and gender, a pro-inflammatory state in the absence of concomitant endocrine deficiency was significantly associated with physical frailty at baseline (OR=4.99, 95% C.I 1.25–19.88, p=0.023); this was no longer significant when MTA score was included in the model. Isolated pro-inflammatory state (without endocrine deficiency) significantly increased the odds of frailty progression (OR=4.06, 95% CI 1.09–15.10, p=0.037) at 1-year. The combination pro-inflammatory and endocrine deficient state was not significantly associated with either baseline or progressive physical frailty.

Conclusion

A pro-inflammatory state exerts differential effects on physical frailty, contributing to the increased risk of baseline and progressive frailty only in the absence of a concomitant endocrine deficient state, with potential mediation via neurodegeneration.

     

Relative contributions of biomarkers in Alzheimer’s disease

PurposeTo assess relationships between biomarkers for Alzheimer’s disease (AD) and their potential contributions to AD.MethodsBiomarkers and cognitive evaluations were assessed longitudinally in 179 patients with mild cognitive impairment, from the Alzheimer’s Disease Neuroimaging Initiative from 2003 to 2006, and were used to examine, at any given time, the joint contributions of hippocampal volume, whole brain volume, and brain glucose metabolism on clinical AD progression, using the Alzheimer’s Disease Assessment Scale-Cognitive subscale (ADAS-Cog). Marginal structural models were applied, and an inverse-probability of treatment weight estimation was used to account for time-dependent confounding between study variables.ResultsAt any given time, population-level differences (e.g., 1-standard deviation [SD] increase) in brain glucose metabolism (?1.036; 95% confidence interval [95% CI], ?1.608, ?0.464) and hippocampal volume (–1.537; 95% CI, ?2.399, ?0.674) independently reduced mean (ADAS-Cog), whereas a 1-SD increase in whole brain volume did not (0.372; 95% CI, ?0.283, 1.027). The effects of brain glucose metabolism differed in subgroups defined by baseline covariates (e.g., age), but no subgroup effects were observed for hippocampal volume and brain volume.ConclusionsBrain glucose metabolism and hippocampal volume represent relevant biological markers in subjects at risk for AD.