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Biomedical subjects

Kenneth Rockwood

Publications and source records attributed to Kenneth Rockwood.

At least 19 recordsLinked to original sources
PubMed2007

Specific symptomatic changes following donepezil treatment of Alzheimer's disease: a multi-centre, primary care, open-label study.

BACKGROUND: Standard measurement scales used in anti-dementia trials may not capture symptomatic changes recognized by clinicians and caregivers. We studied a symptom checklist, completed separately by caregivers and by clinicians, to identify patterns of change associated with donepezil treatment. METHODS: In a multi-centre, 6-month, open-label study of 101 primary care patients, changes in a 19-symptom checklist were assessed in relation to changes in standardized scales of cognition, activities of daily living, behavior, and caregiver burden. RESULTS: Three symptoms were reported in more than 80% of patients by both clinicians and caregivers: problems in remembering, (97%), temporal orientation (89%), and repetitiveness (85%). Five others overlapped on each of the clinician and caregiver 'top ten', including cognitive activation, spatial orientation, leisure, attention, and apathy. Clinicians reported that symptoms did not improve in 38 patients, whereas there was some improvement in 43, and improvement in most symptoms in 20. Caregivers reported that symptoms did not improve in 55 patients, whereas 27 and 19 patients showed some and most symptoms improving respectively. Patients with the greatest symptomatic improvement also improved most on the ADAS-Cog and the other standardized measures, whereas no improvement (or decline) in each standardized measure was observed in people whose symptoms worsened or did not improve. CONCLUSION: A symptom checklist allowed clinically meaningful profiles to be identified, but revealed different estimates of response between clinicians and caregivers. Both agreed that improved executive function was the most common response. A symptom checklist can help translate between standard measures and everyday practice.

Activities of Daily Living↗
PubMed2006

Disease progression in vascular cognitive impairment: cognitive, functional and behavioural outcomes in the Consortium to Investigate Vascular Impairment of Cognition (CIVIC) cohort study.

BACKGROUND AND PURPOSE: Empirical studies to clarify the outcomes in Vascular Cognitive Impairment (VCI) are needed. We compared cognitive, functional, and behavioural outcomes in patients with VCI to patients with no cognitive impairment (NCI), and Alzheimer's disease (AD). METHODS: Secondary analysis of the Consortium to Investigate Vascular Impairment of Cognition (CIVIC), a multi-centre Canadian memory clinic 30-month cohort study. RESULTS: Of 1347 patients, 938 were eligible for follow-up, of whom 239 (24.5%) were lost and 29 (3%) had died. Of the remaining 697 patients, 125 had NCI, 229 had VCI, and 343 had AD at baseline. Compared to people with NCI, of whom 20-40% showed progression based on cognitive and functional measures, those with VCI were more likely to progress (50-65%), as were people with AD (50-80%) (p<0.01). More people with VCI showed progression of affective symptoms (30%) than those with NCI (12%) or AD (15% p<0.01). Progression of impaired judgment (rated clinically) in VCI (15%) was similar to AD (11%) but more common than in NCI (4%, p<0.01). CONCLUSIONS: Most people with VCI show readily detectable progression by 30 months. Depressive symptoms were more common and more progressive in VCI than in Alzheimer's disease, whereas clinical evidence of progressive executive dysfunction was common in both AD and VCI.

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PubMed2006

A cross-national study of transitions in deficit counts in two birth cohorts: implications for modeling ageing.

Generally, health does not improve with age, and many physical and physiological functions are known to decline. These changes do not occur uniformly, however; for many reasons, some people experience significant improvement in their health over non-trivial time intervals. Earlier, we showed that 5-year transitions in health status in elderly people (age 65+ years) can be modeled as a stochastic process, using a modified Poisson distribution with four readily interpretable parameters. The original description was based on follow-up of a single cross-sectional study, thus mixing age and cohort effects. Here, we again used a multistate Markov chain to model 5-year deficit accumulation in relation to frailty in both a Swedish birth cohort (aged 70 years at inception) and, from the original cross-sectional study, a Canadian birth cohort, aged 69-71. In both datasets, we found again that a modified Poisson describes the transition in health status with high precision. The parameters of the model though different, are close to each other, even though the cohorts are from different countries, were assembled 20 years apart, and counted different deficits. The model suggests that all health transitions, including health improvement, worsening, and death, can be summarized in a unified stochastic model with a few interpretable parameters.

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PubMed2006

Outcomes of cognitively impaired not demented at 2 years in the Canadian Cohort Study of Cognitive Impairment and Related Dementias.

BACKGROUND: People who are cognitively impaired not demented (CIND) can be at an increased risk for developing dementia, but little is known about the natural history of CIND in clinical settings. METHOD: We examined the 2-year outcome of CIND subjects in the Canadian Cohort Study of Cognitive Impairment and Related Dementias.CIND was diagnosed when at least one positive item was endorsed on the DSM-III-R dementia criteria, but not all criteria were met. CIND was further subclassified as: pre-Alzheimer's disease (pre-AD), vascular cognitive impairment (VCI-ND), non-AD degenerative, psychiatric, other neurologic, other medical conditions, mixed disorders and no etiology identified (not otherwise specified [NOS]). RESULT: Of 146 CIND patients with 2-year follow-up data available, 49 (34%) progressed to dementia, while 20 (14%) recovered to not cognitively impaired (NCI). Progressors were significantly older than stable CIND and reverters (p < 0.0001; mean age = 71.1, 64.3, and 59.1, respectively), and there were significantly (p = 0.001) more ApoE epsilon4 carriers among progressors (67%) than stable CIND (29%) and reverters (12%). Pre-AD CIND and VCI-ND had the highest rate of conversion to dementia (41.0 and 40.0%, respectively), while psychiatric CIND and CIND NOS had highest rate of recovery to NCI (20.0 and 30.0%, respectively). All conversions in pre-AD CIND were to 'probable AD'. CONCLUSION: CIND consists of a heterogeneous group of disorders that can be classified syndromically. Many subclassess - not just those with pre-AD CIND - are at high risk of progression to dementia, usually to Alzheimer's disease.

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PubMed2006

Prevalence and outcomes of delirium in community and non-acute care settings in people without dementia: a report from the Canadian Study of Health and Aging.

BACKGROUND: While delirium is common among older adults in acute care hospitals, its prevalence in other settings has been less well studied. We examined delirium prevalence and outcomes in a large cohort of older Canadians living outside of acute care. METHODS: In this secondary analysis of the Canadian Study of Health and Aging, the prevalence of clinically diagnosed delirium was estimated and five-year survival was compared with that of individuals with dementia of graded severity. RESULTS: Delirium was very uncommon (prevalence <0.5%) and was associated with reduced survival, similar to that of moderate-to-severe dementia. CONCLUSION: In this cohort of older Canadians, delirium in non-demented people was associated with very low 5-year survival, at levels comparable with advanced dementia. Although it is common in hospital, delirium is uncommon among older adults in their usual place of residence, suggesting that it is a potent stimulus to seek medical care.

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PubMed2006

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 Alzheimer's 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 Alzheimer's 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 Alzheimer's Disease Assessment Scale (ADAS-cog), the Clinician's 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 Alzheimer's disease who were taking galantamine than among those who were taking placebo.

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PubMed2006

Going from bad to worse: a stochastic model of transitions in deficit accumulation, in relation to mortality.

As people age, they accumulate deficits. The more deficits they accumulate, the greater their vulnerability, which can be expressed as the probability to accumulate even more deficits, or to die. The probability of death is known to be exponentially related to the number of deficits. Using data from elderly (aged 65 + years) participants in the Canadian Study of Health and Aging (n = 9008), we investigated the relationship between the number of deficits and the change in the number of deficits over two successive 5 year intervals. We show that the probabilities of changes in the number of deficits, in relation to baseline, are well fitted (R(2) > 0.98) by a simple distribution, with two parameters. The model suggests a maximum to deficit accumulation, and illustrates no level of deficit accumulation at which there is a net gain in fitness. Age-related deficit accumulation is highly characteristic, and can be modeled as a stochastic process with readily interpretable parameters.

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PubMed2006

Limits to deficit accumulation in elderly people.

We evaluated limits to the accumulation of deficits (symptoms, diseases, disabilities) for 33,069 people aged 65+ years. We combined deficits in a frailty index (theoretical range 0-1) and found that the 99% limit varied little between samples, representing a frailty index value of about 0.65 +/- 0.05. This near-maximum shows no relationship with age. It is the same in community and institutional samples, even though the mean value is much higher in the latter. The data suggest a level of frailty beyond which, even in developed countries, further deficit accumulation is not sustainable.

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PubMed2006

Verbal repetition in patients with Alzheimer's disease who receive donepezil.

BACKGROUND: Current outcome measures for Alzheimer's disease (AD) drugs have been criticized as insufficiently patient-centred. One commonly unmeasured goal of patients and caregivers is verbal repetition. OBJECTIVES: We examined how often reducing repetition (of questions, statements or stories) was set as treatment goal, whether and when it responded, and how change in repetition correlated with change in other domains. METHODS: This is a secondary analysis of the open-label Atlantic Canada Alzheimer's Disease Investigation of Expectations study of donepezil for mild-moderate AD in 100 community-dwelling people. Goal Attainment Scaling, an individualized account of the goals of treatment, was the primary outcome measure. RESULTS: Reducing repetition was a treatment goal in 46%, who were not systematically different from others. Of 18 patients in whom repetition improved for 9 months, 83% (15) showed a response at 3 months. Early (3-month) response correlated best with the overall level of goal attainment (r = 0.74) and changes in leisure activities (r = 0.69) and social interactions (r = 0.68) compared with changes in cognition (r = 0.44) or behaviour (r = 0.11). Correlations with the ADAS-Cog and MMSE change scores remained only modest (at 12 months = -0.25 and 0.19, respectively). Correlations with the CIBIC-Plus were higher (-0.47 at 3 months and -0.43 at 12 months). CONCLUSION: Diminution of repetition is common, and appears to mark response to cholinesterase inhibition in some patients. Responders generally also show improved cognition and function, perhaps as an aspect of improved executive function.

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PubMed2006

Cognitive impairment of acute onset in the Consortium to Investigate Vascular Impairment of Cognition (CIVIC) study: occurrence, correlates, and outcomes.

OBJECTIVE: Having demonstrated that dementia of acute onset represents a distinct syndrome with distinct outcomes, the authors investigated whether similar attributes describe cognitive impairment of acute onset (CIAO). METHODS: The authors conducted a secondary analysis of the Consortium to Investigate Vascular Impairment of Cognition study. RESULTS: Ninety patients met our criteria for CIAO. Compared with cognitive impairment of gradual onset, CIAO was associated with vascular features (odds ratio [OR]: 12.3, 95% confidence interval [CI]: 3.2-47.9), dementias other than Alzheimer disease (OR: 6.5, 95% CI: 2.1-20.8), and decreased survival (hazard ratio: 2.8, 95% CI: 1.6-4.6). CONCLUSIONS: Patients with CIAO are clinically identifiable and have distinct outcomes.

Acute Disease↗
PubMed2006

Long-term risks of death and institutionalization of elderly people in relation to deficit accumulation at age 70.

OBJECTIVES: To measure relative fitness and frailty in older people without specific frailty instruments and to relate that measurement to long-term health outcomes. DESIGN: Retrospective cohort studies. SETTING: Two population-based studies of people aged approximately 70 at baseline and followed up to 10 years (in the Canadian Study of Health and Aging (CSHA)) or 26 years in the Gothenburg H-70 cohort study. PARTICIPANTS: Nine hundred sixty-two men and 1,178 women. MEASUREMENTS: Deficit accumulation (the exposure) was counted using self-reported (CSHA) or clinically designated (H-70) symptoms, signs, diseases, and disabilities. Relative fitness and frailty were measured in relation to the degree of deficit accumulation evaluated in four quartiles, representing those most fit to those most frail. The items that made up the frailty index were selected randomly without replacement in 1,000 iterations. The outcomes were risks of death or residential long-term care. RESULTS: Worse frailty, however measured, was associated with worse survival; the Kaplan-Meier curves of random iterations of the frailty definition showed virtually no interquartile overlap for mortality. For any given level of frailty, men died younger than women. Worse frailty was also associated with a higher risk of institutionalization. CONCLUSION: Frailty appears to be a robust concept that is readily operationalized, with the risk of adverse outcomes being largely established by age 70.

Activities of Daily Living↗
PubMed2005

Nodding and napping in medical lectures: an instructive systematic review.

A comprehensive, international systematic review, spanning more than 100 years of data collection, suggests that soporific lectures at medical meetings are common, annoying and persistent. Low lights and boring material are prominent risk factors for nodding off during presentations. Extreme remedial measures are warranted.

Boredom↗
PubMed2005

Improved prediction of early-onset coronary artery disease using APOE epsilon4, BChE-K, PPARgamma2 Pro12 and ENOS T-786C in a polygenic model.

OBJECTIVES: Coronary artery disease (CAD) is often polygenic due to multiple mutations that contribute small effects to susceptibility. Since most prior studies only evaluated the contribution of single candidate genes, we therefore looked at a combination of genes in predicting early-onset CAD [apolipoprotein E (APOE) epsilon4, butyrylcholinesterase (BChE) K, peroxisome proliferator-activated receptor gamma2 (PPARgamma2) Pro12Ala and endothelial nitric oxide synthase (ENOS) T-786C]. DESIGN AND METHODS: We examined the frequencies, individually and in combination, of all four alleles among patients with early-onset CAD (n = 150; <50 years), late-onset CAD (n = 150; >65 years) and healthy controls (n = 150, age range 47-93 years). Differences in the proportion of subjects in each group with the given gene combination were assessed and likelihood ratios (LR) were calculated using logistic regression to combine the results of multiple genes. RESULTS: Early-onset CAD patients had increased, but non-significant, frequencies of PPARgamma2 Pro12/Pro12 (P = 0.39) and ENOS T-786C (P = 0.72), while BChE-K was only significantly higher in early-onset CAD patients compared to controls (P = 0.03). There were significantly more APOE epsilon4 alleles alone (P = 0.02) or in combination with BChE-K (P = 0.02) among early-onset CAD patients compared to late-onset CAD ones or controls. When combined, there was a higher prevalence of all four alleles in early-onset CAD (early-onset CAD patients: 10.7%, late-onset CAD patients: 3.3% and controls: 2.7%, P = 0.01). LR for early-onset CAD for a single allele was relatively small (1.08 for PPARgamma2 to 1.70 for APOE epsilon4). This increased to 2.78 (1.44-5.37) when combining all four alleles, therefore increasing the pre-test probability of CAD from 5% to a post-test probability of 12.7%. CONCLUSIONS: While any single mutation causes only a mildly increased LR (none > 1.7), in combination, the likelihood of early-onset CAD increased to 2.78 with four mutations. The genetics of early-onset CAD appear to be multifactorial, requiring polygenic models to elucidate risk.

Age of Onset↗
PubMed2005

Decrease in the relative heterogeneity of health with age: a cross-national comparison.

Using data from seven studies from Canada, Australia and the United States we were able to evaluate the heterogeneity of health status for 34,095 people aged 60 years and older. We found that relative heterogeneity (measured by the coefficient of variation) decreased with age. The coefficient of variation also decreased as a function of deficit accumulation (i.e. was lower when people demonstrated more deficits) displaying a power-law relationship. The exponent was close to 0.5, and therefore belongs to the dynamic universality class, which is typical for complex dynamical networks. We interpret this as showing that decline in relative heterogeneity is a robust finding, and represents, at the group level, increased vulnerability amongst elderly people.

Age Distribution↗
PubMed2005

Clinical and radiographic subtypes of vascular cognitive impairment in a clinic-based cohort study.

BACKGROUND AND PURPOSE: There is a need for empirical studies to define criteria for vascular cognitive impairment (VCI) subtypes. In this paper, we report the predictive validity of a subtype classification scheme based on clinical and radiographic features. METHODS: Nine Canadian memory clinics participated in the Consortium to Investigate Vascular Impairment of Cognition. This cohort consisted of 1347 patients, of whom 324 had VCI, and was followed for up to 30 months. RESULTS: Clinical and neuroimaging features defined three subtypes: vascular cognitive impairment, no dementia, (n=97), vascular dementia (n=101) and mixed neurodegenerative/vascular dementia (n=126). Any ischemic lesion on neuroimaging increased the odds (odds ratio=9.31; 95% confidence interval 6.46, 13.39) of a VCI diagnosis. No VCI subtype, however, was associated with a specific neuroimaging abnormality. Compared to those with no cognitive impairment, patients with each VCI subtype had higher rates of death and institutionalization (hazard ratio for combined adverse events=6.08, p<0.001). CONCLUSIONS: Both clinical features and radiographic features help establish a diagnosis of VCI. The outcomes of VCI subtypes, however, are more strongly associated with clinical features than with radiographic ones.

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