Chris MacKnight

A global clinical measure of fitness and frailty in elderly people

Background: There is no single generally accepted clinical definition of frailty. Previously developed tools to assess frailty that have been shown to be predictive of death or need for entry into an institutional facility have not gained acceptance among practising clinicians. We aimed to develop a tool that would be both predictive and easy to use. Methods: We developed the 7-point Clinical Frailty Scale and applied it and other established tools that measure frailty to 2305 elderly patients who participated in the second stage of the Canadian Study of Health and Aging (CSHA). We followed this cohort prospectively; after 5 years, we determined the ability of the Clinical Frailty Scale to predict death or need for institutional care, and correlated the results with those obtained from other established tools. Results: The CSHA Clinical Frailty Scale was highly correlated (r = 0.80) with the Frailty Index. Each 1-category increment of our scale significantly increased the medium-term risks of death (21.2% within about 70 mo, 95% confidence interval [CI] 12.5%–30.6%) and entry into an institution (23.9%, 95% CI 8.8%–41.2%) in multivariable models that adjusted for age, sex and education. Analyses of receiver operating characteristic curves showed that our Clinical Frailty Scale performed better than measures of cognition, function or comorbidity in assessing risk for death (area under the curve 0.77 for 18-month and 0.70 for 70-month mortality). Interpretation: Frailty is a valid and clinically important construct that is recognizable by physicians. Clinical judgments about frailty can yield useful predictive information.

Diabetes mellitus and the Risk of Dementia, Alzheimer’s Disease and Vascular Cognitive Impairment in the Canadian Study of Health and Aging

Background: Conflicting results have been reported about the status of diabetes mellitus as a risk for Alzheimer’s disease. We investigated the relationship between diabetes and incident dementia (including Alzheimer’s disease and vascular cognitive impairment) in a 5-year longitudinal study. Methods: Secondary analysis of the Canadian Study of Health and Aging, a representative cohort study of dementia in older Canadians. Results: 5,574 subjects without cognitive impairment at baseline participated in 5-year follow-up. Diabetes mellitus at baseline was associated with incident vascular cognitive impairment (RR: 1.62; 95% CI: 1.12–2.33) and its subtypes, vascular dementia (RR: 2.03; 95% CI: 1.15–3.57), and vascular cognitive impairment not dementia (RR: 1.68; 95% CI: 1.01–2.78). Diabetes was not associated with mixed Alzheimer’s/vascular dementia (RR: 0.87; 95% CI: 0.34–2.21), incident Alzheimer’s disease (RR: 1.30; 95% CI: 0.83–2.03) or all dementias (RR: 1.26; 95% CI: 0.90–1.76). Conclusions: Despite increased recognition of the role of vascular factors in Alzheimer’s disease, we did not find an association between diabetes and incident Alzheimer’s disease, even though diabetes was associated with incident vascular cognitive impairment.

Donepezil for Treatment of Dementia With Lewy Bodies: A Case Series of Nine Patients

Dementia with Lewy bodies (DLB) is common. Symptomatic treatment can be difficult. We reviewed nine consecutive patients with DLB (mean age 77.5 [range 67 to 84] years; seven men and two women; mean duration of disease 3.7 [range 1.5 to 8.0] years) who had been treated with donepezil. Each initially received 2.5 to 5 mg per day of donepezil, and was stabilized on 5 mg per day. Donepezil was increased to 10 mg per day in five patients. The mean observation period was 12 (range 8 to 24) weeks. Target symptoms included cognition, hallucinations, parkinsonism, and functional abilities. By both cognitive testing and family reports, cognition improved in seven of nine patients, remained the same in one of nine, and fluctuated in one of nine (mean Mini-Mental State Examination change 4.4 +/- 6.3 points). Function was improved or maintained in six of nine patients and fluctuated in two of nine. Hallucinations initially worsened, then fluctuated in one patient, but improvement in frequency, duration, and content was reported in eight of nine cases. In three of nine patients, treatment with donepezil resulted in worsening of parkinsonism, which in each case responded to levodopa/carbidopa. Treatment of DLB patients with donepezil for 12 weeks most commonly improved hallucinations, and sometimes improved cognition and overall function. Treatment with donepezil was sometimes associated with worse parkinsonism.

Conceptualisation and Measurement of Frailty in Elderly People

The use of the term ‘frailty’ has shown tremendous growth in the last 15 years, but this has not been accompanied by a widely accepted definition, let alone agreed-upon measures. In this paper, we review approaches to the definition and measurement of frailty and discuss the relationship between frailty, aging and disability. Two trends are evident in definitions, which often trade off comprehensiveness for precision: frailty can be seen as being synonymous with a single-system problem or as a multisystem problem. The essential feature of frailty is the notion of risk due to instability (itself suggesting a balance of many factors), and has been only poorly measured to date. Future models of frailty should incorporate more precise operationalisation of the probability of frailty and better explain the relationship between disease, disability and frailty.

The mortality rate as a function of accumulated deficits in a frailty index.

In a representative Canadian population survey (n=66589) the proportion of accumulated deficits in a frailty index showed a linear relationship with mortality in a log-log plot, such that the mortality rate was a power-law function of the frailty index. Represented in this way, the frailty index readily summarizes individual differences in health status. The exponent and amplitude parameters of the power function are gender specific, reflecting that while, on average, women accumulate more deficits than men of the same age, their risk of mortality is lower. The dependence of the mortality rate on the frailty index points to the merit of the index as a simple and accessible tool for estimating individual risks of mortality.

Attainment of treatment goals by people with Alzheimer's disease receiving galantamine: a randomized controlled trial

Background: Although cholinesterase inhibitors have produced statistically significant treatment effects, their clinical meaningfulness in Alzheimers disease is disputed. An important aspect of clinical meaningfulness is the extent to which an intervention meets the goals of treatment. Methods: In this randomized controlled trial, patients with mild to moderate Alzheimers disease were treated with either galantamine or placebo for 4 months, followed by a 4-month open-label extension during which all patients received galantamine. The primary outcome measures were Goal Attainment Scaling (GAS) scores from assessments by clinicians and by patients or caregivers of treatment goals set before treatment and evaluated every 2 months. Secondary outcome measures included the cognitive subscale of the Alzheimers Disease Assessment Scale (ADAS-cog), the Clinicians Interview-based Impression of Change plus Caregiver Input (CIBIC-plus), the Disability Assessment for Dementia (DAD) and the Caregiving Burden Scale (CBS). To evaluate treatment effect, we calculated effect sizes (as standardized response means [SRMs]) and p values. Results: Of 159 patients screened, 130 (mean age 77 [standard deviation (SD) 7.7]; 63% women) were enrolled in the study (64 in the galantamine group and 66 in the placebo group); 128 were included in the analysis because they had at least one post-baseline evaluation. In the intention-to-treat analysis, the clinician-rated GAS scores showed a significantly greater improvement in goal attainment among patients in the galantamine group than among those in the placebo group (change from baseline score 4.8 [SD 9.6]) v. 0.9 [SD 9.5] respectively; SRM = 0.41, p = 0.02). The patient– caregiver-rated GAS scores showed a similar improvement in the galantamine group (change from baseline score 4.2 [SD 10.6]); however, because of the improvement also seen in the placebo group (2.3 [SD 9.0]), the difference between groups was not statistically significant (SRM = 0.20, p = 0.27). Of the secondary outcome measures, the ADAS-cog scores differed significantly between groups (SRM = –0.36, p = 0.04), as did the CIBIC-plus scores (SRM = –0.40, p = 0.03); no significant differences were in either the DAD scores (SRM = 0.28, p = 0.13) or the CBS scores (SRM = –0.17, p = 0.38). Interpretation: Clinicians, but not patients and caregivers, observed a significantly greater improvement in goal attainment among patients with mild to moderate Alzheimers disease who were taking galantamine than among those who were taking placebo.

Some mathematical models of frailty and their clinical implications

Frailty is a term that is used often, but commonly not defined precisely. As reviewed elsewhere most definitions share several features. Typically, older adults who are frail have a greater rate of dependence on others, so-called ‘loss of physiological reserve’ and multiple diseases. A dynamic component is often included (e.g. ‘loss of reserve’ and such synonyms as ‘unstable disability’ and ‘impaired homeostenosis’) and is manifest when, over time, patients respond less well to stress, or when those with given levels of frailty have higher rates of adverse outcomes. Still, the imprecision of the term frailty has led some to question its merit, and either to develop alternative means of classification or to stay with the concept of function and disability. Alternative methods of classification are either broadly or narrowly focussed.

Spectrum of Disease in Vascular Cognitive Impairment

The recognition that cognitive impairment of vascular origin is not limited to multi-infarct dementia has led to the development of several sets of new criteria for vascular dementia (VaD). We set out to define the spectrum of disease in patients presenting with vascular cognitive impairment (VCI). Of 412 patients consecutively seen at a memory clinic, 80 had VCI. These patients had vascular cognitive impairment not dementia (n = 19), VaD (n = 48), and mixed Alzheimer’s disease-VaD (n = 13). Radiographic patterns were: white matter changes only (40%); multiple infarcts (30%); single strategic stroke (14%), and no identified lesion (16%). Of note, 19 (24%) of these patients meet none of the currently published criteria for VaD. To better understand and treat ischaemic causes of cognitive impairment, the concept of VaD should be expanded to include patients who do not meet traditional dementia criteria.

The Accumulation of Deficits with Age and Possible Invariants of Aging

This paper extends a method of apprising health status to a broad range of ages from adolescence to old age. The “frailty index” is based on the accumulation of deficits (symptoms, signs, disease classifications) as analyzed in the National Population Health Survey, a representative Canadian population sample (n = 81,859). The accumulation of deficits has both an age-independent (background) component and an age-dependent (exponential) component, akin to the well-known Gompertz-Makeham model for the risk of mortality. While women accumulate more deficits than men of the same age, on average, their rate of accumulation is lower, so the difference in the level of deficits between men and women decreases with age. Two possible invariants of the process of accumulation of deficits were found: (1) the age at which the average proportion of deficits coincides for men and women is 94 years, which closely matches the species-specific lifespan in humans (95 ± 2); (2) the value of the frailty index (proportion of deficits), which corresponds to that age (0.18). The similarity between mortality kinetics and the accumulation of deficits (frailty kinetics), and the coincidence of the time parameters in the frailty and mortality models make it possible to express mortality risk in terms of accumulated deficits. This provides a simple and accessible tool that might have potential in a number of biomedical applications.

ASSESSMENT OF INDIVIDUAL RISK OF DEATH USING SELF-REPORT DATA: AN ARTIFICIAL NEURAL NETWORK COMPARED WITH A FRAILTY INDEX

Objectives: To evaluate the potential of an artificial neural network (ANN) in predicting survival in elderly Canadians, using self‐report data.