Con: Can biomarkers be gold standards in Alzheimer's disease?

As Alzheimer's disease remains a clinical diagnosis, and as clinical diagnosis can be difficult, it makes sense to look for so-called biomarkers. A biomarker predicts who is likely to have the illness and who is not. Some biomarkers might even correlate with a clinically meaningful response to treatment. Developing biomarkers is often characterized as searching for a diagnostic gold standard that can seem appealing in its promise of certainty. Even so, considering both the economic history of the gold standard and the results of neuropathological studies, framing the search for measurable, biological correlates of dementia syndromes in this way is likely to be self-defeating. Instead of considering biomarkers as providing certainty through referent criterion validation, currently it makes more sense to test their construct validity and their predictive ability. This means that while biomarkers should inform, they will not dictate clinical meaningfulness. For the foreseeable future, even were they to inform diagnosis, biomarkers cannot substitute for understanding whether patients and caregivers find a given dementia treatment effective. Instead, clinicians should recognize their own determining role, both in dementia diagnosis and in the evaluation of treatment. These roles will best be executed by hearing what patients and caregivers tell us about dementia, and its response to treatment

Biomarkers to Measure Treatment Effects in Alzheimer's Disease: What Should We Look for?

It is often surprisingly difficult to tell whether a treatment for Alzheimer's disease is effective. Biomarkers might offer the potential of a quantifiable objective measure of treatment effectiveness. This paper suggests several criteria by which biomarkers might be evaluated as outcomes measures. These include biological plausibility, statistical significance, dose dependence, convergence across measures, and replicability. If biomarkers can meet these criteria, then, pending regulatory approval, they may have a role in the evaluation of treatment effectiveness in Alzheimer's disease. If not, their usefulness may be in supplementing, but not supplanting, clinical profiles of treatment effects

Exploring the relationship between geriatric patients and their carers through portraiture: giving, receiving, observing & witnessing care (GROWing Care)

The process of creating a portrait relies on a series of intimate interactions. Portraits, even those that depict a single individual, are a visual testament to a relationship. Portrait sitters are required to engage with artists in the creation of their personal visual narrative. As viewers of a portrait, we are invited to actively participate in other’s stories, to observe, to question, even stare. This process is integral to the portraits evolving meaning. Giving, receiving, observing & witnessing care (GROWing Care), the case study presented in this manuscript, draws on these multiple exchanges to explore the experience of dementia and portraiture among older adults and their partners in care as they work with artist/researcher Mark Gilbert, and geriatrician, Kenneth Rockwood

Social Vulnerability, Frailty and Mortality in Elderly People

BACKGROUND:Social vulnerability is related to the health of elderly people, but its measurement and relationship to frailty are controversial. The aims of the present study were to operationalize social vulnerability according to a deficit accumulation approach, to compare social vulnerability and frailty, and to study social vulnerability in relation to mortality. METHODS AND FINDINGS:This is a secondary analysis of community-dwelling elderly people in two cohort studies, the Canadian Study of Health and Aging (CSHA, 1996/7-2001/2; N = 3707) and the National Population Health Survey (NPHS, 1994-2002; N = 2648). Social vulnerability index measures that used self-reported items (23 in NPHS, 40 in CSHA) were constructed. Each measure ranges from 0 (no vulnerability) to 1 (maximum vulnerability). The primary outcome measure was mortality over five (CHSA) or eight (NPHS) years. Associations with age, sex, and frailty (as measured by an analogously constructed frailty index) were also studied. All individuals had some degree of social vulnerability. Women had higher social vulnerability than men, and vulnerability increased with age. Frailty and social vulnerability were moderately correlated. Adjusting for age, sex, and frailty, each additional social 'deficit' was associated with an increased odds of mortality (5 years in CSHA, odds ratio = 1.05, 95% confidence interval: 1.02-1.07; 8 years in the NPHS, odds ratio = 1.08, 95% confidence interval: 1.03-1.14). We identified a meaningful survival gradient across quartiles of social vulnerability, and although women had better survival than men, survival for women with high social vulnerability was equivalent to that of men with low vulnerability. CONCLUSIONS:Social vulnerability is reproducibly related to individual frailty/fitness, but distinct from it. Greater social vulnerability is associated with mortality in older adults. Further study on the measurement and operationalization of social vulnerability, and of its relationships to other important health outcomes, is warranted

What Lawrence’s Story Tells Health Researchers About Arts-Based Interactions

In arts-based-research, knowledge and meaning emerge from people’s experiences of being in dynamic, ambiguous, intentional, and ethical relationships with each other and the arts. This case study draws on Launer’s “7 C’s” (context, conversations, curiosity, complexity, challenge, caution, and care) to understand the aesthetics (shape and form) and ethics of relationships between an artist-researcher and patient-sitter in portraiture-based medical research. This case supports the 7 C’s being embodied in the art-making process, as the approach can usefully frame ethical challenges and rewards of portraiture-based health research for artist-researcher and patient-participant

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

Fractal complexity of daily physical activity and cognitive function in a midlife cohort

High stability of fluctuation in physiological patterns across fixed time periods suggest healthy fractal complexity, while greater randomness in fluctuation patterns may indicate underlying disease processes. The importance of fractal stability in mid-life remains unexplored. We quantified fractal regulation patterns in 24-h accelerometer data and examined associations with cognitive function in midlife. Data from 5097 individuals (aged 46) from the 1970 British Cohort Study were analyzed. Participants wore thigh-mounted accelerometers for seven days and completed cognitive tests (verbal fluency, memory, processing speed; derived composite z-score). Detrended fluctuation analysis (DFA) was used to examine temporal correlations of acceleration magnitude across 25 time scales (range: 1 min-10 h). Linear regression examined associations between DFA scaling exponents (DFAe) and each standardised cognitive outcome. DFAe was normally distributed (mean ± SD: 0.90 ± 0.06; range: 0.72-1.25). In males, a 0.10 increase in DFAe was associated with a 0.30 (95% Confidence Interval: 0.14, 0.47) increase in composite cognitive z-score in unadjusted models; associations were strongest for verbal fluency (0.10 [0.04, 0.16]). Associations remained in fully-adjusted models for verbal fluency only (0.06 [0.00, 0.12]). There was no association between DFA and cognition in females. Greater fractal stability in men was associated with better cognitive function. This could indicate mechanisms through which fractal complexity may scale up to and contribute to cognitive clinical endpoints