frailty in elderly

review of frailty in elderly in the recent lancet (see geriatrics frailty lancet 2013 in dropbox). a bit hard to define frailty, but mostly has to do with increased vulnerability, with disproportionately large changes from small insults (eg new drugs, minor infections). seems to be an accumulation of molecular and cellular damage from many mechanisms over time.  one recent study found that in assessing 12 measures of dysfunction in 6 different systems, abnormal results in 3 or more systems was more predictive of frailty, and, specifically, the number of abnormal systems was more predictive than abnormalities in any particular system (i have seen several older people with small, potentially reversible problems in several different organ systems -- a little heart failure, renal dysfunction, infection -- and i anticipated being able to fix each one, but with the multi-system issues in aggregate the patients have done poorly). so, a few issues in the article.

--frequent clinical presentations of frailty:

    --extreme fatigue, unexplained wt loss, frequent infections

    --falls (balance and gait impairments are common. other risk factors for falls include vision, strength changes)

    --delirium (acute confusion) common, with approx 30% of elderly in hosp with delirium and point prevalence in long-term care of 15%

    --fluctuating disability: some days are fine, others requiring lots of care

    --systems involved include

        --frail brain: disproportionate effect of aging on neurons with high metabolic demand (eg hippocampus, resulting in difficulty creating new memories)

        --frail endocrine system: dec in growth hormone, estradiol/testosterone, activity of adrenocortical cells (dec DHEA and DHEA-S, but with gradual increase in cortisol release). repletion of these hormones finds mixed results, so these findings may be associated but not causal. the cortisol one, however, may be important (higher cortisol potentially leading to increased catabolism, muscle mass loss, anorexia, wt loss, fatigue and perhaps effects on depleting hippocampal cells)

        --frail immune system: dec Tcells, blunting of B cell antibody response, dec natural killer cells, dec phagocytosis. several cytokines assoc with frailty, including IL-6, CRP, TNF-a

        --frail skeletal muscles: progressive loss of muscle mass, strength

--models of frailty:

    --phenotype model: 5 variables: unintentional wt loss, self-reported exhaustion, low energy expenditure, slow gait speed, weak grip strength. those with 3 or more factors were "frail", 1-2 factors were "pre-frail". of 5200 in cardiovasc heart study over 65 yo, mortality at 7 years was 12% for non-frail, 23% for pre-frail and 43% for frail. impressive, but somewhat weird study, since these were five arbitrary factors and did not include other perhaps more intuitive factors, such as cognitive impairment.

    --cumulative deficit model: canadian study of health and aging looked at 92 baseline variables and gave 1 point for deficits in each one.  concept is that frailty is the process of accumulation of different deficits and not a simple cutpoint.  a specific value (0.67) identified frailty beyond which further deficits were not sustainable and very likely led to death. this tool is obviously unusable. subsequently whittled down to 30 items with same predictive value. again, this index predicted risk of death and institutionalization, but still not practical.

--instruments  (the above shows that there is an important clinical implication of frailty, and longterm decisions are best based on that, as opposed to chronological age)

    --several intuitive tests to assess frailty are not validated, such as timed-up-and-go test, hand-grip strength using a dynamometer, pulmonary function testing.  slow gait speed does characterize a group of elderly who are likely to develop adverse outcomes and had similar accuracy to a complex multivariate assessment model.

    --Edmonton Frail Scale includes timed-up-and-go test and test for cognitive impairment, takes less than 5 minutes, and is valid, reliable, and doable by non-geriatricians, though they comment that "its diagnostic accuracy has not been investigated".

--interventions 

    --frail elderly in comprehensive geriatric inpatient wards do better (more likely to return home, less cognitive or functional decline, lower mortality rates in hospital)

    --exercise can improve outcomes of mobility and functional ability

    --cochrane review of 49 RCTs found that interventions which focus on strength and balance training can increase muscle strength and functional abilities, though the studies are mixed (eg, one study of 100 pts found no effect of a nurtritional and exercise program on strength, gait speed, stair climbing)

--meds:

    --ACE-i improve skeletal muscle structure and function and may slow the decrease of muscle strength with age.  testosterone helps muscles but too many adverse effects (cardiorespiratory). vit d helps, and combo of ca/vit d reduces fractures in some studies

so, difficult situation. we have an aging population with increasing frailty. definition of frailty still not entirely clear. assessment of frailty unclear, and there needs to be a consensus approach/tool which is usable in the primary care setting and does not take much time. a few interventions seem to help some. goal, of course, would be to identify early markers of impending frailty and intervene to prevent progression.