BMJ No 7115 Volume 315
Clinical Review Saturday 25 October 1997
Recent advances
Geriatric medicine
Marco Pahor, William B Applegate
The primary aims of geriatric medicine are to relieve suffering in old people and to increase the number of years free of disability that they can enjoy. Here we focus on new evidence about the benefits of interventions commonly used in geriatric medicine.
We decided to focus on clinical interventions because of their importance to clinicians. We then selected the interventions that we judged (as editors of the Journal of the American Geriatrics Society) to be the more important ones dealt with in the English language medical journals in the past 18-24 months. We carried out thorough Medline searches on each intervention selected. In this article we have chosen a "lifetime" perspective; we have covered new studies whose subjects included middle aged people because the interventions are relevant to disorders related to aging.
| Recent advances |
| Chronic inflammation has a key role in the abnormal processes related to aging, including changes in body composition, congestive heart failure, and possibly dementia |
| Increasing oxidative stress is a key aspect of aging. Studies suggest that vitamin E supplementation reduces coronary events associated with atherosclerosis and slows the processes underlying Alzheimer's disease |
| Control of high systolic blood pressure is important in preventing stroke |
| Targeted and coordinated home health care can improve the health of older people with chronic disease and reduce admissions to hospital |
Non-steroidal anti-inflammatory drugs
Their role in dementia and cancer
Cardiovascular disease Anti-inflammatory or antiplatelet effects Importance of inflammation
Balancing risks and benefits Antioxidant vitamins and heart disease These favourable findings were not confirmed in a Finnish trial whose
subects were 1,862 male smokers aged 50-69 years who had had a
myocardial infarction.(21) The men were randomised to
receive vitamin E (50 mg/day), beta carotene (20 mg/day), both
vitamins, or placebo. After a median follow up of 5.3 years the four
groups had similar rates of major coronary events. Use of low doses or
different sources of vitamin E (synthetic compared with natural) might
have accounted for the differences in results between this study and
Cambridge heart antioxidant study. Participants randomised to receive
beta carotene had significantly higher rates of coronary deaths.
Vitamin E and the immune response ß Carotene and vitamin C Antihypertensive treatment and heart disease Several studies indicate that lowering systolic blood pressure and
maintaining control of blood pressure by any class of medication for
hypertension is better than placebo for preventing stroke. In a recent
meta-analysis, treatment with diuretics given in low doses to older
adults was associated with reduced risks of stroke, coronary heart
disease, congestive heart failure, and total mortality.(31)
Trials to determine which antihypertensive drugs are better at
preventing major complications of hypertension continue in both the
United States and Europe.
Antihypertensive treatment and dementia Various studies of exercise programmes have shown that some can
improve balance.(36) Programmes which emphasise resistance
exercises for the legs are particularly useful in helping older people
rise from a chair and increase their walking speed.(37) The
addition of upper body resistance exercises increases the range of
activities of daily living (for example, carrying groceries) which
older people can perform, and flexibility exercises may help protect
against falls.(37)
Evidence continues to mount that home health care has a
profound impact on older people who are frail and have chronic disease.
Studies by Rich and colleagues have shown the benefit of home health
care on patients with congestive heart failure.(38) A recent
study has shown that home counselling of carers results in a lower rate
of admission to nursing home in people with Alzheimer's
disease.(39) In addition, a recent randomised controlled
trial of the impact a psychogeriatric team had on elderly people living
at home indicated that intervention in the home reduced the level of
depression in this group (relative risk 0.33; 0.1 to
0.5).(39) Analyses indicate that the people who were given
home care were more likely to start and continue treatment with
antidepressant drugs, to have a review of social function with
counselling, and to have professional support of interaction with
family.(40) However, a randomised controlled trial of
specialist nurse support at home for patients with stroke showed little
benefit - a small improvement in social activities, and this only in
patients who were moderately disabled.(41) A long term
follow up study of patients with urinary incontinence has shown that
counselling by a nurse in primary care settings is effective: after
four years, urinary incontinence was still improved in most study
subjects.(42)
Little is known about the primary factors leading
to disability in older people. Large cohort studies funded by the
National Institute on Aging in the United States, such as the women's
health and aging study and the health and body changes study, seek to
identify risk factors of progressive and incident disability. The
findings of these studies will help to target the interventions to be
tested in older people in randomised clinical trials.
Department of
Preventive Medicine,
Correspondence to:
Dr Pahor
Funding: No external funding.
(Accepted 28 August 1997)
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Non-steroidal anti-inflammatory drugs are used mainly to
control pain and inflammation, but they may also protect from dementia
and cancer. Two observational studies in cohorts of elderly
subjects - the established populations for epidemiologic studies of the
elderly and the Baltimore longitudinal study on aging - have shown that
long term use of non-steroidal anti-inflammatory drugs is associated
with improved cognitive function and a reduced risk of Alzheimer's
disease.(1-2) A case-control study found that the regular
use of aspirin or other non-steroidal antiinflammatory drugs such
as ibuprofen, indomethacin, naproxen, and piroxicam was related to a
reduced risk of breast cancer.(3) However, a large cohort
study found no such association with aspirin.(4) Another
case-control study in people of m
New data support the benefits of aspirin in cardiovascular
disease, which is still the most common cause of death and disability
in older people. The international stroke trial and the Chinese acute
stroke trial showed that giving aspirin shortly after an ischaemic
stroke reduced the risk of death or recurrent stroke for up to 4 weeks
and 6 months of follow up respectively.(8-9) These
randomised trials have included more than 40,000 subjects; 84% in the
international stroke trial and 68% in the Chinese acute stroke trial
were aged 60 years or more. Aspirin was associated with a 12%
reduction in risk in the international stroke trial and a 9% one in
the Chinese trial.
Until recently the beneficial effect of aspirin in coronary
disease has been attributed mainly to its antiplatelet effects. Data
are accumulating on the role of inflammation in atherosclerosis, and
these suggest that aspirin may inhibit inflammation. In subjects aged
40-84 years enrolled in the physician's health study, the baseline
concentration of plasma C reactive protein, a marker of systemic
inflammation, predicted the occurrence of myocardial infarction or
ischaemic stroke.(10) The reduction in the risk of acute
myocardial infarction associated with taking aspirin was greater in
people with high concentrations of C reactive protein than in those
with low values.
In older people, the impact of inflammation may be widespread, and
it may have important implications for their physical function and
disability. Recent studies have highlighted the association of
proinflammatory cytokines such as tumour necrosis factor alpha and
interleukin 6 with a poor prognosis and increased severity of heart
failure.(11-12) Excess cytokine production is also
associated with a loss of skeletal muscle and cachexia that accompanies
heart failure.(13) Whether generalised inflammation causes
changes in body composition and accounts for the excess morbidity
related to aging is being investigated in a long term cohort study of
3,000 older people being conducted in the United
States.
The current evidence is insufficient to recommend the use of
non-steroidal anti-inflammatory drugs in the prevention of dementia or
cancer. Older people are more likely to have side effects such as acute
renal failure, gastrointestinal perforation, and gastrointestinal
bleeding.(14-16) Recent data indicate that among individual
non-steroidal anti-inflammatory agents, low dose ibuprofen is least
likely to cause gastrointestinal complications; that buffering or
enteric coating of aspirin does not protect against upper
gastrointestinal bleeding; and that famotidine prevents gastric and
duodenal ulcers caused by non-steroidal anti-inflammatory
drugs.(16-18)
Oxidative stress
Vitamin E and dementing illnesses
Oxidative stress is one mechanism involved in aging. New
findings show the effects of antioxidants on the health of people of
various ages. In a two year randomised placebo controlled trial, 2000
IU of vitamin E per day given to patients with moderate Alzheimer's
disease delayed by 50% the combined end point of death, admission to
an institution, inability to perform the activities of daily living, or
severe dementia.(19) In the same study a similar effect was
obtained with selegiline alone or with selegiline and vitamin E
combined (fig 1).
In the Cambridge heart antioxidant study, 2,002 patients with
coronary heart disease were randomised to receive vitamin E (400-800 IU
per day) or placebo, and were followed up for a median time of 1.4
years.(20) The mean age of the study participants was 61.8
years. In the active treatment group, the combined end point of death
from cardiovascular causes or non-fatal myocardial infarction was
significantly reduced (relative risk 0.53; 95% confidence interval
0.34 to 0.83). 
Fig 1: Survival free of adverse events - death,
admission to an institution, loss of the ability to perform activities
of daily living, or severe dementia - in patients with Alzheimer's
disease assigned to treatment with alpha tocopherol, selegiline, alpha
tocopherol and selegiline, or placebo. Effects for all three active
treatments were significant when compared with placebo (P=0.012,
P=0.001, P=0.049, respectively). Reproduced with
permission(19)
In a fourth trial, 88 healthy people aged 65 years or older were
randomised to receive vitamin E (60 IU per day, 200 IU per day, or 800
IU per day) or placebo.(22) After four months of follow up,
those who had taken vitamin E supplements showed a significant
improvement in the indices of immune response mediated by T cells. The
benefits of vitamin E are not limited to pharmacological
supplementation. One observational study followed 34,486
postmenopausal women (mean age 61.5 years) who had a high dietary
intake of vitamin E. After seven years they showed a significantly
reduced risk of death from coronary heart disease.(23)
Intake of vitamins A and C was not associated with the risk of death
from coronary heart disease.
Selenium
A randomised placebo controlled clinical trial (subjects' mean
age 63.2 years, range 18-80 years) (fig 2) found that selenium, another
antioxidant micronutrient, may protect against all cancers, and a
case-control study (subjects' mean age 53.1 years) found that it may
protect against ovarian cancer.(24-25) These findings need
confirmation, however, since death from all forms of cancer was not the
primary end point of the first trial and the association with several
micronutrients was tested in the case-control
study.
Fig 2: Kaplan-Meier curve of deaths from all forms of
cancer in patients with skin cancer who were randomised to treatment
with selenium or placebo (P=0.001). Reproduced with
permission(24)
The results of supplementation with beta carotene are less
favourable. A randomised trial in 22,071 male doctors aged 40 to 84
years found that beta carotene had no effect on the incidences of cancer
and cardiovascular disease after 14 years of follow up.(26)
In a trial in which 18,314 smokers (mean age 57.5 years) participated,
the combination of beta carotene and vitamin A increased the risk of
death from lung cancer (relative risk 1.28; 1.04 to 1.57) and from all
causes (1.17; 1.03 to 1.33) and tended to increase the risk of death
from cardiovascular disease (1.26; 0.99 to 1.61). Another trial, the
beta carotene and retinol efficacy trial, in 18,314 men and women
(mean age 58 years) has been stopped early because the incidence of and
mortality from lung cancer was excessive.(27) A recent
cohort study in Finnish men aged over 60 has shown that vitamin C
deficiency, assessed by a low plasma ascorbate concentration, is a risk
factor for coronary heart disease.(28) However, it is
not known whether supplementation with vitamin C reduces the
risk.
Hypertension
The impact of medication for high blood pressure has been
clarified with regard to intermediate major cardiovascular outcomes,
such as stroke, coronary heart disease, and congestive heart failure.
However, the effect of antihypertensive treatment on more long term
degenerative disorders such as dementia and disability is less clear.
Findings from the non-randomised Shanghai trial of nifedipine in the
elderly(29) and the recent report of the Syst-Eur
Trial(30) replicate and extend the findings of the systolic
hypertension in the elderly program with regard to patients with
isolated systolic hypertension or predominant systolic hypertension for
the outcome of stroke. As was found for the regimen based on diuretic
drugs in the systemic hypertension in the elderly program, both of
these more recent trials show that giving a dihydropyridine calcium
channel blocker to older people who have predominantly systolic
hypertension decreases the rate of stroke when compared with placebo
(relative risk in Shanghai trial 0.3 (0.24 to 0.77); in Syst-Eur trial
0.58, P=0.003).
Data from the systolic hypertension in the elderly program show that
diuretic drug treatment of isolated systolic hypertension in patients
with moderate type II diabetes was at least as effective as treatment
with other types of antihypertensive drugs in reducing stroke (relative
risk 0.78; 0.45 to 1.34), non-fatal myocardial infarction and coronary
heart disease (0.46; 0.24 to 0.88), and all major cardiovascular events
(0.66; 0.46 to 0.94).(32) In addition, a recent publication
from the same group has shown that treating isolated systolic
hypertension with diuretic drugs can reduce the risk of heart failure
over time (0.51; 0.37 to 0.71, P0.0001). The reduction in congestive
heart failure events is greatest in patients with a history of
myocardial infarction or electrocardiac evidence of this (0.19; 0.06 to
0.53, P=0.002). Although smaller, the reduction was also seen in people
without evidence of a previous myocardial infarction (fig
3).(33) 
Fig 3: Heart failure events in the systolic
hypertension in the elderly program in relation to the following
treatment groups: A=placebo with a baseline history of myocardial
infarction (by personal history or electrocardiogram); B=active
treatment with a baseline history of myocardial infarction; C=placebo
without a baseline history of myocardial infarction; and D=active
treatment without a baseline history of myocardial infarction.
Reproduced with permission(33)
The effect of antihypertensive treatment in elderly people on
another long term outcome - dementia - is less than certain. In the
Medical Research Council's treatment trial of hypertension in older
adults, treatment of moderate hypertension had no impact on cognitive
function.(34) However, analyses of data from the Kungsholmen
project, seem to show that Alzheimer's disease is associated with a
decrease in both systolic and diastolic blood pressures.(35)
Data available to date do not support the suggestion that lowering the
systolic or diastolic blood pressure in older people has any effect on
cognitive function or the subsequent development of dementia. In
addition, the data from Kungsholmen are not definitive and a major
study is still needed.
Exercise programmes
Home health care
Factors in disability
University of Tennessee,
Memphis,
TN 38105,
USA
Marco Pahor,
associate
professor
William B
Applegate,
professor
Conflict of interest: None.
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