From: sbharris@ix.netcom.com(Steven B. Harris)
Newsgroups: sci.med.nutrition
Subject: Re: Alzheimers & vitamins B-12 and Folic Acid Deficiencies
Date: 12 May 1998 22:28:23 GMT

In <B17DE764-AE69E@172.16.11.51> mmucica@weiderpub.com writes:
>
>I have a question regarding Alzheimers. Can you have no symptoms one
>day and then the next day have full blown Alzheimers? My father is 88
>and in the hospital and the first day he was given a pain pill and
>after receiving the pill had symptoms of forgetfulness, didn't care to
>eat, refused medicine and water, was belligerent -- a complete change
>of personality. I am familiar with the symptoms as my mother had
>Alzheimers. But can it come on so rapidly? One day having all your
>faculties and the next Alzheimers? A response will be greatly
>appreciated.


   In a word, yes.  The state is called "delerium."  It's possible to
be delerious without underlying dementia, but by far the largest
population of people who get delerius with stress (drugs, infections,
etc) are people at the very beginning of dementia.

   Unless you father had a stroke, it's very likely he'll eventually go
back to just the way he was before he entered the hospital, mentally.
But if you send him for careful mental testing, you may well find
evidence of beginning permanent cognative dysfunction (dementia).  You
may be unlucky and have this Alzheimer's (which may go slow or fast).
Or you may be lucky and find it's related to something fixable, such as
thyroid or B12 deficiency.  Have him seen by a geriatrician, if you can
find one.  A neuropsychologist if you can't.  Or both.

                                       Steve Harris, M.D.

From: sbharris@ix.netcom.com(Steven B. Harris)
Newsgroups: sci.med
Subject: Re: Paranoia and neuroleptics ?
Date: 6 Jul 1999 07:16:07 GMT

In <7lq2cg$fjs$1@news3.Belgium.EU.net> "DE WITTE Roland"
<roland.dewitte@ping.be> writes:

>I search a few references of recent works made about the way the
>neuroleptics are able to stop dementia in paranoia and schizophrenia.
>
>I am especially interested in works (with statistics) where the chemicals
>are use only during a short period.
>
>DE WITTE Roland


Comment:

    Neuroleptics (anti-psychotic drugs) are able to sometimes control
new symptoms of paranoia which resemble schizophrenia, which is a
result of dementia (ie, schizophrenic symptoms, such as paranoia and
delusions appear in old age, very unlike who average schizophrenic, who
has onset of symptoms in the teens or twenties).  Sometimes this
dementia/schizophrenia of old age is called "paraphrenia."

   The problem in dementia is partly an imbalance of cholinergic tone
to dopaminergic tone, as the cholinergic neurons are destroyed by the
dementing process more rapidly than other types.  Too much dopaminergic
tone can cause paranoia and frantic delusions (think of crack and speed
abusers).  Neuroleptics are anti-dopaminergic drugs.  They help the
paranoia and frantic emotional turmoil, but these "mental
straightjacket" drugs don't do anything for the dementia itself (memory
and intellectual impairment and personality changes), which continue to
progress.

   Neuroleptics are often used in dementia along with the anti-dementia
pro-cholinergic drugs (specifically, anti-cholinesterase drugs, such as
Aricept).  However, these latter drugs make some acute side effects of
neuroleptics, such as acute dyskinesia (stiffness and rigidity,
resembling Parkinson's disease) more apparent. (Surprise,
anti-dopaminergic drugs seem to bring on a disease which is treated by
giving a precuror to dopamine).  So one always ends up fighting for
balance.  In younger schizophenics, just as in Parkinson's disease
victims, ANTI-cholinergic drugs are often used to counteract these
dyskinetic symptoms of neuroleptics acutely.  One does not dare use
anticholinergics in the elderly demented, however, since they make the
dementia (especially memory problems) worse.  Many a slightly demented
elderly person has gone over the edge into complete inability to
function due to the anticholinergic effects of even over the counter
drugs, such as antihistamines (including the hidden ones, such as
Tylenol PM-- the geriatricians' least favorite OTC drug).

   As one would expect, the newer neuroleptics with less
anticholinergic properties and less risk (but not no risk) of
later tardive dykinesia, such as Remeron/mirtazepine, and
Risperidol, seem to make the best antipsychotics for demented
elderly with psychotic symptoms.  Tiny doses are used, and tardive
dyskinesia, which can be a permanent drug-induced condition, and which
the elderly (females especially) are more susceptible to, must be
carefully watched for.

From: "Steve Harris" <sbharris@ix.RETICULATEDOBJECTcom.com>
Newsgroups: sci.med
Subject: Re: dementia + self education
Date: Mon, 30 Jun 2003 14:42:09 -0700
Message-ID: <bdqari$n4u$1@slb1.atl.mindspring.net>

"Chris Fowler" <cfowler@linuxiceberg.com> wrote in message
news:1056986591.472738@minime.linuxiceberg.com...
> I have a grandmother-in-law that is now suffering from extremem
> dementia. I've always believed that disases like these in old age could
> be caused by a lack of self education during the life of the patient.


Ralph Waldo Emerson and Jonathan Swift both famously became
demented in old age. Get a better hypothesis.

Dementia is caused by a number of processes that kill
neurons. If you cut off the blood supply to small blocks of
brain so that they die, or you fill up the neurons with
toxic beta amyloid, why should it make a difference whether
or not those cells have been used to do calculus vs.
remember the names of soap opera stars? Either way, they're
dead.

The idea that if you think hard enough you won't get
demented is somewhat akin to the idea that if you drink hard
enough, your liver cells will have been too exercised ever
to get cancer. I'm sorry, but it doesn't follow. Perhaps a
better analogy is a exercise guru named Jim Fixx who thought
that anybody who could run a marathon was immune to heart
disease. He fell dead while jogging. His coronaries were all
nearly completely plugged.

SBH

From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med
Subject: Re: Alzheimer's and CXR
Date: 17 Aug 2005 12:24:01 -0700
Message-ID: <1124306640.991113.170790@f14g2000cwb.googlegroups.com>

Tom Salls wrote:
> Yes, this is a homework question. :)
>
> There's a whole range of tests which are performed on patients who are
> suspected to have Alzheimer's.  I can understand the rationale for most
> of them, but why is a CXR always included on those lists?  What other
> cause of dementia is being excluded by a CXR?  About the only thing I
> can think of is metastatic lung cancer, but that seems a bit of a long
> shot.

COMMENT:

If pulse ox is good and there's no fever, there's no reason for a CXR,
except to line somebody's pockets. Also no reason to do a CT, if an MRI
is available.

ONE MRI is needed (to rule out stroke, subdural hematoma, etc) if no
combined PET/CT is available, but often a PET/CT *IS* available (if you
want to take a long drive) but is not used because insurance won't pay
for it. So they end up doing 2 or more MRIs, futzing around with
dementia over the months or years, and all of which are far less useful
in making the diagnosis, and which together cost more than the
diagnostic single PET/CT would have! Diagnosis of type of dementia is
still a very inefficient and expensive system, still full of
inefficiencies, and arcane (but very expensive) technology which is
overused because insurrance and medicare have not caught up yet in what
they will pay for. The over-and-over MRI scanning of the chronically
confused elderly is one of the great screwups and scams of medicine
today.

SBH

From: David Rind <drind@caregroup.harvard.edu>
Newsgroups: sci.med
Subject: Re: Alzheimer's and CXR
Date: Wed, 17 Aug 2005 22:50:32 -0400
Message-ID: <de0t1u$q9$1@reader2.panix.com>

Tom Salls wrote:
> Yes, this is a homework question. :)
>
> There's a whole range of tests which are performed on patients who are
> suspected to have Alzheimer's.  I can understand the rationale for most
> of them, but why is a CXR always included on those lists?  What other
> cause of dementia is being excluded by a CXR?  About the only thing I
> can think of is metastatic lung cancer, but that seems a bit of a long
> shot.
>
> I am sure the answer is blatantly obvious, but I have rooted through
> K&C, Googled, and generally smacked my head against a brick wall for the
> last hour.
>
> Thanks for your time,
>
> Tom

Who recommends a CXR as part of a dementia workup? The list of tests
actually recommended by most groups for a dementia workup is actually
very short.

--
David Rind
drind@caregroup.harvard.edu

From: David Rind <drind@caregroup.harvard.edu>
Newsgroups: sci.med
Subject: Re: Alzheimer's and CXR
Date: Thu, 18 Aug 2005 19:33:40 -0400
Message-ID: <de35ss$bit$1@reader2.panix.com>

Tom Salls wrote:
> drind@caregroup.harvard.edu wrote:
>
>>Tom Salls wrote:
>>
>>>Yes, this is a homework question. :)
>>>
>>>There's a whole range of tests which are performed on patients who are
>>>suspected to have Alzheimer's.  I can understand the rationale for most
>>>of them, but why is a CXR always included on those lists?
>>
>>Who recommends a CXR as part of a dementia workup? The list of tests
>>actually recommended by most groups for a dementia workup is actually
>>very short.
>
>
> In real life, probably no one.  But I'm a student and so I'm at the
> level of regurgitating lists from my textbooks on demand.
>
> The list differs from textbook to textbook, but seems to run along the
> lines of: FBC, ESR, U&Es, blood glucose, LFTs, serum calcium, vitamin
> B12 & folate, TSH, T4, T3, syphilis serology, CXR, CT / MRI / SPECT /
> PET.
>
> I could see the rationale for each of those, but the CXR seemed rather
> out of place.
>
> Tom

In all seriousness, if you are using textbooks that are recommending
stuff like CXRs for dementia evaluation, you may want to consider
different textbooks/resources for this sort of clinical information.

--
David Rind
drind@caregroup.harvard.edu

From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med
Subject: Re: Alzheimer's and CXR
Date: 18 Aug 2005 19:18:44 -0700
Message-ID: <1124417924.422053.180720@g49g2000cwa.googlegroups.com>

Tom Salls wrote:
> In real life, probably no one.  But I'm a student and so I'm at the
> level of regurgitating lists from my textbooks on demand.
>
> The list differs from textbook to textbook, but seems to run along the
> lines of: FBC, ESR, U&Es, blood glucose, LFTs, serum calcium, vitamin
> B12 & folate, TSH, T4, T3, syphilis serology, CXR, CT / MRI / SPECT /
> PET.
>
> I could see the rationale for each of those, but the CXR seemed rather
> out of place.


COMMENT:

Well, welcome to the real world. There's a lot of mythology associated
with cases of "reversable dementia" (ie, cases of supposedly demented
people who were actually suffering from something treatable, and wound
up being magically cured by some Dr. House). But in the real world, if
that ever happens it's either because the diagnosis of dementia had
been prematurely applied to delirium, or else it was a case of somebody
in the early stages of dementia, who'd been temporarily pushed over
into worse dementia by the delirium of some treatable illness (like
infection) which then went away when the stress was reversed. However,
such people do have detectable mental problems on close testing, and
are soon back with the real thing (bona fide dementia) under conditions
of no stress, and this time aren't fixable. It's much the same thing
with honeymoon onset of diabetes, or somebody being warned of growing
emphysema because his chest colds are so much worse than anybody
else's. People with mild dementia get much worse when infected, but
that hardly counts as a reversable dementia. It must means you made the
dianosis of Alzheimer's or multi-infarct dementia somewhat earlier.
Which is good (especially for MID which you can treat), but don't fool
yourself about perfectly undamaged brains just misbehaving for month
and months because of something fixable.

Does funny blood sugar make you demented?  No. Gross abnormalities can
make you delirious (short term cognitive impairment), but they never
last months. You either get better or you die. The same is true of most
of the nasty things that can go wrong with your CBC or LFTs. The B12
and the folate come from a *very* few case reports of somebody with
reversible dementia who was B12 or deficient, and in my humble opinion
do not warrent the millions upon millions spent looking at those
vitamins. If your folate isn't low enough to make you megaloblastic,
it's hard to imagine that it alone is screwing up your brain; there are
plenty of genuinely megaloblastic people who mentate fine.

The B12 is perhaps worth doing, but I've seen hundreds of abnormal B12s
in the elderly, without one case of reversable dementia from it yet.
Again, it seems unlikely that somebody has been demyelinated badly
enough to be demented, while still having a normal peripheral nerve
exam, if you can do one. It's probably cheaper to put EVERYBODY on 1 mg
of B12 a day for a few months--- that's a fraction of the cost of the
blood test. But I'll conceed this one.

Does hyperthyroidism cause dementia?  No. It causes restlessness, and
looks a bit like infection. It's a hypersympathetic state. And it can
push mild dementia into worse dementia, much like infection. It is
rare, though. However, that said, T3 and T4 are now obsolete as screens
in the era of supersensitive TSH.

So what about TSH?  Well, everybody should have ONE TSH as a screen, I
suppose. Though most of these catch beginning Hashimoto's, and don't
really prevent or help treat dementia. *Does* HYPO-thyroidism cause
people to be demented?  Frankly, hardly ever. Hypothyroidism in
children causes cretinism and severe retardation (thus the bad rap),
but we're talking about low thyroid showing up first in the elderly.
Does it look like dementia?  No. Mild and moderately hypothyroid people
have slow mentation and feel like crap, but if nothing else is wrong
with their brains, so long as they awake, they are perfectly able to
read clocks, make change, and remember their own birthdates. Any
endocrinologist will tell you that-- the problem is the geriatricians
seem never to have spoken to the endocrine guys who actually see
hypothyroidism. If you get somebody with extremely low thyroid, about
to go into hypothyroid *coma,* that may not be true, but you'll
certainly recognize THAT from the rest of the physical exam. This is
not why we draw all those TSH's on bright-eyed Mrs. Jones who can't put
the numbers on a drawing of a clock face, or remember the names of her
children. This, you're not going to fix endocriologically. So it's a
waste of money.

I've talked about the CT and MRI. One or the other, never both. SPECT
is a good test when there's no PET available (it's poor man's PET). But
better to put somebody in car or even on a jet, and get the gold
standard PET/CT. It's worth every penny.

SBH

From: David Rind <drind@caregroup.harvard.edu>
Newsgroups: sci.med
Subject: Re: Alzheimer's and CXR
Date: Fri, 19 Aug 2005 18:14:56 -0400
Message-ID: <de5ll9$m4o$1@reader2.panix.com>

Tom Salls wrote:
> drind@caregroup.harvard.edu wrote:
>
>>In all seriousness, if you are using textbooks that are recommending
>>stuff like CXRs for dementia evaluation, you may want to consider
>>different textbooks/resources for this sort of clinical information.
>
>
> Thanks David.  As I said though, I am at the stage where I am learning
> the way we are 'supposed' to do it rather than what is actually done.
> This is the stuff that I will be expected to trot out in exams.
>
> The bible for clinical medicine over here is Kumar & Clark's "Clinical
> Medicine", which does recommend CXR to exclude secondary causes of
> dementia, although notes that dementia due to secondary causes is
> infrequent.  I'm sure that I'm going to run into plenty of things like
> this where the textbooks say one thing, but real life constraints
> dictate another.
>
> Cheers,
>
> Tom

I'm not sure what stage of training you're in exactly, but if a medical
student on morning rounds told me he'd ordered a CXR as part of a
dementia workup on a patient admitted the night before, I'd ask him to
justify it with more than a sentence in a book.

I've never been at a place where Kumar and Clark was considered the
bible of clinical medicine, and I have no opinion on it, but getting a
CXR for dementia is not an issue of what people really do versus what
the books say. Major texts (like Harrison's) do not recommend a CXR as
part of a dementia workup.

I'm pushing on this because you seem to have recognized that a CXR made
no sense (which caused your original post) and yet seem to be planning
to regurgitate this recommendation when asked (thus causing your fellow
students and perhaps some interns and residents to learn the wrong
workup for dementia) rather than planning to let people know that you
read the chapter that says this but can find no justification for the
recommendation. Honestly, if you get in trouble with some resident or
attending for questioning this sort of mistaken information in a book
that's a real problem.

If this is in the first two years and you're talking about paper exams
administered by nonclinicians, then I agree that the easier path may be
to answer the question as you've been taught, sadly.

--
David Rind
drind@caregroup.harvard.edu

From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med
Subject: Re: Alzheimer's and CXR
Date: 19 Aug 2005 15:30:15 -0700
Message-ID: <1124490615.622512.34700@z14g2000cwz.googlegroups.com>

Tom Salls wrote:
> sbharris@ix.netcom.com wrote:
> > Well, welcome to the real world. There's a lot of mythology associated
> > with cases of "reversable dementia" (ie, cases of supposedly demented
> > people who were actually suffering from something treatable, and wound
> > up being magically cured by some Dr. House).
>
> Thanks for that Steve, I appreciate you taking the time to go over all
> those tests - very useful.  It's quite entertaining the differences
> between what we're taught and what is actually done!
>
> Cheers,
>
> Tom


COMMENT:

Oh, bad news. I'm afraid what's actually DONE is usually what you're
reading in your textbook. And most of it is a terrific waste of money.
Not quite as bad as the serial MRIs done by some docs every time some
demented person has a small change in mental status--- but still a lot
of money down the rat-hole. And one reason why medicare and medicaid
are in serious danger of pulling us all under, in the good old US of A.

There are cases in medicine where really high tech stuff saves money.
For example, if you think treating AIDS is expensive with modern HAART
therapy, try treating as we did in the bad old days when all there was,
was AZT or nothing.

PET/CT is a little bit like that. It's a decent quality CT done in the
same machine as a PET (like the CDI REACT scanner), so you get a
"2-fer", plus much better quality on localizing the PET image, since
you can superimpose the images. It can make the diagnosis of
Alzheimer's and rule out mass lesions like large tumors or chronic
subdurals, in one swoop. And it's pretty good at telling you about
multi-infarct processes also, since to the extent that these cause
dementia, they affect frontal lobe metabolism and you see that directly
on 19-FDG PET, just as you do on SPECT.

Remember, the reason you image the head in dementia is to get
information to rule out chronic subdural hematoma, tumor, and
hydrocephalus. These all increase intercranial pressure and so affect
the whole brain. Strokes
don't do that. And strokes don't cause dementia unless there are very
many of them. You can get all the gross info from a CT.

People do MRIs on demented people to look for diffuse white matter
changes and vascular dementia, but this is usually a mistake, because
the truth of the matter is that these aren't very specific. You can see
them in non-demented people too. You're looking for their *metabolic
effect,* in working up dementia and PET tells you that directly. In
theory, the newer MRI techniques (functional or fMRI) can also, but
using fMRI to evaluate dementia is still in the research phase. What's
actually being *done* out there, is to use conventional MRI on
dementia, and conventional MRI is not sensitive OR specific. PET picks
up Alzheimer's LONG before anything shows up on MRI, and PET will also
tell you if vascular changes in MRI are likely to be dementing or not,
by looking at cortical metabolism. So all of that doesn't leave much
place for the standard MRI at all--- yet it's still the most common
modality used on demented patients. In fact, it's often used again and
again and again on them. People have such a terrible urge to look
inside the head to see if there's anything grossly wrong, that they'll
do it over and over, even if they know they'll usually see nothing of
value. So long as they're not paying for it (a similar thing happens in
low back pain).

You will find that head imaging, particular MRI, is used often to
substitute for the careful neurological exam, which takes time that
nobody wants to pay the clinician for (but there's no escaping paying
for the MRI). And this is particularly egregious in dementia, where the
workup is slow and the medicare payments to the clinician are small.
But even here the system could save a lot of money if people would pay
attention to even the gross things. For example, the demented elderly
person with the shuffling gait might have any possible cause for
dementia, but the demented elderly person with a good well-coordinated
gait (and there are many of these) almost certainly does NOT have
vascular dementia (aka multi-infarct dementia). Yet another reason to
save yourself that useless MRI, which will at best will only tell you
the same, and at worst will confuse you by showing you incidental white
matter disease which isn't causing the dementia you see clinically.

Steve


1:Top Magn Reson Imaging. 2004 Dec;15(6):369-89.

Pathological aging of the brain: an overview.

Bastos Leite AJ, Scheltens P, Barkhof F.

Department of Radiology, Vrije Universiteit (VU) Medical Center,
Amsterdam, the Netherlands. A.bastosleite@vumc.nl

The number of elderly people is increasing rapidly and, therefore, an
increase in neurodegenerative and cerebrovascular disorders causing
dementia is expected. Alzheimer disease (AD) is the most common cause
of dementia. Vascular dementia, dementia with Lewy bodies, and
frontotemporal dementia are the most frequent causes after AD, but a
large proportion of patients have a combination of degenerative and
vascular brain pathology. Characteristic magnetic resonance (MR)
imaging findings can contribute to the identification of different
diseases causing dementia. The MR imaging protocol should include axial
T2-weighted images (T2-WI), axial fluid-attenuated inversion recovery
(FLAIR) or proton density-weighted images, and axial gradient-echo
T2*-weighted images, for the detection of cerebrovascular pathology.
Structural neuroimaging in dementia is
focused on detection of brain atrophy, especially in the medial
temporal lobe, for which coronal high resolution T1-weighted images
perpendicular to the long axis of the temporal lobe are extremely
important. Single photon emission computed tomography and positron
emission tomography may have added value in the diagnosis of dementia
and may become more important in the future, due to the development of
radioligands for in vivo detection of AD pathology. New functional MR
techniques and serial volumetric imaging studies to identify subtle
brain abnormalities may also provide surrogate markers for pathologic
processes that occur in diseases causing dementia and, in conjunction
with clinical evaluation, may enable a more rigorous and early
diagnosis, approaching the accuracy of neuropathology.

PMID: 16041289 [PubMed - in process]

2: Dement Geriatr Cogn Disord. 2005 May 20;20(2-3):63-70 [Epub ahead of
print]

Diagnostic Value of FDG-PET and HMPAO-SPET in Patients with Mild
Dementia and Mild Cognitive Impairment: Metabolic Index and Perfusion
Index.

Dobert N, Pantel J, Frolich L, Hamscho N, Menzel C, Grunwald F.

Department of Nuclear Medicine, University of Frankfurt, Frankfurt,
Germany.

Objective: The diagnostic potential of F-18-2-fluoro-2-deoxy-D-glucose
positron emission tomography (PET) and technetium-99m
hexamethylpropylene amine oxime single-photon emission tomography
(SPET) in early detection and differential diagnosis of early dementia
was evaluated including a comparison of metabolic and perfusion indices
(PI). Methods: Twenty-four patients with initial clinical suspicion of
beginning dementia were examined, 12 of them with mild cognitive
impairment. All patients underwent SPET and PET within 2 weeks. Data
were compared with the final clinical diagnosis at follow-up - 9 with
Alzheimer's disease (AD), 1 with frontotemporal dementia, 1 with
vascular dementia (VD), 7 with mixed type of dementia (MIX) and 6
without any type of dementia. Metabolic
indices (MI) and PI were compared with each other. The regional
cerebral blood flow difference (rCBFdiff) calculated as local uptake
difference between the right and left hemisphere was measured for
patients with VD and MIX. Results: PET showed higher sensitivity and
specificity in identifying the different types of early dementia (44-91
and 78-89%, respectively) than SPET (11-64 and 79-89%, respectively),
especially in detecting AD (sensitivity 44%, specificity 83%) and MIX
(sensitivity 71%, specificity 78%). Especially in patients with mild
cognitive impairment, PET was the superior imaging modality for
predicting dementia. Using PET, dementia could be excluded in all
patients who did not develop dementia during the follow-up. In all
patients, a weak correlation between PI and MI was observed (rho =
0.64, p < 0.002). The rCBFdiff in patients
with VD and MIX ranged from 7 to 37%. Conclusion: In this study on
patients with initial suspicion of beginning dementia who underwent
both imaging modalities, PET and SPET, PET was the superior imaging
method, especially in the detection of early AD or MIX. Copyright (c)
2005 S. Karger AG, Basel.

PMID: 15908747 [PubMed - as supplied by publisher]


3: Nucl Med Commun. 2005 Mar;26(3):189-96.

Emission tomography in dementia.

Pakrasi S, O'Brien JT.

Institute for Health and Ageing, Wolfson Research Centre, Newcastle
General Hospital, Newcastle upon Tyne, NE4 6BE, UK.
sanjeet.pakrasi@ncl.ac.uk

Dementia is a chronic brain syndrome with enormous impact on health care
provision. Emission tomography (single photon emission computed
tomography (SPECT) and positron emission tomography (PET)) provides a
unique tool to investigate functional and neurochemical changes, both in
those with established dementia and in those at risk of subsequent
cognitive decline. Alzheimer's disease is characterized by bilateral
temporoparietal hypoperfusion on SPECT and hypometabolism on PET, which
may precede the onset of dementia as similar changes can be demonstrated
in those with mild cognitive impairment and in those genetically at risk
of developing Alzheimer's disease. In dementia with Lewy bodies medial
parietal and occipital perfusion deficits are seen together with
pre-synaptic and post-synaptic dopaminergic changes, most particularly a
reduction in the striatal pre-synaptic dopamine transporter which can be
visualized using appropriate ligands (e.g., (123)I-FP-CIT). Vascular
dementia is associated with multiple, asymmetric, perfusion deficits in
multi-infarct dementia. In contrast, subcortical vascular dementia is
associated with reduced perfusion but preserved oxygen extraction
fraction on PET.  Fronto-temporal dementia is characterized by both
hypometabolism and hypoperfusion in fronto-temporal lobes, though
hypometabolism appears more extensive, affecting large areas of the
cerebral hemispheres.  Longitudinal studies of treatment response in
Alzheimer's disease with cholinergic drugs have found changes in regional
blood flow and nicotinic and muscarinic receptor function in those
patients who respond to treatment. Currently, emission tomography is
widely used for assisting with clinical differential diagnosis. Future
developments will entail the development and application of more specific
neurochemical ligands and those which bear a closer relationship to the
underlying disease processes, including markers of tau, amyloid and
synuclein pathology.

Publication Types:
    Review
    Review, Tutorial

PMID: 15722899 [PubMed - indexed for MEDLINE]

4: Arch Neurol. 2004 Oct;61(10):1545-50.

Effects of white matter lesions and lacunes on cortical function.

Reed BR, Eberling JL, Mungas D, Weiner M, Kramer JH, Jagust WJ.

University of California Davis Alzheimer's Disease Center, Martinez, CA
94553,USA. brreed@ucdavis.edu

BACKGROUND: Subcortical ischemic vascular dementia has been ascribed to
prominent frontal lobe dysfunction secondary to ischemic lesions in
frontothalamic circuits.Whether small-vessel disease in fact
predominantly affects the frontal lobes is not well documented.
OBJECTIVE: To ivestigate the effects of subcortical lesions (lacunes and
white matter lesions [WML]) on cortical function, as reflected in glucose
metabolism and cognitive function, in elderly individuals. DESIGN:
Cross-sectional analyses of case series. SETTING: Multicenter,
university-based study of subcortical vascular dementia. PATIENTS:
Persons with normal cognition, mild cognitive impairment, or dementia and
with and without lacunes on magnetic resonance images. MAIN OUTCOME
MEASURES: Regional cerebral glucose metabolism, normalized regional
metabolic activity, and neuropsychological test scores. Major hypotheses
were that volume of lacunes and WML correlate selectively with
hypometabolism of prefrontal cortex and failure of executive cognitive
ability. RESULTS:  Lacunes correlated with metabolic rates in
dorsolateral frontal cortex (DLF); WML substantially reduced metabolic
rates throughout cortex, most strongly so in DLF. When regional metabolic
activity was normalized to whole brain activity, lacunes remained
correlated with DLF activity, whereas the WML effect was no longer found,
probably because of its general distribution. Regional cerebral glucose
metabolism and normalized activity in DLF also correlated with cortical
atrophy. Metabolic activity in DLF correlated with executive function,
memory, and global cognitive function, while activity in middle temporal
gyrus correlated with memory and global function but not executive
function. CONCLUSIONS: The metabolic effects of lacunes and WML are most
apparent in DLF, but the effects of WML are generalized and frontal
hypometabolism correlates with memory and global impairment, cognitive as
well as executive function. The effects of subcortical cerebrovascular
disease appear to converge on the frontal lobes but are diffuse, complex,
and of modest magnitude.

Publication Types:
    Multicenter Study

PMID: 15477508 [PubMed - indexed for MEDLINE]

5: Neurology. 2004 Jul 27;63(2):246-53.

White matter lesions impair frontal lobe function regardless of their
location.

Tullberg M, Fletcher E, DeCarli C, Mungas D, Reed BR, Harvey DJ, Weiner
MW, Chui HC, Jagust WJ.

Department of Neurology, School of Medicine, University of California,
Davis, USA. mats.tullberg@neuro.gu.se

OBJECTIVE: To analyze the effect of white matter lesions in different
brain regions on regional cortical glucose metabolism, regional cortical
atrophy, and cognitive function in a sample with a broad range of
cerebrovascular disease and cognitive function. METHODS: Subjects (n =
78) were recruited for a study of subcortical ischemic vascular disease
(SIVD) and Alzheimer disease (AD) contributions to dementia. A new method
was developed to define volumes of interest from high-resolution
three-dimensional T1-weighted MR images. Volumetric measures of MRI
segmented white matter signal hyperintensities (WMH) in five different
brain regions were related to regional PET glucose metabolism (rCMRglc)
in cerebral cortex, MRI measures of regional cortical atrophy, and
neuropsychological assessment of executive and memory function.  RESULTS:
WMH was significantly higher in the prefrontal region compared to the
other brain regions. In all subjects, higher frontal and parietal WMH
were associated with reduced frontal rCMRglc, whereas occipitotemporal
WMH was only marginally associated with frontal rCMRglc. These
associations were stronger and more widely distributed in nondemented
subjects where reduced frontal rCMRglc was correlated with WMH for all
regions measured. In contrast, there was no relationship between WMH in
any brain region and rCMRglc in either parietal or occipitotemporal
regions. WMHs in all brain regions were associated with low executive
scores in nondemented subjects. CONCLUSIONS: The frontal lobes are most
severely affected by SIVD. WMHs are more abundant in the frontal region.
Regardless of where in the brain these WMHs are located, they are
associated with frontal hypometabolism and executive dysfunction.

PMID: 15277616 [PubMed - indexed for MEDLINE]

From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med
Subject: Re: Alzheimer's and CXR
Date: 19 Aug 2005 15:55:36 -0700
Message-ID: <1124492136.184410.107990@f14g2000cwb.googlegroups.com>

David Rind wrote:
> Steve Harris wrote:
> > I've talked about the CT and MRI. One or the other, never both. SPECT
> > is a good test when there's no PET available (it's poor man's PET). But
> > better to put somebody in car or even on a jet, and get the gold
> > standard PET/CT. It's worth every penny.
> >
> > SBH
>
> Why? I agree that PET may do a better job of diagnosing the true
> etiology of dementia (vascular versus AD), but since the management is
> pretty similar, why work so hard (plane flight, expensive test) to find
> out something of relatively minor clinical significance?
>
> (I'm asking this in all seriousness -- my experience is that Dr. Harris
> usually has a good reason for these sorts of recommendations.)


COMMENT:

First because PET/CT will show you a definite organic cause before
SPECT will, and certainly long before standard MRI or CT shows
anything. Thus you can save yourself the MRI and all the workup looking
for secondary causes. If all you have is a separate PET and a CT, you
can still do them both and save yourself the MRI and secondary cause
workup, if positive, and if negative, it can make you look for
secondary causes much more thoroughly.

This has a drastic effect on management. If you KNOW for certain that
your patient has early Alzheimers, you don't have to do a million
dollar workup every time they have a drastic cognitive change from a
UTI or flu or cold or whatever. You now have the guts to treat it and
wait it out without wondering of your patient is dying of meningitis or
stroke or whatever.

Second, it's getting more and more important to make a diagnosis of
cause of early dementia, because there's a lot you can do about the
diseases themselves. Certainly you can treat early vascular dementia
specifically to keep it from progressing, and probably wouldn't want to
do any of *that* (vigorous anti-stroke therapy and probably a statin)
to a patient with pure Alzheimer's.

We're beginning to get a glimmer of treatment option, even for
Alzheimer's disease. High dose vitamin E, fish oil, and
antinflamatories slow it a bit, and in the mouse model curcumin (from
the spice turmeric) actually disrupts AD plaques and stops the disease.
And Indians who eat a lot of turmeric (the main ingredient in curry)
have about quarter the AD incidence we have in the West. Google for a
lot more info. Too early to say if this will hold for humans, but if I
had early AD and knew it from PET, I would certainly be gulping E and
turmeric like crazy. It's benign (unlike antiplatelet therapy, or even
statins in the elderly without vascular risk factors). Surely other
more specific therapies for AD (though I dare say a lot more expensive
than an Indian spice) are just around the corner.

SBH

From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med
Subject: Re: Weight Loss Might Precede Alzheimer's
Date: 27 Sep 2005 21:54:44 -0700
Message-ID: <1127883284.719379.85360@o13g2000cwo.googlegroups.com>

Dan wrote:
> Unexplained weight loss in older people might be an early signal of
> Alzheimer's disease, appearing several years before the memory lapses
> that define the illness, according to an intriguing but unproven new
> theory.
>
> http://debunkbigpharma.blognation.us/blog/_archives/2005/9/27/1263290.html

COMMENT:

Getting a good and complex and varied diet, even in these days of
prepackaged freezer to microwave stuff, takes a certain amount of
high-level cognitive ability.

It is precisely for these reasons that I cringe everytime I see some
epidemiologic study that shows that demented people, or even people
soon-to-become demented, have lower levels of this or that vitamin or
vitamin-influenced gunk. It's very hard to tell which is chicken and
which is egg. In any case, there's no doubt at all that some of the
first signs of dementia (as with depression) are failures in complex
self-care behavior.

As for simple weight loss per se- it's an ominous sign in the elderly
all right, but think occult cancer or depression first before you think
of the "zebra" of early dementia. Also, since women are the "feeders,"
if you see an elderly man losing weight, have a look at the health of
his spouse.

SBH