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Kenneth Rockwood

Publications and source records attributed to Kenneth Rockwood.

At least 73 records · Page 4Linked to original sources
PubMed2003

Vascular cognitive impairment.

Cerebrovascular disease is the second most common cause of acquired cognitive impairment and dementia and contributes to cognitive decline in the neurodegenerative dementias. The current narrow definitions of vascular dementia should be broadened to recognise the important part cerebrovascular disease plays in several cognitive disorders, including the hereditary vascular dementias, multi-infarct dementia, post-stroke dementia, subcortical ischaemic vascular disease and dementia, mild cognitive impairment, and degenerative dementias (including Alzheimer's disease, frontotemporal dementia, and dementia with Lewy bodies). Here we review the current state of scientific knowledge on the subject of vascular brain burden. Important non-cognitive features include depression, apathy, and psychosis. We propose use of the term vascular cognitive impairment, which is characterised by a specific cognitive profile involving preserved memory with impairments in attentional and executive functioning. Diagnostic criteria have been proposed for some subtypes of vascular cognitive impairment, and there is a pressing need to validate and further refine these. Clinical trials in vascular cognitive impairment are in their infancy but support the value of therapeutic interventions for symptomatic treatment.

Cerebrovascular Disorders↗
PubMed2003

The treatment of Alzheimer's disease: success short of cure.

Metaphor has an important role in the discussion of scientific discovery because it enables researchers to talk about things of which their understanding is incomplete. Alzheimer's disease (AD) can be seen as a journey down a path, which becomes steadily less pleasant and ends in a wholly undesirable destination. To further the metaphor, treatments can be seen as attempts to help the patient return to the starting point, to slow the journey, or to stop at some point on the path. However, treatment may be successful but may not return the patient to their starting point or slow disease progression. We argue that treatments that steer the patient down a different path, to a destination preferable to that at the end of the AD path, can also be seen as successful. This metaphor has practical implications for clinical trials. It highlights the importance of individualised outcome measures that incorporate patients' preferences and should encourage us to develop better means of enabling the recovery of self. To understand how there can be treatment success short of cure, without knowing at the outset what form that success may take, will require systematic observation and careful description of patients' experiences.

Alzheimer Disease↗
PubMed2003

The Consortium to Investigate Vascular Impairment of Cognition: methods and first findings.

BACKGROUND: The Consortium to Investigate Vascular Impairment of Cognition (CIVIC) is a Canadian, multi-centre, clinic-based prospective cohort study of patients with Vascular Cognitive Impairment (VCI). We report its organization and the impact of diagnostic criteria on the study of VCI. METHODS: Nine memory disability clinics enrolled patients and recorded their usual investigations and care. A case report form included all vascular dementia (VaD) individual criteria for each of four sets (National Institute of Neurological Disorders and Stroke (NINDS-AIREN), Alzheimer's Disease Diagnostic Treatment Centers (ADDTC), the ICD-10 Classification of Mental and Behavioural Disorders (ICD-10), and the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV)) of consensus-based diagnostic criteria and for the Hachinski Ischemia Score (HIS). Investigators, having completed the case report form, were asked to make a clinical judgement about the cognitive diagnosis based on the best available information, including neuroimaging. RESULTS: Of 1,347 patients (mean age 72 years; 56% women), 846 (63%) were diagnosed with dementia and 324 (24%) were diagnosed with VCI. The proportion of patients diagnosed with VaD by the diagnostic criteria was: 23.9% (n = 322) by DSM-IV, 10.2% (n = 137) by HIS, 4.3% (n = 58) by ICD-10, 3.8% (n = 51) by ADTCC, and 3.6% (n = 48) by NINDS-AIREN. Judged against a clinical diagnosis of VaD, the sensitivity/specificity of each was: DSM-IV (0.77/0.80); HIS (0.41/0.92); ICD-10 (0.29/0.98); ADTCC (0.24/0.98); NINDS-AIREN (0.42/0.995). Compared with a clinical diagnosis of VCI, sensitivities were lower for the diagnostic criteria, reflecting the exclusion of patients who did not have dementia. CONCLUSIONS: Consensus-based criteria for VaD omit patients who do not meet dementia criteria that are modeled on Alzheimer's disease. Even for patients who do, the proportion identified with VaD varies widely. Criteria based on empirical analyses need to be developed and validated.

Adult↗
PubMed2003

Mixed dementia: Alzheimer's and cerebrovascular disease.

"Mixed dementia" is traditionally defined as Alzheimer's disease with cerebrovascular disease (CVD). Because the risks of both neurodegenerative dementias and cerebrovascular disease increase with age, the mixed dementias are likely the most common. In practice, patients with mixed dementia are diagnosed by one of two routes: Either they have evidence of a neurodegenerative dementia and CVD at the outset, or, they have a classical neurodegenerative presentation but are found to have ischemic lesions by neuroimaging. These facts have implications for the development of evidence-based diagnostic criteria.

Aged↗
PubMed2003

Does vascular MCI progress at a different rate than does amnestic MCI?

This article reviews the evidence available from natural history studies and randomized clinical trials (RCT) concerning what is now coined as amnestic MCI and vascular MCI and will answer the question about the similarity and difference of their progression toward dementia. The issues to be resolved prior to the use of a survival design for conversion from vascular MCI to dementia will be discussed.

Aged↗
PubMed2003

Vascular dementia.

Vascular dementia (VaD) is a term used to describe a particular constellation of cognitive and functional impairment, and is now generally seen as a subset of the larger syndrome of vascular cognitive impairment (VCI). The latter is seen as cognitive impairment in the face of cerebrovascular disease. VCI can be classified clinically by whether patients meet criteria for dementia, and whether the syndrome is distinct or overlaps with primary neurodegenerative diseases, such as Alzheimer's disease. This clinical classification can be further classified by neuroimaging, with subgroups that show cortical infarction, subcortical infarction and white matter changes, each alone or in combination. Understood in this way, VCI is likely the most common form of cognitive impairment in the population. Attempts to treat VaD had varying degrees of success, but it now appears that many forms of VCI might be preventable, especially with good control of vascular risk factors in middle age.

Aged↗
PubMed2003

APOE genotype, memory test performance, and the risk of Alzheimer's disease in the Canadian Study of Health and Aging.

OBJECTIVES: This study examined the relation between two risks for Alzheimer's disease (AD): the apolipoprotein (APOE) epsilon4 allele and poor memory test performance. METHODS: In the Canadian Study of Health and Aging (CSHA), a 5-year longitudinal population-based study that screened and followed over 10,000 participants, 2,914 had an initial clinical assessment and 1,624 had APOE genotype testing. All participants were categorized as having no cognitive impairment, cognitive impairment but no dementia, or dementia at both baseline and follow-up. We examined those (n = 209) with a complete neuropsychological assessment at baseline and no evidence of cognitive impairment who had either APOE epsilon3/epsilon3 or epsilon3/epsilon4 genotypes and who had a clinical consensus diagnosis of either no cognitive impairment or AD at follow-up. Delayed free recall memory was evaluated at CSHA-1 with the Buschke Cued Recall Test (BCRT). RESULTS: The risk of AD at follow-up was increased for participants with an APOE epsilon3/epsilon4 genotype when memory test performance was not considered, but logistic regression demonstrated that a model which also considered baseline memory test performance was more predictive of AD. In the more complete model, reduced BCRT free recall scores were associated with an increased risk of AD, whereas the risk associated with the APOE epsilon3/epsilon4 genotype was no longer significant. CONCLUSIONS: For those with no evidence of cognitive impairment, drawn from a population-based sample of elderly persons, the APOE epsilon3/epsilon4 genotype was only associated with an increased risk of AD after 5 years if their memory test performance was relatively poor at baseline. Regardless of the APOE genotype, and in the absence of clinical evidence of cognitive impairment, reduced scores on a test of delayed free recall at baseline was associated with an increased risk of AD after 5 years.

Aged↗
PubMed2003

Patterns of clinically detectable treatment effects with galantamine: a qualitative analysis.

The Clinician's Interview Based Impression of Change, plus carer interview (CIBIC-Plus) is widely used in anti-dementia drug trials. It includes clinicians' notes about patients' behaviour, function, and cognition, and a 7-point clinical global impression of change scale that summarizes patients' changes during treatment. We analyzed the narrative content of clinicians' notes from a randomized, controlled trial of galantamine, an anti-Alzheimer's disease drug, and identified varying degrees of improvement and decline. In general, while most patients were rated as showing 'no change', considerable changes were seen in such patients, but were judged by clinicians to have been offset by decline in other areas. Most patients rated as 'improved' showed combinations of cognitive, functional and/or behavioural improvement or stability. While patients with signs of cognitive improvement could be found across the scale from 'very much improved' to 'minimally worse', patients with functional improvement were rated as having improved or not having changed. Cognitive declines in several domains or any cognitive decline seen with functional declines were the chief drivers of worsening ratings. The CIBIC-Plus notes have potential value in identifying reproducible patterns of clinically relevant treatment effects provided that data are consistent and specific, and that seemingly contradictory information is carefully explored. Clinicians appear to be skeptical of cognitive changes not supported by like changes in function or behaviour.

Aged↗
PubMed2003

The risk of dementia in relation to statins and other lipid lowering agents.

Recent epidemiological reports suggest that statins, and possibly other lipid lowering agents, might be protective for Alzheimer disease, and for other types of dementia. Importantly, however, epidemiological reports of this type are susceptible to indication bias, i.e. people who elect to take lipid-lowering agents might be healthier than those who do not, so that it may be these other health factors which explain their lower risk of dementia. Limited clinical trials data support the notion that statins, in particular, have important effects on cerebral cholesterol metabolism, but the link to clinical effects in dementia has yet to be established, and the mechanisms by which lipid lowering agents might confer protective effects is unclear. Dedicated clinical trials are now under way, and their results are awaited with great interest.

Alzheimer Disease↗
PubMed2002

Vascular cognitive impairment and vascular dementia.

The criteria for vascular dementia (VaD) depend on first diagnosing dementia using Alzheimer-type criteria, upon which are superimposed vascular events, usually following a stroke model. This if often inappropriate, however, as memory loss is not always prominent in VaD. Alzheimer-type criteria will not detect these patients, and much brain injury can occur without resulting in classical features of stroke. VaD is often only diagnosed when dementia is clinically manifest, already too late to influence the early progression of the disease. Moreover, the predominating consensus-based criteria have demonstrably poor reliability. These shortcomings in the diagnosis of VaD have led to the development of the concept of vascular cognitive impairment (VCI), a broader term that is intended to detect cognitive loss before the dementia advances beyond effective treatment. Criteria for VCI are in the early stages of development. A lack of data on the beginnings of cognitive loss has inhibited their formalization, but it appears that the level of cognition should be set at a sensitive rather than a specific level. Similarly, for routine purposes, neuroimaging evidence of any cerebrovascular disease may be sufficient to document VCI and specific localization is not required. The current clinical criteria for VaD are probably not applicable for the diagnosis of VCI since the presence of focal signs is inappropriate, and stepwise progression is more supportive than diagnostic of VCI. The purpose of defining the new concept of VCI is to identify preventable risk factors. Importantly, not only physical health but also mental health should be monitored and treated.

Aged↗
PubMed2002

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.

Aged↗
PubMed2002

Frailty, fitness and late-life mortality in relation to chronological and biological age.

BACKGROUND: People age at remarkably different rates, but how to estimate trajectories of senescence is controversial. METHODS: In a secondary analysis of a representative cohort of Canadians aged 65 and over (n = 2914) we estimated a frailty index based on the proportion of 20 deficits observed in a structured clinical examination. The construct validity of the index was examined through its relationship to chronological age (CA). The criterion validity was examined in its ability to predict mortality, and in relation to other predictions about aging. From the frailty index, relative (to CA) fitness and frailty were estimated, as was an individual's biological age. RESULTS: The average value of the frailty index increased with age in a log-linear relationship (r = 0.91; p < 0.001). In a Cox regression analysis, biological age was significantly more highly associated with death than chronological age. The average increase in the frailty index (i.e. the average accumulation of deficits) amongst those with no cognitive impairment was 3 per cent per year. CONCLUSIONS: The frailty index is a sensitive predictor of survival. As the index includes items not traditionally related to adverse health outcomes, the finding is compatible with a view of frailty as the failure to integrate the complex responses required to maintain function.

Journal Article↗
PubMed2002

Use of lipid-lowering agents, indication bias, and the risk of dementia in community-dwelling elderly people.

BACKGROUND: Recent reports suggest a possibly protective effect for statins in patients with Alzheimer disease. This association could be due to indication bias, i.e., people who elect to take lipid-lowering agents (LLAs) may be healthier than those who do not, so that it may be these other health factors that explain their lower risk of dementia. OBJECTIVES: To examine the association between the use of LLAs and dementia, adjusting for other markers of health, and to investigate factors associated with LLA use. DESIGN: A cohort study of LLA use and a case-control study of dementia in relation to LLA use, in a secondary analysis of the Canadian Study of Health and Aging. SETTING: A nationally representative population-based survey of Canadians 65 years and older. PARTICIPANTS: To examine features associated with statin use, we evaluated data on 2305 people for whom health information, drug use, and cognitive status were known. To examine the relationship between LLA use and dementia, we selected incident cases of dementia (n = 492, of whom 326 had Alzheimer disease) that occurred between the first and second waves of the study. Control subjects were 823 persons examined during the first and second phases of the Canadian Study of Health and Aging who had no cognitive impairment. RESULTS: Use of LLAs was significantly (P<.001) more common in younger (65-79 years) than in older (> or = 80 years) people. It was not associated with other factors indicating a healthy lifestyle, but was associated with a history of smoking and hypertension. Use of statins and other LLAs reduced the risk of Alzheimer disease in subjects younger than 80 years, an effect that persisted after adjustment for sex, educational level, and self-rated health (odds ratio, 0.26; 95% confidence interval, 0.08-0.88). There was no significant effect in subjects 80 years and older. CONCLUSIONS: While the possibility of indication bias in the original observations cannot be excluded, it was not demonstrated in LLA use in this study. Lipid-lowering agent use was associated with a lower risk of dementia, and specifically of Alzheimer disease, in those younger than 80 years. Further research is warranted.

Age Factors↗
PubMed2002

Improving clinical descriptions to understand the effects of dementia treatment: consensus recommendations.

OBJECTIVES: To recommend how the description of clinically detectable treatment effects might be improved for antidementia drug trials. METHOD: Consensus conference, with review of available evidence. RESULTS: We suggest widespread, systematic, qualitative studies, based on prospective observations such as the clinicians' narrative descriptions of patient's changes used in the Clinician's Interview-Based Impressions of Change (CIBIC-Plus), plus caregiver input. The identification of patient and caregiver expectations, and an understanding of how these expectations are met, are proposed as priorities for future study. CONCLUSION: Better descriptions of treatment effects can enhance our understanding of both clinical meaningfulness and cholinergic function in the brain.

Aged↗
PubMed2002

Relation between butyrylcholinesterase K variant, paraoxonase 1 (PON1) Q and R and apolipoprotein E epsilon 4 genes in early-onset coronary artery disease.

OBJECTIVES: The common K variant of butyrylcholinesterase (BChE-K), an enzyme which metabolizes acetylcholine and organophosphates, has been associated with Alzheimer's disease, especially in the presence of the apolipoprotein E epsilon 4 allele (APOE-epsilon 4). Although APOE-epsilon 4 has been associated with the development of coronary artery disease (CAD), an association between the BChE-K variant and CAD has not been explored. Paraoxonase 1 (PON1), located within HDL, is an enzyme which also metabolizes organophosphates and may be antiatherogenic. The R192 variant of PON1 (PON1-R) has been associated with CAD. DESIGN AND METHODS: To determine whether BChE-K is also associated with premature CAD, we examined the frequency of BChE-K among patients with early-onset CAD (n = 150; < 50 yr) vs. late-onset CAD (n = 150; > 65 yr) by molecular analysis. We also examined the frequency of the PON1-R allele in both groups, and explored whether there was synergism between BChE-K and APOE-epsilon 4, BChE-K and PON1-R or PON1-R and APOE-epsilon 4. RESULTS: The frequency of the BChE-K allele tended to be greater among early-onset CAD patients compared to late-onset CAD patients (41.3% vs. 31.3%; p = 0.07), but without any significant difference between males and females. There was no difference in the prevalence of the PON1-R allele between those with early- or late-onset CAD (46.0% vs. 52.7%; p = 0.25). Twenty-two patients with early-onset CAD had both the BChE-K plus APOE-epsilon 4 alleles (14.7%) compared to 11 late-onset CAD patients (7.3%) (p = 0.04). There was no such association between BChE-K and PON1-R, nor PON1-R and APOE-epsilon 4. CONCLUSIONS: Our study suggests that there is a minor association between BChE-K and early-onset CAD, especially in the presence of the APOE-epsilon 4 allele.

Age of Onset↗
PubMed2002

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.

Adolescent↗