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Differential dx tips
Alzheimer's disease
Distinguishing features: Progressive worsening
of memory and other cognitive functions with no
disturbance of consciousness.
Vascular dementia
Distinguishing features: Onset of dementia within
three months of recognized stroke with abrupt
deterioration, or fluctuating, stepwise progression
of cognitive deficits.
Dementia with Lewy bodies
Distinguishing features: Fluctuating cognition
with pronounced variations in attention and alertness
recurrent visual hallucinations; spontaneous motor
features of parkinsonism; REM sleep behaviour
disorder.
Frontotemporal dementia
Distinguishing features: Character changes and
disordered social conduct; perception, spatial
skills and memory are usually unaffected; insidious
onset and gradual progression.
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In our last issue (click
here to see part 1), we explored some of the common
pitfalls in the early diagnosis of dementia. Here, we
examine the challenge of making a differential diagnosis.
It's been exactly 100 years since
Alois Alzheimer diagnosed his first patient, Auguste
D, with the disease that now bears his name. Dementia
is no longer considered the normal seventh age of man,
a "second childishness and mere oblivion," but rather
an umbrella term for an increasingly complex range of
diseases. One of the biggest hurdles facing the physicians
who treat dementia is not only figuring out which form
of the disease their patient has, but also figuring
out if it's even worth the trouble when there's such
a dearth of available treatments.
MIXED
BAG
"Identifying the specific cause of dementia is quite
a challenge," admits Dr Lonn Myronuk, a geriatric psychiatrist
in Parksville, BC. "We go on clinical grounds and do
the best we can." But he's adamant that it's absolutely
necessary to try. "It's about furthering our understanding
of why patients respond [to treatment] the way they
do and also to give families as much information as
possible about how we might expect the disease to progress.
I feel obligated to get as clear an idea as I can exactly
what's going on."
The four most common clinical presentations
of dementia are AD, vascular dementia (VD), dementia
with Lewy bodies (DLB) and frontotemporal dementia (FTD).
Each has its own characteristic features (see "Differential
Dx tips," right), but the lines between them are often
blurred.
AD, for example, accounts for 64%
of all dementias, according to the Alzheimer Society
of Canada. But more and more patients are being diagnosed
with what's known as "mixed dementia" — a combination
of AD and VD, which results from one or many strokes.
"It depends where you draw the line in the sand, but
some say as many as two thirds of patients with AD actually
have mixed dementia," says Dr Myronuk. Many view mixed
dementia as a continuum, with pure AD at one end and
VD at the other, and most patients falling somewhere
in the middle.
OrDER
THAT SCAN
One of the most useful diagnostic tools for teasing
out a differential diagnosis is imaging, says Dr Myronuk,
particularly when it comes to confirming if the patient's
had a stroke or if there's damage to the frontal or
temporal lobes. But their use remains controversial.
Dr David Conn, chief psychiatrist
at Baycrest in Toronto, says all his patients receive
a CT scan or MRI as part of their initial workup, but
notes that in general physicians don't always believe
it's worth the long wait time.
Dr Howard Feldman, director of
the UBC Clinic for AD and Related Disorders also thinks
imaging studies should be routine. "The argument against
it — that it's expensive or inaccessible —
doesn't hold in a world where we're still trying to
pull apart the contributing problems."
He's hopeful new research may eventually
give physicians the extra push to order a scan. One
of the most exciting areas of research, he says, is
the use of amyloid imaging to diagnose AD. "Ligands
that attach to amyloid or tau — important proteins
in the biology of the disease — may provide us
with the first opportunity to detect AD in vivo,"
he explains.
TREATMENT
OPTIONS
Once that elusive differential is more or less in the
bag, physicians can shift their focus towards treatment.
The best available are cholinesterase inhibitors (ChEIs).
By increasing levels of the neurotransmittor acetylcholine,
ChEIs are thought to improve cell-to-cell communication
in the brain. They've been trialled in AD, VD and DLB
and have shown some level of efficacy in all these forms.
Ironically, that's turned out to be a diagnostic double-edged
sword: since ChEIs are the standard of care in patients
with all three conditions, some physicians wonder why
they should bother with the differential. "If you're
directing your differential only towards treatment,
then it could be easy to think it doesn't really matter
what form of dementia your patient has," notes Dr Feldman.
But he stresses that it's still really important in
order to decide how to proceed with drug therapy.
For instance, we now know that
patients with DLB are typically the most responsive
to treatment with ChEIs. It's also one of the most rapidly
progressing forms of dementia, so getting patients on
treatment as soon as possible can make a real difference.
On the other hand, patients with
FTD don't respond to ChEIs at all. In these cases, selective
serotonin reuptake inhibitors (SSRIs) may be prescribed
to help relieve apathy and depression, while anti-psychotics
address hallucinations, delusions and aggression.
Dr Feldman also points out that
a minority of patients presenting with dementia could
actually be suffering from rarer conditions. He gives
the example of central nervous system vasculitis, which
has dementia-like symptoms of profound loss of memory
and concentration and an altered level of consciousness.
The available treatment — in this case, immunosuppressive
therapy — can save their life. "In these cases,
failure to proceed with a differential diagnosis can
actually be quite dangerous," he says.
KEEP
THE FAITH
The next big hurdle — for dementia experts and
GPs alike — is figuring out if it's worth putting
their demented patients on these meds. "I see a lot
of scepticism of the real world value of the drugs that
have come on the market," he says. Despite a century
of research, the response individual patients have to
treatment is varied and nearly impossible to predict.
Many physicians find it hard to "think positive."
Dr Feldman admits he falls in the
sceptics' camp. "My view on treatment is that the drugs
are effective in some but not all patients," he says.
"I don't believe there's any evidence that currently
available treatments can modify disease progression,
and if there is I'm not convinced. We're still learning."
Dr Myronuk is more optimistic.
He says the data shows the drugs really do work. "All
we can do is proceed with treatment and see what happens."
Dr Conn, too, is keeping the faith.
"Some patients get dramatic improvement, especially
early on," he says. "It's not curative but that doesn't
mean there aren't any benefits."
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