Joined: Fri Aug 11, 2006 1:46 pm
Location: SF Bay Area (Northern CA)
Using EEG to distinguish DLB and AD
This Italian research was recently published online by the journal Brain. The authors conclude: "If revised consensus criteria for DLB diagnosis are properly applied (i.e. emphasizing the diagnostic weight of fluctuations and REM sleep behaviour disorder), EEG recording may act to support discrimination between AD and DLB at the earliest stages of dementia, since characteristic abnormalities may even precede the appearance of distinctive clinical features." The abstract is copied below.
Brain. 2008 Jan 17 [Epub ahead of print]
EEG comparisons in early Alzheimer's disease, dementia with Lewy bodies and Parkinson's disease with dementia patients with a 2-year follow-up.
Bonanni L, Thomas A, Tiraboschi P, Perfetti B, Varanese S, Onofrj M.
Department of Neurology, Aging Research Center, Ce.S.I., âGabriele d'annunzioâ University Foundation, University G.D'annunzio of Chieti-Pescara, via Fonte Romana, 65124 Pescara, Department of Neurology, Niguarda Caâ Granda Hospital, 20162 Milan and Fondazione Europea Ricerca Biomedica Centro Alzheimer Ospedale Briolini, Gazzaniga (Bergamo), Italy.
EEG abnormalities have been reported for both dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). Although it has been suggested that variations in mean EEG frequency are greater in the former, the existence of meaningful differences remains controversial. No evidence is as yet available for Parkinson's disease with dementia (PDD). The aim of this study was to evaluate whether EEG abnormalities can discriminate between DLB, AD and PDD in the earliest stages of dementia and to do this 50 DLB, 50 AD and 40 PDD patients with slight cognitive impairment at first visit (MMSE >/= 20) were studied.
To improve clinical diagnostic accuracy, special emphasis was placed on identifying cognitive fluctuations and REM-sleep behaviour disorder. EEG variability was assessed by mean frequency analysis and compressed spectral arrays (CSA) in order to detect changes over time from different scalp derivations. Patients' initial diagnoses were revised at a 2-year follow-up visit with neuroimaging evaluation. Initial diagnoses were confirmed in 36 DLB, 40 AD and 35 PDD patients.
The most relevant group differences were observed between the AD and DLB patients in EEGs from posterior derivations (P<0.001). Dominant frequencies were 8.3 +/- 0.6 Hz for the AD group and 7.4 +/- 1.6 Hz for the DLB group, in which most of the patients (88%) exhibited a frequency band of 5.6-7.9 Hz. Dominant frequency variability also differed between the AD (1.1 +/- 0.4 Hz) and DLB groups (1.8 +/- 1.2 Hz, P<0.001). Of note, less than a half (46%) of the patients with PDD exhibited the EEG abnormalities seen in those with DLB.
Graded according to the presence of alpha activity, five different patterns were identified on EEG CSA from posterior derivations. A pattern with dominant alpha bands was observed in patients with AD alone while, in those with DLB and PDD, the degree to which residual alpha and 5.6-7.9 bands appeared was related to the presence and severity of cognitive fluctuations. At follow-up, EEG abnormalities from posterior leads were seen in all subjects with DLB and in three-quarters of those with PDD. Of interest, in four patients initially labelled as having AD, in whom the occurrence of fluctuations and/or REM-sleep behaviour disorder during the 2-year follow-up had made the diagnosis of AD questionable, the initial EEG was characterized by the features observed in the DLB group.
If revised consensus criteria for DLB diagnosis are properly applied (i.e. emphasizing the diagnostic weight of fluctuations and REM sleep behaviour disorder), EEG recording may act to support discrimination between AD and DLB at the earliest stages of dementia, since characteristic abnormalities may even precede the appearance of distinctive clinical features.
PubMed ID#: 18202105 (see pubmed.gov for abstract only)
Joined: Fri Aug 11, 2006 1:46 pm
Location: SF Bay Area (Northern CA)
Thanks to the amazing Patty, I got a copy of this article today.
This is a terrific medical journal article about a standard test (EEG) that could be used to differentiate DLB from AD. One deficiency of the article, curiously not mentioned by the authors, is that none of the diagnoses have been pathologically confirmed. But there seem to be significant differences in those with clinical diagnoses of DLB and AD (and to some extent PDD) such that perhaps the authors don't believe pathological confirmation is required!
Here are some of the more interesting excerpts:
"It is important, however, to differentiate between [AD and DLB] in the earliest stages of dementia because, compared with patients with AD, those with DLB may be considerably more sensitive to adverse effects of neuroleptics and may exhibit faster disease progression and different responses to acetylcholinesterase inhibitors."
"The clinician assessment of fluctuation (CAF)...evaluates fluctuating confusion over a month prior to the clinicianâs interview with an informant. Although fluctuations are also described in patients with vascular dementia and AD, this scale has been reported to have good sensitivity and specificity to DLB... An early seminal study (Walker et al., 2000a) examined characteristics of fluctuations as related to mean QEEG frequency variability across 90 s in DLB, AD and normal control subjects. The greatest variation in mean EEG frequency was noted in the DLB group, where a close relationship was found between EEG variability and CAF scores."
"RBD appeared in 12 more patients initially classified as DLB; in 8 patients severe hypersensitivity to neuroleptic drugs, administered against our suggestions (olanzapine,
risperidone, thiethylparazine), was characterized by rigidity and increment of extrapyramidal symptoms." (Even the researchers couldn't stop antipsychotics from being administered!)
"In none of the AD patients did visual hallucinations or RBD occur during the 2-year follow-up."
"SPECT with ioflupane was normal in all AD patients and abnormal in all DLB patients."
"...It is likely that our findings reflect a patient selection method particularly focused on the presence of fluctuating cognition (as assessed by CAF and ODFA scales) and RBD,
which prominently characterize DLB (Mc Keith et al., 2005). The rarity of both these features in early AD as compared with DLB has only recently been highlighted in the literature."
"...in the earliest stages of dementia, an EEG CSA pattern other than 1 may be regarded as a reliable negative predictor of a diagnosis of AD even when clinical features of dementing diseases other than AD and deemed typical of DLB have not yet appeared."
"...in conclusion our study shows methods of analysis and quantitative comparisons supporting the suggestion that EEG might be helpful in the diagnosis of DLB."
Here are extensive excerpts from this article:
"Dementia with Lewy bodies (DLB) has been reported to be
the second most common neurological cause of dementia
after Alzheimerâs disease (AD). Clinically, fluctuations in
attention, visual hallucinations and extrapyramidal signs
(including bradykinesia and rigidity, but not resting tremor)
have been indicated as cardinal features of DLB (McKeith
et al., 1996). However, while neuropathologic series have
demonstrated high accuracy for the clinical diagnosis of AD,
the accuracy of the clinical diagnosis of DLB has been less
satisfactory because, some of the âcoreâ clinical features of
DLB may not invariably appear even during the entire course
of disease or may overlap to some extent with AD. As a
result, DLB tends to be underdiagnosed during life and mostly
misdiagnosed as AD. It is important, however, to differentiate
between these diseases in the earliest stages of dementia
because, compared with patients with AD, those with DLB
may be considerably more sensitive to adverse effects of
neuroleptics and may exhibit faster disease progression
and different responses to acetylcholinesterase inhibitors.
In light of the limitations on the level of accuracy that can
be achieved by making a diagnosis of DLB only on the
grounds of clinical history and examination, great emphasis
has recently been placed on methods evaluating the uptake
of either dopamine transporter (DAT) in basal ganglia
or metaiodobenzylguanidine (MIBG) in the myocardium.
These methods, respectively exploring the integrity of
the nigrostriatal dopaminergic system and of postganglionic
sympathetic cardiac innervation, have been suggested to
improve clinical diagnostic accuracy of DLB, but there is a
clear need of other markers to assist with accurate identifi-
cation of this entity during life." ...
"Several electroencephalographic studies on dementia
were performed in the years preceding the identification of
DLB as a widespread dementing disorder. Correlations
between electroencephalographic spectral measures and
severity of cognitive impairment were reported by some
authors, but not by others... In the latest revision of clinical
diagnostic criteria for DLB (Mc Keith et al., 2005), prominent
slow wave activity on EEG with temporal lobe transient
sharp waves was regarded as a supportive feature for its
diagnosis. However, this statement is largely based on
anecdotal reports, since only two studies showed statistical
differences between quantitative EEG (QEEG) recordings of
DLB and AD patients, while in three studies no significant
group differences were found. It is not unlikely, however, that
different EEG quantification methods or clinical assessments
insufficiently focused on more recent DLB diagnostic core or
supportive criteria may have contributed to failures."
"Since their first formulation, consortium clinical diagnostic
criteria for DLB (McKeith et al., 1996; Mc Keith et al., 2005)
have been based on a set of core and supportive features.
Among those now regarded as highly suggestive of DLB is
REM Sleep Behaviour Disorder (RBD), whose specificity to
synucleinopathies has been highlighted in several papers.
Conversely, cognitive fluctuations (described as disorders of
consciousness, ranging from reduced arousal to stupor) have
long been considered central to DLB identification (McKeith
et al., 1996), but structured methods for their detection have
been proposed only recently (Walker et al., 2000b). The
clinician assessment of fluctuation (CAF), for example,
evaluates fluctuating confusion over a month prior to the
clinicianâs interview with an informant. Although fluctuations
are also described in patients with vascular dementia and
AD, this scale has been reported to have good sensitivity
and specificity to DLB, revealing not only quantitative
(frequency and severity), but also qualitative differences
between this and other dementing disorders. An early
seminal study (Walker et al., 2000a) examined character-
istics of fluctuations as related to mean QEEG frequency
variability across 90 s in DLB, AD and normal control
subjects. The greatest variation in mean EEG frequency
was noted in the DLB group, where a close relationship
was found between EEG variability and CAF scores. An
important implication of these findings is that clinicians
might reliably capture weekly or monthly changes in
attention and vigilance by simply analysing EEG
recordings of just a few seconds. In fact, a DLB patient
with the maximal CAF score, indicating particularly severe
fluctuations over the month before the interview, was shown
to have a particularly unstable, second-to-second fluctuating
rhythm of activation during the whole 90 s period. Whether
DLB patients with less severe fluctuating cognition display
such a distinctive EEG pattern has not been equally
clear, however." ...
"The aim of the present study was to investigate whether
EEG abnormalities in patients with clinically diagnosed AD,
DLB, or PDD had distinctive characteristics from the
earliest stages of deterioration (primary endpoint). To
explore this, analyses were based on EEG recordings at
first referral to our tertiary clinic, provided that the interval
between the first visit and estimated onset of dementia
did not exceed 1 year and global cognitive impairment
was relatively mild (Mini-Mental-State-Examination). CAF
scales and RBD assessments were used among other
supportive elements for diagnosis. EEGs were analysed
with the same methods used in previous controversial
literature and with methods focused on EEG variability
assessment over time, such as mean frequency, mean
frequency variability (MFV) ...and compressed spectral
arrays (CSA), by which even changes in single EEG
derivations can be detected."
"The second endpoint of this study was to evaluate
whether EEG differences are merely statistical or might
express cut-off levels dependent on methods of evaluation.
The third endpoint was to understand whether PDD
patients present with EEGs similar to those recorded in
DLB or early AD patients and therefore to investigate
whether DLB and PDD are overlapping entities."
"Differentiating patients with DLB from those with AD
can be extremely challenging, especially in early-stage
dementia because, in this phase, the full spectrum of
clinical features supporting a diagnosis of DLB may yet be
expressed incompletely. For this reason, after enrollment in
the study, each patient was prospectively followed up for at
least 2 years, during which the appropriateness of initial
diagnostic categorization was carefully re-evaluated."
"Concordant with their match on initial MMSE, DLB, PD
and AD patients exhibited no differences at presentation
on other global test of cognition. However, frontal dys-
function (as assessed by FAB) was greater in DLB than
AD patients. DLB patients also had, on average, the
highest initial neuropsychiatric inventory score, indicating
increased frequency and/or severity of behavioural
disturbances at presentation (DLB > PDD > AD).
Conversely, severity of parkinsonism (as assessed
by the UPDRS-motor subsection) was greatest in the
PDD group (PDD > DLB > AD)."
"Fluctuations (as assessed by CAF) were reported for
all of the DLB patients and almost a half of the PDD
patients, but for none of the AD patients. ... Consistent
with the results obtained using CAF, there also were
significant group differences using ODFA [One-Day Fluc-
tuation Assessment], with patients with DLB having, on
average, the highest score and approximately one-third
of those with PDD with a score in the same range as
that of DLB patients. As expected, within the PDD
group, there were significant differences in ODFA
between PDD-F and PDD-NF."
"Even though 34 of the 36 DLB patients presented with
some signs of parkinsonism, only 19 patients scored
at least 2 on items 22, 28, 29 or 31 of UPDRS III
motor subscale (rigidity, posture, gait, bradykinesia).
None of the AD patients had resting tremor or rigidity
score above 1 as assessed with UPDRS III motor sub-
scale items 22â26. None of the AD patients scored >0
a items 27, 28, 29, 31."
"26 (72%) DLB patients complained of at least one
episode of visual hallucinations. In 12 (33.3%) patients
these were reported as recurrent. Six of them also
presented psychotic episodes. 28 PDD patients
suffered from recurrent complex visual hallucinations
and 3 PDD patients from delusions. RBD was docu-
mented in 14 (40%) of the PDD patients. Conversely,
none of the AD patients had visual hallucinations or
RBD at presentation, even though sleep disorders
not including nightmares were present in 6 (15%)." ...
Classic interpretation methods (CIM)
...In particular, significant differences were observed in
the posterior derivations, with all of the AD subjects
exclusively exhibiting an alpha rhythm and almost two-
thirds of the DLB and one-third of the PDD displaying a
theta/delta rhythm." ...
RBD appeared in 12 more patients initially classified as
DLB; in 8 patients severe hypersensitivity to neuroleptic
drugs, administered against our suggestions (olanzapine,
risperidone, thiethylparazine), was characterized by rigidity
and increment of extrapyramidal symptoms. Twelve more
patients experienced recurrent visual hallucinations and
16 patients reported episodes of delirium. None of these
symptoms occurred in any AD patient. RBD appeared in
8 more and visual hallucinations in 4 more PDD patients.
Delusional ideation appeared in 14 DLB patients and in
5 AD patients. In DLB patients, the CAF score increased
by 2.2 +/- 2.0 and in 12 of them, axial dystonia with
camptocormia (7 patients) or lateral axial dystonia (5
patients) appeared. Consistent with the initial diagnosis
of DLB, both UPDRS score and H/Y stage also increased."
[Robin's note: olanzapine = Zyprexa; risperidone = Risperdal; if they mean thiethylperazine, this is Torecan....never heard of this]
[From a journal article: Camptocormia is defined as an abnormal flexion of the trunk that appears when standing or walking and disappears in the supine position.]
"In PDD patients, the CAF score increased and in 10
PDD-NF patients who scored 0 at the onset, CAF scores
rose (range 2â8). In the AD group selected for the study,
CAF score did not change. In none of the AD patients did
visual hallucinations or RBD occur during the 2-year
follow-up. SPECT with ioflupane was normal in all AD
patients and abnormal in all DLB patients."
"The different EEG variables analysed in our study showed
some distinct and specific patterns in patients affected by
DLB or PDD-F. When EEGs were interpreted with the
classic visual inspection methods, an alpha rhythm in
posterior derivations was observed in all of the patients
with AD, but only in approximately two-thirds of those
with DLB. In the PDD group, an alpha rhythm was
observed in almost three-quarters of the patients." ...
"Our first relevant finding was the identification of slow
activities (5.6â7.9 Hz) in posterior derivations of all DLB
patients, which significantly differentiated these patients
from those with AD. This activity was defined pre-alpha
because it was suppressed by eye opening. Two prior
studies, quantifying EEG characteristics during poly-
somnography in patients with RBD and DLB/PDD
compared with normal controls, had shown differences
between these two groups in the same EEG frequency
band. Our study highlights differences between patients
with DLB/PDD and those with AD. The variability of EEG
dominant and mean frequency activity was our second
most relevant finding leading to the identification of specific
EEG patterns in DLB or PDD-F. Confirming earlier
suggestions from a previous study, MFV correctly cate-
gorized 90% of AD patients and 75% of DLB patients. The
variability of the EEG frequencies in relaxed waking
conditions emerged however more clearly by using
the CSA method of representation that, previously, had
only been used to assess coma, anaesthesia levels and
background EEG activity of epileptogenic zones. Showing
that dominant frequencies (DF) in DLB were either in the
pre-alpha band or varied across time with pseudocyclic
patterns of delta-theta/pre-alpha or theta-prealpha/alpha,
this method was particularly useful in differentiating
DLB from AD patients, as well as PDD patients with
cognitive fluctuations (PDD-F) from those without
"...Therefore, these EEG abnormalities, when observed in a
patient with initial signs of cognitive decline, i.e. MMSE >=
20, are highly suggestive of a diagnosis of DLB."
"When EEGs were recorded 2 years later, further
alterations were observed which differentiated groups of
patients, even though the administration of drugs not
allowed at baseline could have partly marred the results.
In DLB patients and in 74.3% of PDD patients EEGs were
similar, with a stable pre-alpha activity or unstable DF over
time, with variability above 3 Hz, consisting of the presence
of unstable alpha, pre-alpha, theta and delta activities.
In 72.5% of AD patients and in 25.7% of PDD patients
(all PDD patients without cognitive fluctuations) DFV was
below 3 Hz and alpha activity was present." ...
"Analyses focused on the third endpoint showed that PDD
in its early course can apparently be separated into two
groups: one with fluctuating cognition elements and EEG
pattern abnormalities similar to those observed in early
DLB and a group with EEGs similar to that of AD patients
and without fluctuating cognition."
"With follow-up, however, the majority of PDD patients
(74.3%) had increased CAF scores and displayed the same
EEG abnormalities characterizing those with DLB. The
presence of two different clusters in early PDD suggests a
variable distribution of neuropathological abnormalities in
different patients, cumulating however across time to show,
at follow-up, clinical and EEG patterns similar to those
observed in DLB."
"...It is likely that our findings reflect a patient selection
method particularly focused on the presence of fluctuating
cognition (as assessed by CAF and ODFA scales) and RBD,
which prominently characterize DLB (Mc Keith et al., 2005).
The rarity of both these features in early AD as compared with
DLB has only recently been highlighted in the literature.
It might be, therefore, that the greater EEG abnormalities
observed by others in less recent âAD seriesâ depend in part
on heterogeneity of patient populations and, in particular, may
reflect the inclusion of a variable number of DLB cases mis-
diagnosed as having AD. In support of this interpretation is the
observation that, in the most recent literature, EEG alterations
reported for AD patients were modest and consistent
with those shown in our study. Therefore, by emphasizing
the diagnostic weight of cognitive fluctuations, RBD and
SPECT abnormalities, we were able to observe specific EEG
abnormalities, that accurately distinguished DLB from AD
patients. In fact, in the present study, all of the patients
clinically diagnosed at presentation as having DLB had a
positive CAF score and, in most of them, this score
increased during the 2-year follow-up period despite the
administration of cholinesterase inhibitors (allowed only
after baseline examination). Conversely, in the AD group,
none of the patients had a positive CAF score at
presentation and the few in whom the CAF score became
positive at follow-up (10%) were excluded from primary
"In the DLB group, RBD was observed in 61% of the
patients at admission and 94% of the patients at follow-up.
In the AD group, none of the patients had RBD at admis-
sion, although few developed RBD at follow-up. Altogether,
of the 50 patients clinically diagnosed as having AD at
presentation, the 10 who developed RBD, parkinsonism,
cognitive fluctuations, or visual hallucinations during the
2-year follow-up period were excluded from main analysis
because their initial diagnosis was felt to have become
questionable. Of interest, initial EEG abnormalities corres-
ponding to patterns 2 and 3 were observed in seven
of these patients, suggesting that, in the earliest stages of
dementia, an EEG CSA pattern other than 1 may be
regarded as a reliable negative predictor of a diagnosis of
AD even when clinical features of dementing diseases other
than AD and deemed typical of DLB have not yet appeared."
"We would also highlight that, based on consensus
criteria for the diagnosis of DLB (McKeith et al., 1996),
the frequency of core features in our patient population
was higher than that usually reported in the literature.
A possible explanation is that our patient population was
prospectively followed, and thereby strictly evaluated for the
presence of distinctive features of DLB, especially because
our patients were enrolled beginning from 2001, when
5 years had passed since the scientific world started posing
a special emphasis on investigating the presence of these
"Even though a putative pre-mortem diagnosis of dementia
subtypes might be extremely difficult, in conclusion our study
shows methods of analysis and quantitative comparisons
supporting the suggestion that EEG might be helpful in the
diagnosis of DLB (Mc Keith et al., 2005)."