View unanswered posts | View active topics It is currently Sun Dec 21, 2014 7:20 am



Reply to topic  [ 8 posts ] 
 Rates of cerebral atrophy in LBD, AD/LBD, CBD, PSP, etc 
Author Message

Joined: Fri Aug 11, 2006 1:46 pm
Posts: 4811
Location: SF Bay Area (Northern CA)
Post Rates of cerebral atrophy in LBD, AD/LBD, CBD, PSP, etc
I came across an abstract today on the rates of cerebral atrophy (measured after death) in LBD, AD/LBD, etc. At this time only the abstract is available; the article won't be available for another couple of weeks.

Key points made in the abstract include:

* "The aim of this study was to determine whether rates of brain atrophy differ in neurodegenerative dementias that vary by pathological diagnoses and characteristic protein biochemistry."

* "The largest rates of atrophy were observed in the CBD group... The FTLD-U group showed the next largest rates... (The) Alzheimer's disease, mixed Alzheimer's disease/DLB and PSP groups...all showed similar rates of atrophy... (Atrophy) rates in the DLB group were not significantly different from control rates of atrophy." ("Controls" means healthy brains. FTLD-U means frontotemporal lobar degeneration with ubiquitin-only-immunoreactive changes.)

* "The rates of whole brain atrophy...were significantly increased compared to controls in the Alzheimer's disease, mixed Alzheimer's disease/DLB, FTLD-U, CBD and PSP groups."

* "While rates are unlikely to be useful in differentiating Alzheimer's disease from cases with mixed Alzheimer's disease/DLB pathology, they demonstrate important pathophysiological differences between DLB and those with mixed Alzheimer's disease/DLB and Alzheimer's disease pathology, and between those with CBD and PSP pathology."


Here's the citation and the abstract:

Brain. 2007 Mar 8; [Epub ahead of print]

Rates of cerebral atrophy differ in different degenerative pathologies.

Whitwell JL, Jack CR Jr, Parisi JE, Knopman DS, Boeve BF, Petersen RC, Ferman TJ, Dickson DW, Josephs KA.

Departments of Radiology, Laboratory Medicine and Pathology and Neurology (Behavioral Neurology), Mayo Clinic Rochester, Rochester, MN and Departments of Psychiatry and Psychology Neuroscience (Neuropathology), Mayo Clinic Jacksonville, Jacksonville, FL, USA.

Neurodegenerative disorders are pathologically characterized by the deposition of abnormal proteins in the brain. It is likely that future treatment trials will target the underlying protein biochemistry and it is therefore increasingly important to be able to distinguish between different pathologies during life. The aim of this study was to determine whether rates of brain atrophy differ in neurodegenerative dementias that vary by pathological diagnoses and characteristic protein biochemistry. Fifty-six autopsied subjects were identified with a clinical diagnosis of dementia and two serial head MRI. Subjects were subdivided based on pathological diagnoses into Alzheimer's disease Alzheimer's disease, dementia with Lewy bodies (DLB), mixed Alzheimer's disease/DLB, frontotemporal lobar degeneration with ubiquitin-only-immunoreactive changes (FTLD-U), corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP). Twenty-five controls were matched by age, gender and scan interval, to the study cohort. The boundary-shift integral was used to calculate change over time in whole brain (BBSI) and ventricular volume (VBSI). All BSI results were annualized by adjusting for scan interval. The rates of whole brain atrophy and ventricular expansion were significantly increased compared to controls in the Alzheimer's disease, mixed Alzheimer's disease/DLB, FTLD-U, CBD and PSP groups. However, atrophy rates in the DLB group were not significantly different from control rates of atrophy. The largest rates of atrophy were observed in the CBD group which had a BBSI of 2.3% and VBSI of 16.2%. The CBD group had significantly greater rates of BBSI and VBSI than the DLB, mixed Alzheimer's disease/DLB, Alzheimer's disease and PSP groups, with a similar trend observed when compared to the FTLD-U group. The FTLD-U group showed the next largest rates with a BBSI of 1.7% and VBSI of 9.6% which were both significantly greater than the DLB group. There was no significant difference in the rates of atrophy between the Alzheimer's disease, mixed Alzheimer's disease/DLB and PSP groups, which all showed similar rates of atrophy; BBSI of 1.1, 1.3 and 1.0% and VBSI of 8.3, 7.2 and 10.9%, respectively. Rates of atrophy therefore differ according to the pathological diagnoses and underlying protein biochemistry. While rates are unlikely to be useful in differentiating Alzheimer's disease from cases with mixed Alzheimer's disease/DLB pathology, they demonstrate important pathophysiological differences between DLB and those with mixed Alzheimer's disease/DLB and Alzheimer's disease pathology, and between those with CBD and PSP pathology.

PubMed ID: 17347250


Sat Mar 10, 2007 10:15 pm
Profile

Joined: Fri Feb 16, 2007 6:13 pm
Posts: 102
Location: Fayetteville, AR
Post 
Robin,

You are a wealth of information! The study you cited seems to affirm what I thought I'd read earlier: there is no significant brain atrophy in patients with LBD, as opposed to Alzheimer's/LBD or other. If there were significant atrophy in LBD patients, it would make diagnosis easier, I suppose. As I understand it, in LBD the grey matter doesn't shrink; the problem is with the neurotransmitters. I'm still learning, so I may be mistaken. Thanks for all your information.

Randy


Mon Mar 12, 2007 1:17 am
Profile YIM

Joined: Fri Aug 11, 2006 1:46 pm
Posts: 4811
Location: SF Bay Area (Northern CA)
Post 
Randy,

I find the topic of cell death vs. neurotransmitter problems fascinating, and wish I knew/understood more. I don't think these are mutually exclusive things. In AD (and PSP, which is the disease my father presumably has), there is both brain atrophy and neurotransmitter dysfunction.....I think.

You surmrised that perhaps if there were more atrophy, LBD would be easier to diagnose. I can tell you that for the 2 other diseases mentioned in the article -- CBD and PSP, where atrophy does occur -- diagnosis (and differential diagnosis) is still very difficult. In an '03 study (I might've recently re-posted info on it here??), only 76% of cases where PSP was the clinical diagnosis were diagnosed with PSP upon autopsy. 70% of those misdiagnosed cases were DLBD, CBD, and MSA.

Robin


Mon Mar 12, 2007 7:14 pm
Profile

Joined: Mon Feb 05, 2007 3:43 am
Posts: 215
Location: Seattle, WA
Post 
Generalized atrophy isn't a feature of LBD like it is in AD, but there is specific neuronal loss, most notably in the region where acetylcholine is produced - the best examination of this I've seen was just published in the March issue of _Brain_

The fulltext is free, for the moment, here:
http://brain.oxfordjournals.org/cgi/reprint/130/3/708

This is a *very* chewy document - it took me a very long time to identify all these structures in a model of the brain. Don't operate heavy machinery after reading this. ;0)

*Whitwell JL,
* Weigand SD,
* Shiung MM,
* Boeve BF,
* Ferman TJ,
* Smith GE,
* Knopman DS,
* Petersen RC,
* Benarroch EE,
* Josephs KA,
* Jack CR Jr.

1: Brain. 2007 Mar;130(Pt 3):708-19. Epub 2007 Jan 31.Click here to read

Abstract:
Dementia with Lewy bodies (DLB) is the second most common cause of degenerative dementia after Alzheimer's disease. However, unlike the latter, the patterns of cerebral atrophy associated with DLB have not been well established. The aim of this study was to identify a signature pattern of cerebral atrophy in DLB and to compare it with the pattern found in Alzheimer's disease. Seventy-two patients that fulfilled clinical criteria for probable DLB were age- and gender-matched to 72 patients with probable Alzheimer's disease and 72 controls. Voxel-based morphometry (VBM) was used to assess patterns of grey matter (GM) atrophy in the two patient groups, relative to controls, after correction for multiple comparisons (P < 0.05). Study-specific templates and prior probability maps were used to avoid normalization and segmentation bias. Region-of-interest (ROI) analyses were also performed comparing loss of the midbrain, substantia innominata (SI), temporoparietal cortex and hippocampus between the groups. The DLB group showed very little cortical involvement on VBM with regional GM loss observed primarily in the dorsal midbrain, SI and hypothalamus. In comparison, the Alzheimer's disease group showed a widespread pattern of GM loss involving the temporoparietal association cortices and the medial temporal lobes. The SI and dorsal midbrain were involved in Alzheimer's disease; however, they were not identified as a cluster of loss discrete from uninvolved surrounding areas, as observed in the DLB group. On direct comparison between the two groups, the Alzheimer's disease group showed greater loss in the medial temporal lobe and inferior temporal regions than the DLB group. The ROI analysis showed reduced SI and midbrain GM in both patient groups, with a trend for more reduction of SI GM in Alzheimer's disease than DLB, and more reduction of midbrain in DLB than Alzheimer's disease. Significantly greater loss in the hippocampus and temporo-parietal cortex was observed in the Alzheimer's disease patients when the two patient groups were compared. A pattern of relatively focused atrophy of the midbrain, hypothalamus and SI, with a relative sparing of the hippocampus and temporoparietal cortex is, therefore, suggestive of DLB and this may aid in the differentiation of DLB from Alzheimer's disease. These findings support recent pathological studies showing an ascending pattern of Lewy body progression from brainstem to basal areas of the brain. Damage to this network of structures in DLB may affect a number of different neurotransmitter systems which in turn may contribute to a number of the core clinical features of DLB.

_________________
Cal is not the real name of a real 84 year old with DLB. I don't speak for LBDA, nor do I have clever initials behind my name, so information is provided without warranty. Caveat everybody. I blog at http://PragmaticCaregiver.blogspot.com


Mon Mar 12, 2007 8:06 pm
Profile WWW

Joined: Fri Aug 11, 2006 1:46 pm
Posts: 4811
Location: SF Bay Area (Northern CA)
Post 
I had a hard enough time w/this abstract and didn't make it much further than that a week ago. Other than learning that LBD has "focused atrophy of the midbrain, hypothalamus and SI" (substantia innominata), what I got out of this article was that it is possible to differentiate between LBD and AD on the basis of an MRI.

I thought neurotransmitters were part of neurons *everywhere* in the brain.

Eric - where is acetycoline produced? And do you have any more basic reading to suggest on neurotransmitters? And how about a picture of the brain with its many parts?


Tue Mar 13, 2007 12:49 am
Profile

Joined: Mon Feb 05, 2007 3:43 am
Posts: 215
Location: Seattle, WA
Post 
Oooh, see, that's the juicy part - the substantia innominata is part of the basal forebrain, which is kinda the center of acetylcholine production. People who have brain injuries there, like from a bleed from the anterior communicating artery, get very odd brain symptoms, including confabulation, and they're all caused by this brainwide shortage of acetylcholine. My understanding is that neurons in certain regions "specialize" in their production of various neurotransmitters, and "share" them throughout the brain. This imaging study seems to confirm that portion of my belief. I may be dead wrong.

I've been mostly using Adams and Victor's seminal text, _Principles In Neurology_ - you can get older editions for about $20 used. It's apparently a well-regarded text for neurology education. It's...dry....but readable. I'd *like* a copy of Blumenfeld's _Neuroanatomy Through Clinical Cases_ when the Amazon Fairy swings by. I haven't found a great online resource for this stuff - I find it handiest to have a big hunk of dead tree next to me while I'm looking at stuff online so I can refer as I get confused, which averages about once every 15 seconds.

I swear, a show dog would be a less time-consuming hobby.

Eric

_________________
Cal is not the real name of a real 84 year old with DLB. I don't speak for LBDA, nor do I have clever initials behind my name, so information is provided without warranty. Caveat everybody. I blog at http://PragmaticCaregiver.blogspot.com


Tue Mar 13, 2007 3:45 am
Profile WWW

Joined: Fri Aug 11, 2006 1:46 pm
Posts: 4811
Location: SF Bay Area (Northern CA)
Post 
OK, I finally figured out that the link that Eric posted is to a DIFFERENT article on atrophy; the link is to an article on "Focal Atrophy." I did manage to get a copy of the article on "Rates of cerebral atrophy differ in different degenerative pathologies," and found it more understandable than the "Focal Atrophy" abstract.

Here are a few excerpts that I found most interesting:

"Rates of both whole brain and ventricular change were larger
in the mixed, Alzheimer’s disease, FTLD-U, CBD and PSP
groups compared to controls. There was no significant
difference between the DLB group and the control group in
either measure. The largest rates of atrophy were observed
in the CBD group which had a rate of whole brain atrophy
of 2.3% per year and ventricular expansion of 16% per
year."
("mixed" = DLB/AD mixed pathology)

"The DLB subjects showed a much lower rate of atrophy
compared to the Alzheimer’s disease group, with rates of
whole brain atrophy of only 0.4% per year and ventricular
expansion of only 4.8% per year. ... However, the subjects
with both Alzheimer’s disease and DLB pathology had
larger rates of atrophy which were similar to those
observed in the Alzheimer’s disease group. Therefore, the
presence of the Alzheimer’s disease-type pathological
changes is likely driving the loss of brain volume in these
subjects. ... These rates may help differentiate the mixed
Alzheimer’s disease/DLB cases from the cases with pure
DLB, although will not help to differentiate the mixed cases
from cases with Alzheimer’s disease."

"There was no difference in MMSE or CDR across the
disease groups, although the PSP group had the largest
median MMSE score and lowest CDR, while the CBD group
had the smallest median MMSE score."
(MMSE = Mini-Mental State Examination; CDR = Clinical Dementia Rating scale)

"No correlations were found between rates of whole brain
atrophy or ventricular expansion and disease duration,
baseline MMSE or CDR within any of the disease groups or
across all disease groups."

"There was no difference across the groups in age at
baseline scan, years of education and gender ratios. Within
the disease groups there was also no difference in the time
from disease onset to baseline scan. However, there was a
difference in the time from baseline scan to death. The
mixed group was the furthest from death, while the DLB
group was the closest to death."

"...it is unclear whether it is the combination of b-amyloid
and tau, or only tau that drives the brain loss in Alzheimer’s
disease subjects."
(b-amyloid = beta amyloid)
(My bet is on tau only.)

And here are some LONG excerpts about DLB:

"All 12 patients with a pathological diagnosis of
Alzheimer’s disease also had a clinical diagnosis of
probable Alzheimer’s disease by inclusion
criteria. Similarly all nine cases of DLB had a clinical
diagnosis of probable DLB; none met criteria for Parkinson’s
disease dementia. Nine of the 13 cases with mixed
pathological features of Alzheimer’s disease/DLB had a
clinical diagnosis of Alzheimer’s disease, two had a clinical
diagnosis of DLB and in two cases the diagnosis was
considered to be either Alzheimer’s disease or DLB. Ten of
the 12 FTLD-U cases met criteria for behavioural variant
frontotemporal dementia, while the other two met criteria for
language variant frontotemporal dementia. Of the
pathologically confirmed PSP cases two were given a
clinical diagnosis of apraxia of speech, and one each
behavioural variant frontotemporal dementia, corticobasal
syndrome and probable PSP. The clinical diagnoses in the
five cases of pathologically confirmed CBD were apraxia of
speech, corticobasal syndrome, behavioural variant
frontotemporal dementia, degenerative dementia and
probable PSP."

"These results support previous clinical studies showing that
rates of atrophy are good discriminators of Alzheimer’s
disease from controls, but add extra weight because this is a
pathologically confirmed sample."

"The DLB subjects showed a much lower rate of atrophy
compared to the Alzheimer’s disease group, with rates of
whole brain atrophy of only 0.4% per year and ventricular
expansion of only 4.8% per year. These rates were not
significantly different from the control group suggesting
that very little global brain atrophy occurs over time in this
group and perhaps that the deposition of a-synuclein itself
does not result in widespread neuronal loss. However, the
subjects with both Alzheimer’s disease and DLB pathology
had larger rates of atrophy which were similar to those
observed in the Alzheimer’s disease group. Therefore, the
presence of the Alzheimer’s disease-type pathological
changes is likely driving the loss of brain volume in these
subjects. Similarly, a previous study demonstrated that
atrophy of the temporal lobe correlated with the presence
of Alzheimer’s disease-type pathology in pathologically
confirmed cases of DLB. Although there was a large
degree of overlap between the groups, rates of both whole
brain and ventricular change were substantially larger in the
mixed subjects than those with DLB suggesting that rates
of atrophy may help differentiate these groups of subjects
which are notoriously difficult to differentiate clinically. For
example, a subject presenting with a clinical diagnosis of
DLB with a low rate of atrophy is more likely to show pure
DLB pathology, whereas a subject presenting with a clinical
diagnosis of DLB and a high rate of loss is more likely to
show mixed Alzheimer’s disease/DLB pathology.
Interestingly, of the 13 subjects with mixed Alzheimer’s
disease/DLB pathology the majority had a clinical diagnosis
of Alzheimer’s disease rather than DLB. This suggests that
the memory deficits characteristic of Alzheimer’s disease
are the most likely presentation in cases of mixed
pathology. No previous studies have assessed rates of brain
atrophy on MRI in pathologically confirmed cohorts of
subjects with DLB pathology, although a number of studies
have cross-sectionally assessed subjects with a clinical
diagnosis of DLB and looked at gross atrophy patterns
using post-mortem brains. A number of cross-sectional
studies have found patterns of brain loss similar to those
found in Alzheimer’s disease, although others have
suggested that subjects with DLB show more focused loss
in the basal areas of the brain. Rates of whole brain atrophy
have also been reported to be similar in subjects clinically
diagnosed with DLB and Alzheimer’s disease. The rate
observed in DLB was 1.4% per year which is more similar
to the rate we observed in the mixed pathology group rather
than the pure DLB group, suggesting that the cohorts of
subjects diagnosed with DLB on purely clinical criteria are
likely to contain subjects with mixed Alzheimer’s disease/
DLB pathology."

"While the rates of atrophy appear to differ across
different pathologies, the role of the specific protein
biochemistry is also important. Although most researchers
consider one protein to be the primary protein in each of
the main pathologies, in some cases there are mixed
protein biochemistries. In Alzheimer’s disease, b-amyloid is
considered by many researchers to be the primary protein,
although tau-positive NFT are also present and as
important for the pathological diagnosis. In addition, while
a-synuclein is considered the primary protein in DLB, the
majority of cases also have diffuse b-amyloid-positive
senile plaques, albeit not of the neuritic type required for a
diagnosis of Alzheimer’s disease. These plaques are
considered to be similar to those found in pathological
aging. The fact that our study has shown very low rates of
brain atrophy in the subjects with DLB would suggest that
neither a-synuclein nor b-amyloid causes widespread
neuronal loss, although one study has shown that Lewy
body density correlates with frontal atrophy in cases of
DLB."


Wed Sep 26, 2007 7:03 pm
Profile

Joined: Sat Jan 27, 2007 8:38 pm
Posts: 712
Location: CA
Post 
This explains at least part of the reason for Jerome's misdiagnoses over the early years of his dementia. His GP was ordering annual MRIs of the brain and concluding that nothing was wrong because there was virtually no atrophy. A new tidbit to pass along in our efforts to educate MDs about when to suspect LBD. Thanks for the info, Robin and Randy!

_________________
Renata (and Jerome-in-Heaven)


Thu Sep 27, 2007 5:08 pm
Profile
Display posts from previous:  Sort by  
Reply to topic   [ 8 posts ] 

You cannot post new topics in this forum
You cannot reply to topics in this forum
You cannot edit your posts in this forum
You cannot delete your posts in this forum
You cannot post attachments in this forum

Search for:
Jump to:  
Powered by phpBB © 2000, 2002, 2005, 2007 phpBB Group.
Designed by STSoftware for PTF.
Localized by Maël Soucaze © 2010 phpBB.fr