Changes in white matter as determinant of global functional decline in older independent outpatients: three year follow-up of LADIS (leukoaraiosis and disability) study cohort

We read with some interest Inzitari et al’s description of the
association
between white matter changes in older patients and subsequent functional
decline (1). This research suggests that there may exist novel occult
markers
of disease, and reinforces some of our intuition as clinicians dealing
daily
with the sort of patients described in the study. The patient group
described
is heterogenous and complex, and the study raises some other interesting
questions.

Firstly, while we note the protective effect of education on
subsequent
decline, it is interesting that the presence of osteoarthritis confers a
stronger
protection than a year of education, even when adjusted for other risk
factors.
The authors do not postulate a mechanism for this in the text. It is
possible
that the anti-inflammatory effect from the concomitant use of non-
steroidal
anti-inflammatory drugs (NSAIDs) conferred some benefit. COX-2 inhibitors
are well-known to increase cardiovascular risk (2), while the evidence of
harm
from non-selective NSAIDs is limited (3). Indeed, some beneficial effects
of
non-selective NSAIDs on cognitive decline, albeit contended, have been
noted
(4). Was medication use included in the data collected, and if so, were
there
associations between NSAID use or NSAID-class and progression to death or
disability? It is possible that issues of statistical power preclude a
definitive
answer to this question.

Secondly, if white matter changes contribute independently to
morbidity, as
this study suggests, it would be interesting to know if burden of white
matter
disease correlated with incident delirium in the study population. Such a
finding would go some way towards explaining relatively high rates of
delirium in older patients who were previously considered to be
cognitively
intact (5).

Finally, the composite rate of transition to disability or death of
15.8 per 100
person years serves to remind us that patients in the older age group who
seek medical attention – despite presenting as non-disabled – carry a high
-
risk of progression to unfavourable outcome. This should inform the
practice
of those of us – geriatricians and general physicians alike – who deal
with
older people in an increasingly rationed environment.

David Robinson (i), Diarmuid O’Shea (ii)

(i) Specialist Registrar in Geriatric Medicine, Royal Hospital,
Donnybrook,
Dublin 4

(ii) Consultant physician in Geriatric Medicine, St Vincent’s
University Hospital,
Dublin 4

1. Inzitari D, Pracucci G, Poggesi A, Carlucci G, Barkhof F, Chabriat
H, et al.
Changes in white matter as determinant of global functional decline in
older
independent outpatients: three year follow-up of LADIS (leukoaraiosis and
disability) study cohort. Bmj 2009;339:b2477.

2. Fosbol EL, Gislason GH, Jacobsen S, Folke F, Hansen ML, Schramm
TK, et
al. Risk of myocardial infarction and death associated with the use of
nonsteroidal anti-inflammatory drugs (NSAIDs) among healthy individuals: a

nationwide cohort study. Clin Pharmacol Ther 2009;85(2):190-7.

3. Roumie CL, Mitchel EF, Jr., Kaltenbach L, Arbogast PG, Gideon P,
Griffin MR.
Nonaspirin NSAIDs, cyclooxygenase 2 inhibitors, and the risk for stroke.
Stroke 2008;39(7):2037-45.

4. Rogers J, Sabbagh MN. Interactions of stroke, nonsteroidal anti-
inflammatory drugs, and APOE status in dementia risk. Neurology
2008;70(1):5-6.

5. Siddiqi N, House AO, Holmes JD. Occurrence and outcome of delirium
in
medical in-patients: a systematic literature review. Age Ageing
2006;35(4):350-64.

Competing interests:
None declared