REVIEW

A REVIEW OF COGNITIVE IMPAIRMENTS IN DEMENTIA

WITH LEWY BODIES RELATIVE TO ALZHEIMER’S DISEASE
AND PARKINSON’S DISEASE WITH DEMENTIA
Claudia Metzler-Baddeley
(The Research Institute for the Care of the Elderly, St. Martin’s Hospital, Bath, UK)

ABSTRACT

Dementia with Lewy bodies (DLB) has recently been identified as a separate disease but diagnosis can be difficult, in
particular the differentiation from related dementias of Alzheimer’s disease (AD) and Parkinson’s disease with dementia
(PDD). Careful cognitive assessment may aid differential diagnosis between these different types of dementia and can
provide theoretical insight into the nature of the underlying impairments. Recent reviews on DLB have primarily dealt with
medical issues of clinical diagnostic criteria, pathology, epidemiology and treatment (Ballard, 2004; Barber et al., 2001;
Cercy and Bylsma, 1997; Cummings, 2004; Kaufer, 2004; McKeith, 2002; McKeith et al., 2004a; Rampello et al., 2004)
and only a few papers have reviewed cognitive impairments in DLB (Collerton et al., 2003; Lambon-Ralph et al., 2001;
Simard et al., 2000). The present paper is more specifically targeted to a neuropsychological audience. It provides an up-
to-date, detailed and comprehensive review of the available evidence regarding visual and olfactory perception, attention,
cognitive fluctuation, frontal-executive functions, working memory, episodic memory, and semantic memory in DLB
relative to AD and PDD. In addition, an attempt is made to relate available data to current theoretical frameworks of
cognition. Implications for future research and clinical issues such as the problem of differential diagnosis, and the relation
between cognitive impairments and clinical features of visual hallucinations and cognitive fluctuation will be discussed.

Key words: Lewy body disease, Alzheimer’s disease, perception, attention-executive function, memory

INTRODUCTION observed in other dementias too. The clinical

Dementia with Lewy bodies (DLB) (Cummings,
2004; McKeith et al., 1996) has recently been
recognised as a separate disease (McKeith et al.,
1996; for review see also Ballard, 2004; Barber et
al., 2001; Cercy and Bylsma, 1997; McKeith et al.,
2004a). Pathologically, DLB is characterised by the
formation of abnormal protein inclusions called
Lewy bodies (LBs) in the cerebral cortex, in brain
stem nuclei and parts of the basal forebrain
cholinergic system. The three core clinical
diagnostic features of DLB are: cognitive
fluctuation, i.e. marked variations in attention and
alertness which may occur over periods that range
from minutes to weeks; mild and spontaneous
Parkinsonism, typically bradykinesia and rigidity;
and visual hallucinations, such as imagining seeing
a family member or pet (Cummings, 2004;
McKeith et al., 1996). Supporting diagnostic
features for DLB include sensitivity to neuroleptic
drugs, frequent falls, and rapid eye movement sleep
behaviour disorders (RBD) (Cummings, 2004;
McKeith et al., 1996).
Clinical diagnosis of DLB can be difficult
because of the variability and the overlap of
symptoms between DLB and other related
dementias, notably Alzheimer’s disease (AD) and
Parkinson disease with dementia (PDD). It is also
the case that all of the symptoms associated with
DLB are not specific to the disease but may be
manifestation of DLB and AD for instance can be
very similar (for neuropathological features see
Ballard et al., 2004; Harrington et al., 1994;
McKeith et al., 1996; Merdes et al., 2003; Lippa
and McKeith, 2003). In both conditions, patients
may initially present with progressive cognitive
decline without any other neurological
abnormalities. Memory impairments are frequently,
but in DLB not necessarily, the earliest and most
prominent feature. With time, cognitive deficits
become more widespread and patients progress to
severe dementia (Salmon et al., 1996).
Recent clinico-pathological evidence (e.g.,
Aarsland et al., 2004; Ballard et al., 2002;
Colosimo et al., 2003; Horimoto et al., 2003;
McKeith and Mosimann, 2004; Tsuboi and
Dickson, 2005) also indicates that DLB and PDD
may reflect diseases of the same underlying LB
spectrum. The majority of PDD patients exhibit the
core clinical diagnostic features of DLB (McKeith
and Mosimann, 2004) and there are few or no
pathological differences between DLB and PDD
(Tsuboi and Dickson, 2005). It has been suggested
that the two diseases only differ in the chronology
of symptom progression, i.e. in DLB, dementia
develops before Parkinsonism and in PDD,
Parkinsonism develops before dementia
(Cummings, 2003, 2004; Horimoto et al., 2003;
Tsuboi and Dickson, 2005). Current reviews also
acknowledge the close link between DLB and

Cortex, (2007) 43, 583-600

584 Claudia Metzler-Baddeley
another LB related disease, RBD (Boeve et al.,
1998, 2004; Ferman et al., 1999, 2002; Petit et al.,
2004), and recommend the inclusion of RBD as
supporting feature (Cummings, 2004).
DLB diagnosis tends to have high specificity
but sensitivity varies and was reported to be very
low in some studies (McKeith et al., 2004a). That
means, cases that are clinically diagnosed as DLB
are usually pathologically confirmed, whereas some
pathologically post-mortem diagnosed cases were
missed clinically and were often misdiagnosed as
AD. One of the reasons for misdiagnosis of DLB is
the difficulty to characterise and measure the core
diagnostic features of visual hallucinations and
cognitive fluctuations with the latter proving to be
the most difficult to capture (Ballard, 2004).
Early and accurate diagnosis of DLB, however,
is imperative to optimize treatment and care for
these patients. There is preliminary evidence from
only one placebo-controlled trial (McKeith et al.,
2000b) and a few studies based on small patient
numbers (Holm, 2004; Lebert et al., 1998; Samuel
et al., 2000; Wilcock and Scott, 1994) that
cholinesterase inhibiting (ChEI) medication has
beneficial effects on attention and disturbances of
consciousness in DLB. Patients with DLB are
known to develop marked cholinergic depletion
(Perry et al., 1994; Samuel et al., 1997) and may
therefore especially benefit from this class of drugs
(McKeith et al., 2000b). On the other hand, DLB
patients can exhibit life-threatening adverse effects
and exacerbations of parkinsonian symptoms in
response to typical and atypical antipsychotic
drugs, which may be prescribed for the treatment
of hallucinations and delusions or agitation in AD.
Misdiagnosis of DLB as AD is therefore potentially
extremely dangerous for these patients. In addition,
drugs prescribed for the parkinsonian motor
impairments in DLB might exacerbate psychotic
symptoms such as visual hallucinations.
Furthermore, although there is broad agreement on
the existence and general symptoms found in DLB,
the evidence is not yet sufficient to be accepted by
the U.S. Food and Drugs Administration as a
separate diagnosis. This situation makes it difficult
to develop and evaluate specific drug treatments
and psychological interventions for DLB patients.
Thus, to ensure that DLB patients have access
to appropriate treatment and interventions in the
future, it is important to extend our current
knowledge about the disease. Understanding the
nature of cognitive impairments in DLB is thereby
important for several reasons. Identifying
similarities and differences between DLB and AD
as well as DLB and PDD, is the first step in
developing tests that are differentially sensitive to
the different conditions, thus providing suitable
screening tests to aid clinical diagnosis.
Understanding the quality of impairments also
provides valuable information for patients and
carers, helping them to develop better coping and
care strategies. Furthermore, comparing the profile
of cognitive impairment between patient groups
allows the investigation of theoretical questions
about the normal organisation of cognitive
functions. For instance, patients with AD
demonstrate disproportional impairments in some
attentional components such as selective attention
but not in others such as sustained attention,
suggesting that central executive functions can be
fractionated (Baddeley et al., 2001; Perry and
Hodges, 1999). This raises the question of whether
patients with DLB also exhibit disproportionate
impairments, which might have implications for
understanding the process underlying executive
control (Baddeley, 1992).
In contrast to the majority of other recent
review papers on DLB (Ballard, 2004; Barber et
al., 2001; Cercy and Bylsma, 1997; Cummings,
2004; Kaufer, 2004; McKeith, 2002; McKeith et
al., 2004a; Rampello et al., 2004), the present
paper will therefore focus on the
neuropsychological deficits associated with DLB.
There are only a few earlier review papers that
have focused on cognitive impairments in DLB.
Collerton et al. (2003) carried out a meta-analysis
on studies published until May 2002, and Lambon-
Ralph et al. (2001) and Simard et al. (2000) have
published earlier qualitative reviews. The present
paper provides an up-to-date and systematic review
of current evidence on impairments in perception,
attention, executive function and memory. The
review is based primarily on studies that have not
been included in previous qualitative reviews and
aims to provide a basis to identify areas which
require further investigation in the future. Given
the clinical and theoretical significance of
understanding the neuropsychology of DLB and
related diseases, the review will focus on studies
that have compared cognitive functions in DLB
with those in AD and/or PDD.
Studies included in the present review have
been identified in the electronic databases PubMed
and PsychINFO and in the reference sections of
other review papers. The present review focuses on
studies that have been published in English from
2000 onward since earlier work has been reviewed
before (see Collerton et al., 2003; Lambon-Ralph et
al., 2001; Simard et al., 2000). The final search for
this review was carried out in May 2005. The
keywords used for searching were dementia with
Lewy bodies combined with each of the following
terms: cognition, attention, executive function,
frontal, perception, construction, visual, auditory,
olfactory, tactile, hallucinations, cognitive
fluctuations, memory, working memory, episodic
memory, semantic memory, procedural memory,
explicit memory, implicit memory, priming, motor
skills, Alzheimer’s disease, and Parkinson’s disease
with dementia. These searches together generated a
total number of 1,457 articles. Out of these, only
studies that reported data on performance in
 Cognitive deficits in Lewy body dementia
cognitive tasks by a group of patients with DLB
compared to at least one other group of patients
with dementia, such as patients with AD, patients
with PDD, or another subgroup of DLB patients,
were included. In addition, patients also had to be
diagnosed according to accepted consensus
guidelines for clinical and/or pathological diagnosis
and had to be matched minimally on variables of
age and cognitive impairment. Table I summarises
some relevant methodological features of the
studies that were selected as basis to review
cognitive impairments. Any studies that did not
involve cognitive testing or did not fulfil any of the
other selection criteria, such as studies or reviews
on clinical issues of epidemiology, diagnosis,
pathology, physiology, treatment, medication,
imaging and single-cases were not included in
Table I (total number discarded: 1,367). However,
such studies, if relevant, are mentioned in sections
discussing possible underlying impairments of
cognitive deficits.
COGNITIVE IMPAIRMENTS IN DEMENTIA
WITH LEWY BODIES
Most studies that have investigated cognitive
impairments in DLB have primarily used standard
neuropsychological tests to outline DLB patients’
cognitive profile. The overall pattern emerging
indicates that DLB patients tend to develop earlier
and more severe visuoperceptual, attentional and
frontal-executive impairments than AD patients,
whereas AD patients tend to be earlier and more
impaired in memory tasks (Collerton et al., 2003;
Dalrymple-Alford, 2001; Noe et al., 2004). Patients
with DLB and PDD tend to show a similar
neuropsychological pattern (Aarsland et al., 2003;
Noe et al., 2004).
PERCEPTION
The study of perception encompasses
investigation of sensory processes i.e. the simple
conscious experience associated with physical
aspects of a stimulus such as brightness, loudness
etc. (sensation), as well as the conscious experience
of objects and object relationships (perception) i.e.
how we form a conscious representation of the
outside world. Work on perceptual functions in
DLB has been almost exclusively carried out in the
visual domain, although there are a few studies that
have investigated olfactory functions. For an
overview of studies of perception see Table II.
Visual Perception and Visual Construction
Earlier studies, comparing DLB and AD
patients, used relatively complex subtests from
standard neuropsychological tests such as Wechsler
585
Adult Intelligence Scale (WAIS-R) or the
Cambridge Cognitive Examination (CAMCOG)
(see Collerton et al., 2003; Lambon-Ralph, 2001;
Simard et al., 2000). Most of these studies found
DLB patients equally or more impaired than AD
patients.
Studies that have looked at DLB and AD
patients’ copying performance in tasks such as
clock, cube, or cross copying or the Pentagon
copying subtest of the Mini Mental State
Examination (MMSE) (Ala et al., 2001, 2002;
Cahn-Weiner et al., 2003; Cormack et al., 2004a;
Noe et al., 2004; for earlier studies see Collerton et
al., 2003; Lambon-Ralph et al., 2001; Simard et al.,
2000) found DLB patients usually more impaired
in copying, whereas both groups tend to be equally
impaired in drawing from memory. This pattern
indicates a primary memory problem in AD and a
primary visual-perceptual problem in DLB.
Consistent with this interpretation, Cormack et
al. (2004a) reported that in DLB patients, deficits
in copying of the MMSE Pentagon figure was only
linked to deficits in perception and praxia whereas
in AD patients, deficits were linked to more global
cognitive impairment. Cormack et al. (2004a) also
included PDD patients in their study and found a
similar pattern for DLB and PDD with both groups
performing significantly worse than the AD
patients. Similarly, Noe et al. (2004) reported equal
impairments in DLB and PDD patients in matching
of the Benton Visual Retention task and on the
Rosen Drawing Test, whereas AD patients
performed significantly better. Cahn-Weiner et al.
(2003) did not detect a difference between DLB,
AD, and PD patients with cognitive impairment in
overall clock drawing performance but reported
DLB patients to produce more conceptual errors
than AD and PD patients. DLB and PD patients
also made more planning errors than patients with
AD.
In a recent study by Mosimann et al. (2004),
DLB, PDD, and AD patients as well as matched
healthy controls were compared in visual
discrimination tasks (length, size, angle), object
and form perception tasks, and space motion tasks
(dot position, motion perception, visual counting).
DLB and PDD patients were more impaired in all
tasks than the AD patients and performed worse on
object perception than space motion perception.
These results are consistent with previous studies
that have used the Visual Object and Space
Perception Test (VOSP) and found DLB patients to
be impaired in object and space perception
including early perception as assessed with
fragmented letters, whereas AD patients performed
normally (Calderon et al., 2001; Lambon-Ralph et
al., 2001).
Finally, Cormack et al. (2004b), tested DLB
and AD patients in a visual search task under a
parallel search condition measuring automatic
visual search (pop-out effect) and a serial search
586 Claudia Metzler-Baddeley

TABLE I
Methodological features of studies included in review

Mean age of Mean MMSE N of DLB N of DLB Other Matching N of DLB Neuroimaging/EEG/other
DLB patients (or other) of patients patients ChE groups of dementia diagnoses correlates
DLB patients medicated groups for pathology
confirmed
Author (year)
Aarsland et 73 (mild) 24 (mild) 60 (9 mild, n/a AD cog. imp. yes no
al. (2003) 74 (severe) 18 (severe) 51 severe) PDD adjusted for
PSP age and
education
Ala et al. 75 22 17 n/a AD age, yes no
(2001, 2002) education,
cog. imp.
Ballard et al. 79 18 15 no AD age, sex, no no
(2001) NC cog. imp.
Ballard et al. 77 16 50 n/a AD age, cog. no no
(2002) PDD imp.
PD
NC
Cahn-Weiner 74 112 (DRS) 20 2 AD age, no no
et al. (2003) PDD education,
cog. imp.
Calderon et 73 20 10 n/a AD age, no no
al. (2001) NC education,
cog. imp.
Cormack et 78 17 50 n/a AD age, cog. no no
al. (2004a) PDD imp.
PD
Cormack et n/a 57 (CAMCOG) 20 no AD age, cog. no no
al. (2004b) PD imp.
NC
Doubleday 68 15 41 n/a AD age, sex, 4 SPECT
et al. (2002) education,
cog. imp.,
duration
Gilbert et al. 76 23 12 n/a AD age, sex, yes no
(2004) NC education,
cog. imp.
Hamilton et 74 23 24 n/a AD age, yes no
al. (2004) NC education,
cog. imp.
Lambon-Ralph 76 19 10 n/a AD age, cog. no no
et al. (2001) NC imp.
McKeith 74 17 71 35 DLB non- age, cog. no no
et al. (2004b) (hallucinators) hallucinators imp.
McShane et 76 15 65 n/a AD age, cog. yes no
al. (2001) NC imp.
Mori et al. 74 19 24 n/a AD age, sex, no MRI for diagnosis
(2000) education,
cog. imp.
Mosimann et 78 19 20 12 AD age, sex, no no
al. (2004) PDD education,
PD cog. imp.
NC
Noe et al. 73 36 (m-MMSE) 16 2 AD age, cog. 1 CT, MRI for diagnosis
(2004) PDD imp.,
duration
Perriol et al. 71 122 (DRS) 10 6 AD age, no EEG
(2005) PDD education,
NC cog. imp.
Simard et al. 77 100 (DRS) 14 n/a AD age, no no
(2002) NC education,
duration,
cog. imp.
Simard et al. 74 105 (DRS) 8 n/a AD age, no no
(2003) education.
cog. imp.
Walker et al. n/a n/a 37 n/a AD age, sex, no EEG
(2000b) VD cog. imp.
NC
Westervelt et 77 23 9 n/a AD age, sex, no no
al. (2003) cog. imp.
Note. PSP = progressive supranuclear palsy; NC = normal controls; VD = vascular dementia; cog. imp. = cognitive impairment; CT = computer tomography;
EEG = electroencephalogram; SPECT = single photon emission computed tomography.
 Cognitive deficits in Lewy body dementia 587

TABLE II
Overview of neuropsychological findings for perception

Ala et al. Cahn- Calderon Cormack Cormack Lambon- McShane Mosimann Mori Noe Simard Westervelt
(2001, Weiner et et al. et al. et al. Ralph et et al. et al. et al. et al. et al. et al.
2002) al. (2003) (2001) (2004a) (2004b) al. (2001) (2001) (2004) (2000) (2004) (2003) (2003)
Visual perception
MMSE: Pentagon DLB < – – DLB = PDD – – – – – – – –
copying AD < AD < PD
Clock drawing – DLB = – – – – – – – – – –
AD = PD
Rosen drawing test – – – – – – – – – DLB = – –
PDD <
AD
Parallel search – – – – DLB < AD – – – – – – –
= PD
Visual – – – – – – – DLB = PDD – – – –
discrimination < AD
(length, size, angle)
Space-motion – – – – – – – DLB = PDD – – – –
(motion, visual < AD
counting)
Object-form - – – – – – – – DLB = PDD – – – –
perception < AD
VOSP: cubes – – DLB < AD – – – – – – – – –
= NC
VOSP: letters – – DLB < AD – – DLB < AD – – – – – –
= NC = NC
VOSP: object – – DLB < AD – – DLB = AD – – – – – –
decision = NC = NC
VOSP: shape – – DLB = AD – – DLB < AD – – – – – –
detection = NC = NC
VOSP: silhouettes – – DLB = AD – – – – – – – – –
< NC
Object size – – – – – – – – DLB < – – –
discrimination AD
Form – – – – – – – – DLB < – – –
discrimination AD
Overlapping – – – – – – – – DLB < – – –
figures AD
Visual counting – – – – – – – – DLB < – – –
AD
Benton Judgement – – – – – – – – – – DLB < –
Line Orientation AD
Benton Visual – – – – – – – – – DLB = – –
Retention Task PDD <
(matching) AD

Olfactory perception
Identification – – – – – – DLB < AD – – – – –
of 1 odour = NC
Cross Cultural – – – – – – – – – – – DLB < AD
Small
Identification Test

condition measuring attentional controlled search.
DLB patients were impaired in both conditions and
performed significantly worse than AD patients in
the parallel search condition. These results indicate
that patients with DLB exhibit an early, pre-
attentive deficit in visual processing.
Relation between Visual Impairments
and Visual Hallucinations
One of the main diagnostic criteria for DLB is
visual hallucination, which is observed in up to
80% of patients and usually co-exists with
perceptual difficulties (McKeith et al., 2000a).
McKeith et al. (2004b) found that DLB patients
with visual hallucinations showed larger benefits in
simple and choice reaction time tasks from
rivastigmine, a ChEI drug, than DLB patients
without hallucinations. Other studies suggest a
possible link between visual perceptual
impairments and the clinical feature of visual
hallucinations. For instance, Mosimann et al.
(2004) found PDD and DLB patients with visual
hallucinations to be significantly more impaired in
visual perception than patients without
hallucinations. Mori et al. (2000) found that DLB
patients with visual hallucinations performed worse
in an overlapping figures task relative to those
without hallucinations. Similarly, Simard et al.
(2003) reported that DLB patients with
588 Claudia Metzler-Baddeley
predominant psychosis (e.g., hallucinations) were
making more perceptual errors in Benton’s
Judgement Line Orientation Test in comparison to
DLB patients with predominant Parkinsonism who
made more attentional errors.
Possible Underlying Pathology of Visual-Perceptual
Impairments
The neuropsychological findings summarised
above indicate early and pronounced visual-
perceptual impairments affecting object and space
perception in DLB. Matched patients with PDD
tend to demonstrate similar deficits whereas
matched patients with AD tend to perform
normally on these tasks. Findings of impaired
visuo-perception are consistent with results from
imaging studies reporting reduced glucose
metabolism and blood flow in the occipital lobes,
including primary visual cortex and visual
association cortex in DLB patients compared to AD
patients (Colloby et al., 2002; Gilman et al; 2005;
Imamura et al., 1997; Ishi et al., 1998, 1999).
Walker et al. (1997) also reported significant
reduction in striatal uptake of a ligand for the
presynaptic dopamine transporter site in DLB but
not in AD. It has been suggested that reduced
activity in occipital regions might be linked to
spongiform changes in the white matter of DLB
patients which primarily affect occipital regions
(Higuchi et al., 2000). Reduced activity however
also may be linked to the marked cholinergic
deficit in DLB that is known to affect occipital and
temporal regions (Perry et al., 1994). Cholinergic
and possibly dopaminergic dysfunctions in the
cerebral cortex has also been associated with the
occurrence of visual hallucinations (Court et al.,
2001; McKeith et al., 2004b; Perry et al., 1990).
Furthermore, post-mortem pathological studies
found LB pathology in the temporal lobes
associated with visual hallucinations (Harding et
al., 2002) whereas AD pathology such as tangles,
tended to be less related (Merdes et al., 2003).
Calderon et al. (2001) interpreted their findings
of visual-perceptual deficits in the VOSP within
Ungerleider and Mishkin’s (1982) framework of
two streams of visual analysis. Both ventral and
dorsal streams start in the striate cortex, but begin
to diverge in the extrastriate cortex. The ventral
pathway projects downwards from primary visual
to visual association areas in the inferior temporal
region. The ventral stream mediates object
recognition by relating visual information to stored
semantic knowledge about the perceived object, i.e.
recognises what an object is. The dorsal pathway
projects upwards into the posterior parietal cortex
and mediates complex visual-spatial analysis such
as identifying the location of an object in space,
i.e. recognises where the object is located. Since
DLB patients have been found to be impaired both
in ventral (e.g., fragmented letters) and dorsal tasks
(e.g., cube analysis), they appear to suffer from
disrupted processing in both streams. There is also
evidence that performance in parallel search tasks,
such as the one employed in Cormack et al.’s
(2004b) study can be disrupted by lesions in parts
of the occipito-temporal cortex (Humphreys et al.,
1992), whereas occipito-parietal lesions affect
serial search (Atkinson and Bradrick, 1989).
Cormack et al.’s (2004b) findings therefore also
suggest that DLB patients are affected in occipito-
parietal and occipito-temporal areas with a
particular impairment in the latter region.
It is generally thought that a number of
hierarchical intermediate processing steps are
involved between the processing of visual
information in the eye and the formation of object
representations mediated in cortical areas (e.g.,
Humphreys and Riddoch, 1993). As a very first
crude approximation, light is individually spatially
band pass filtered in retinal ganglion cells, and is
then processed by orientation selective cells in V1
(Hubel and Wiesel, 1959, 1960). These orientation
selective cells interact by horizontal connections
and after some intermediate processing the results
of this process are used to form object
representations in the inferior temporal cortex. The
evidence so far indicates that DLB patients suffer
from early visual-perceptual deficits, affecting
object and space perception due to lesions in
occipital and surrounding regions. However, it has
not been systematically investigated yet which
visual processing stages are specifically affected, or
if all of them are impaired in DLB.
Furthermore it is unclear how visual perceptual
deficits are linked to the clinical feature of visual
hallucinations. Related evidence from PD research
demonstrated that PD patients with visual
hallucinations show greater deficits in visual object
perception, recognition, and recollection of the
encoding episode than PD patients without
hallucinations (Barnes et al., 2003). However,
visual imagery and spatial perception did not differ
between both groups, suggesting that a
combination of faulty perceptual processes other
than image generation and less detailed recollection
of episodes might underlie visual hallucinations
(Barnes et al., 2003).
Olfactory Perception
There is evidence that deficits in olfactory
perception may be linked to LB pathology (for a
review see Katzenschlager and Lees, 2004). Odour
identification deficits are well established in PD,
and have also been reported in AD and a few
studies have recently investigated odour
identification in DLB. Westervelt et al. (2003)
found DLB patients to perform significantly worse
than AD patients in an odour identification task
(the Cross-Cultural Small Identification Test).
McShane et al. (2001) tested single odour
 Cognitive deficits in Lewy body dementia
identification in DLB patients and healthy elderly
controls. Post mortem neuropathological
examination revealed that anosmia in life was only
associated with LB, but not with AD pathology. In
addition, the overall cortical LB scores and LB
density in the cingulate were higher in anosmic
cases. Gilbert et al. (2004) recently tested
recognition and remote memory for olfactory and
visual stimuli in DLB and AD patients. Both
groups performed significantly worse than control
participants with DLB patients’ remote memory for
odours being more impaired than AD patients’
odour memory, and visual memory being equally
affected. It has therefore been suggested that odour
identification and memory tasks (Gilbert et al.,
2004; Katzenschlager and Lees, 2004) could be
used to aid differential diagnosis of diseases with
LB or AD pathology.
Possible Underlying Pathology
of Olfactory-Perception Impairments
The underlying pathology of anosmia is not
well understood yet. It has been suggested that LB
pathology in the olfactory nucleus and the
amygdale is involved in olfactory dysfunction (see
Katzenschlager and Lees, 2004). There is recent
evidence that dopamine levels were elevated in the
olfactory bulb in PD patients (Huisman et al.,
2004) which may suppress the transmission
between olfactory receptors and mitral cells in the
olfactory glomeruli (Duchamp-Viret et al., 1997).
Summary of Perception
Overall, the evidence so far indicates that DLB
patients are more impaired in visual-perceptual and
visual-constructive tasks than AD patients. The
results of some of the earlier studies are difficult to
interpret, since the tests used were complex and
visual-perception was confounded with other
functions such as attentional, executive and
memory functions. However, the observation that
copying is impaired in DLB but not in AD whereas
both groups are impaired in drawing from memory
suggests that DLB patients perform badly on both
tests due to visual perceptual deficits (and possibly
additional memory problems) whereas AD patients
perform poorly due to a memory deficit.
Furthermore, findings of impaired object and space
perception (Calderon et al., 2001; Lambon-Ralph et
al., 2001; Mosimann et al., 2004; Noe et al., 2004),
and poor parallel search (Cormack et al., 2004b)
indicate a more pronounced and earlier visual-
perceptual deficit than in AD. In contrast, patients
with PDD exhibit similar visuo-perceptual and
visuo-constructive impairments as DLB patients
(Cormack et al., 2004a; Mosimann et al., 2004;
Noe et al., 2004). Perceptual deficits in DLB are
probably linked to lesions in occipital-temporal and
occipito-parietal areas. These structures have also
589
been found to be affected in imaging studies. There
also seems some preliminary evidence that visual-
perceptual deficits and the occurrence of visual
hallucinations are related.
Finally, patients with DLB exhibit difficulties in
odour identification and recognition, similar to
patients with PD. However, the precise nature and
locus of visual and olfactory impairments, as well
as the link to clinical features such as
hallucinations, requires further investigation with
more theoretically driven tests such as those used
by Cormack et al. (2004b). More research is also
required to evaluate the potential clinical value of
these and other laboratory-based tasks to aid
differential diagnosis of DLB.
ATTENTION AND EXECUTIVE FUNCTIONING
Attention is a multi-dimensional concept that
describes different aspects of processing and
responding to information including automatic
processes such as visual orienting and higher-level
processes of attentional control. Executive function
is a loosely defined term referring to control
aspects of attention. Norman and Shallice (1986)
distinguished between automatic, habitual control
of behaviour and an attentional, supervisory control
system (the supervisory activating system – SAS)
that can intervene if routine control does not meet
situational demands. The SAS is very closely
related to the central executive component of
Baddeley and Hitches’ (1974) working memory
model (see below). There is evidence that SAS or
central executive can be fractionated in a number
of functions such as focusing attention, dividing
attention, switching attention, and inhibition of
irrelevant information, which are all associated in
humans with frontal lobe processing (Knight and
Stuss, 2002; Shallice, 1988). Table III gives an
overview of studies that have investigated attention
and executive functions in DLB (see also Collerton
et al., 2003; Lambon-Ralph et al., 2001; Simard et
al., 2000).
Calderon et al. (2001) tested DLB patients on
the Test of Everyday Attention (TEA) and
demonstrated deficits in selective, sustained, and
divided attention that exceeded those found in AD
patients on some, though not all components. In
this study, tests involving visual attention appeared
to be most vulnerable to DLB. As mentioned
above, Cormack et al. (2004b) have found DLB
patients more impaired in visual tasks measuring
attentional controlled serial search than AD
patients. Noe et al. (2004) compared DLB, PDD,
and AD patients’ performance in two cancellation
tasks involving the detection of a shape or a
consonant trigram from a sequence of shapes or
phonemic distractors. These tasks measured the
ability to suppress distraction within the visual
field. DLB patients performed significantly slower
590 Claudia Metzler-Baddeley

TABLE III
Overview of neuropsychological findings for attention and executive functions

Aarsland Ala et al. Ballard Ballard Calderon Cormack Doubleday McKeith Noe Perriol Walker
et al. (2001, et al. et al. et al. et al. et al. et al. et al. et al. et al.
(2003) 2002) (2001) (2002) (2001) (2004b) (2002) (2004b) (2004) (2005) (2000b)
MMSE: attention – DLB < – – – – – – – – –
AD
DRS: initiation DLB = – – – – – – – – – –
PDD <
AD
DRS: perseveration DLB = – – – – – – – – – –
PDD <
AD
General attention – – – – – – DLB < AD – – – –
Visual distraction – – – – – – DLB > AD – – – –
Auditory distraction – – – – – – DLB = AD – – – –
Set establishment – – – – – – DLB < AD – – – –
Set shifting – – – – – – DLB < AD – – – –
Incoherence – – – – – – DLB > AD – – – –
Confabulation – – – – – – DLB > AD – – – –
Perseveration – – – – – – DLB > AD – – – –
Intrusions – – – – – – DLB > AD – – – –
Serial search – – – – – DLB = AD – – – – –
< PD
CDR: Simple RT – - DLB > DLB = – – – DLB - - -
(SD) AD > NC PDD > AD (hallucinators)
= PD > NC > DLB (non-
hallucinators)
on ChE
CDR: Choice RT – – DLB > DLB = – – – DLB – – DLB >
(SD) AD > NC PDD > AD (hallucinators) VD > AD
= PD > NC > DLB (non-
hallucinators)
on ChE
CDR: Digit – – DLB > – – – – – – – DLB >
vigilance RT (SD) AD > NC VD > AD
TEA: sustained – – – – DLB < – – – – – –
attention AD = NC
TEA: auditory – – – – DLB = – – – – – –
selective attention AD < NC
TEA: visual – – – – DLB < – – – – – –
selective attention AD < NC
Shape cancellation – – – – – – – – DLB = – –
PDD <
AD
Consonant – – – – – – – – DLB = – –
cancellation PDD <
AD
Stroop – – – – DLB < – – – – – –
AD < NC
Nelson’s card – – – – DLB < – – – – – –
sorting AD < NC
Letter fluency – – – – DLB < – – – – – –
AD < NC
PPI of auditory – – – – – – – – – DLB < -
evoked potentials PDD <
AD = NC

than AD patients in both tasks and showed a
greater number of errors in the shape cancellation
task. In contrast, no difference between DLB and
PDD patients was found. All of these studies
indicate a disruption of attention in the visual
modality in DLB.
However, a recent EEG study by Perriol et al.
(2005) demonstrated that prepulse inhibition (PPI)
of N1/P2 of auditory evoked potentials was
severely disrupted in DLB patients and moderately
disrupted in PDD patients in comparison to AD
patients and healthy controls. PPI is thought to
reflect the ability to filter out irrelevant sensory
and cognitive information, thus DLB patients, and
to a lesser degree, PDD patients, appear to have a
deficit in the inhibitory component of attentional
control. Perriol et al.’s (2005) study also indicates
that DLB patients suffer from attentional
dysfunction independent of their visual-perceptual
impairments, although it is plausible that perceptual
impairments exacerbate difficulties in visually
based attention tasks. Non-visual attentional
deficits have also been reported in standard tests
such as the MMSE in which DLB patients have
 Cognitive deficits in Lewy body dementia
been found to perform more poorly in counting and
spelling backwards than AD patients (Ala et al.,
2002).
A number of earlier studies (see Collerton et al.,
2003; Lambon-Ralph et al., 2001; Simard et al.,
2000) have shown that DLB patients are severely
impaired in more complex “frontal-executive” tests,
such as Stroop, letter fluency, card sorting, and trail
making tests. Some studies found more severe
impairment in DLB (e.g., Calderon et al., 2001)
than AD whereas other studies report similar
impairments (e.g., Noe et al., 2004). Differences
between studies can most likely be accounted for
by different task demands and by variation in
dementia severity between the patient groups.
Further evidence for frontal-executive
impairment in DLB, however, comes from a study
by Doubleday et al. (2002) who compared
qualitative performance characteristics during
neuropsychological testing of patients with DLB
and AD. DLB patients were less able to maintain
vigilance and attention, were more easily distracted
by visual stimuli, had problems with initially
engaging in tests and shifting mental set between
tests. They showed more incoherent lines of
thought, more confabulation, and perseveration and
produced environmentally cued intrusions, all
characteristic features of dysexecutive impairment.
These observations are consistent with Aarsland et
al.’s (2003) study who found patients with DLB
and PDD to score lower in the initiation and
perseveration subtests of the Dementia Rating
Scale (DRS) than patients with AD. However in
the same study, DLB patients with mild to
moderate dementia were reported to score
significantly lower in the DRS conceptualisation
subtest than matched patients with AD and PDD.
Possible Pathology of Attentional
and Executive Impairments
Different attentional functions can be
functionally and anatomically separated and it has
been therefore suggested that attention is carried
out by a network of anterior and posterior
anatomical areas (Posner and Petersen, 1990). One
of the regions involved in the modulation of
attention is the basal forebrain cholinergic system
(BFCS) that provides the major cholinergic
innervations to the cortex and other regions such as
the thalamus, the prefrontal cortex, and the parietal
lobes (Lawrence and Sahakian, 1998). DLB
patients suffer from a pronounced cholinergic
disruption, involving the BFCS (Lemstra et al.,
2003) and there is some evidence that ChEI
medication may have beneficial effects on attention
and disturbances of consciousness in DLB. DLB
patients also demonstrate LB pathology in frontal
and cingulate areas that are classically related to
executive aspects of attention such as focused
attention, attention switching and distractor
591
suppression. Furthermore, as mentioned above, LB
pathology can affect occipito-parietal and occipito-
temporal regions and is therefore likely to affect
automatic aspects of attention mediated by
posterior regions such as visual orienting and
engaging/disengaging of attention.
Cognitive Fluctuation
Attentional impairments in DLB manifest
themselves in everyday life as cognitive
fluctuations, one of the core diagnostic features of
DLB. Clinical tools to measure cognitive
fluctuations are based on semi-structured interviews
with patients’ carers who rate the presence,
frequency, severity and quality of cognitive
fluctuations during the month prior to the
assessment (e.g., Clinician Assessment of
Fluctuation; Walker et al., 2000a) or a
questionnaire querying symptoms of fluctuations
and delirium (Fluctuations Composite Scale;
Ferman et al., 2004). Bradshaw et al. (2004)
investigated quantitative and qualitative
characteristics of cognitive fluctuations in DLB and
AD using the Clinician’s Assessment of Fluctuation
Scale. They found that 77% of DLB patients in
comparison to none of the AD patients exhibited
clinically significant fluctuations. Whereas
fluctuation in AD were primarily memory related
deficits such as confusion, forgetfulness, and
repetitiveness in situations that were demanding on
memory, DLB patients’ fluctuations tended to be
lapses in awareness and attention (i.e., ‘going
blank’), which were more short-lived, occurred
spontaneously and were unrelated to situational
demands. Similarly, Ferman et al. (2004) on the
basis of the Fluctuations Composite Scale reported
that DLB relative to AD patients’ fluctuations were
more characterised by daytime drowsiness,
lethargy, and sleeping, as well as staring into space
and episodes of disorganised speech.
Recent studies have explored the nature of
cognitive fluctuations by investigating short-lived
fluctuations in attentional tasks, which may reflect
an experimental equivalent to the more long-term
clinical fluctuations. Ballard et al. (2001, 2002) and
Walker et al. (2000b) used simple and choice
reaction time (RT) tasks and vigilance tasks from
the Cognitive Drug Research Test battery (CDR)
and measured attentional fluctuations through
variation of reaction times within and between
testing sessions. Walker et al. (2000b) compared
attentional fluctuation in DLB patients with
patients with AD and vascular dementia. Although
all groups demonstrated fluctuations, DLB patients
showed the greatest variability, with the differences
being most marked in the shortest 90 seconds task.
Ballard et al. (2001) replicated this finding and
demonstrated that DLB patients’ short-term
fluctuations in attention tasks correlated
significantly with clinical fluctuations, as measured
592 Claudia Metzler-Baddeley
by the Clinician’s Assessment of Fluctuation Scale.
Finally, in a third study, Ballard et al. (2002)
extended their findings to PD and PDD patients
and demonstrated that DLB and PDD patients
show a very similar pattern of attentional
fluctuation which differs significantly from that
found with AD and PD patients.
Summary of Attention and Executive Functions
DLB and AD patients are both impaired in
attentional and executive tasks, but in DLB the
deficits appear to be more generalised and more
pronounced to the extent that patients cannot
perform some of the tasks at all (e.g., Calderon et
al., 2001). DLB patients tend to be more impaired
in visual attentional tasks (Calderon et al., 2001),
probably due to their pronounced visual-perceptual
deficits. However, as Perriol et al.’s (2005) study
demonstrates, attentional deficits are not restricted
to one domain and therefore cannot solely be
explained in terms of perceptual impairments. Up
to now, the nature, the extent, and the underlying
neural correlate of attentional deficits in DLB are
not well understood and more theoretically-driven,
experimental work is required to answer these
questions.
There is evidence that DLB patients’
performance in cognitive tasks fluctuates more
severely than AD patients’ performance and this is
particularly the case in attentional tasks in which it
has been found to continuously vary on a second to
second basis (Ballard et al., 2001, 2002; Walker et
al., 2000b). More research is required to investigate
the link between such short-term fluctuations and
the more long-term clinical cognitive fluctuations
and to assess the potential clinical value of brief
experimental tasks for differential diagnosis.
MEMORY
Memory can be divided into different systems
that can be functionally and anatomically separated
(Aggleton and Brown, 1999). The broadest
memory dichotomy is between short-term or
working memory and long-term memory (Atkinson
and Shiffrin, 1968). Working memory (Baddeley
and Hitch, 1974) generally refers to the act of
being aware of the present, the ability to bring
information stored in memory back to our
consciousness, and to manipulate this information.
Long-term memory refers to information stored in
memory that requires varying degrees of effort to
be retrieved. Tulving (1983) introduced the
distinction between episodic memory (memory for
discrete personal events), semantic memory
(concerned with language and our general
knowledge about the world), and procedural
memory (any form of memory that is difficult to
explain with language and is usually expressed as
action or motor skill). The following sections will
discuss studies that have investigated working
memory, episodic and semantic memory in DLB
(see Table IV), whereas, to the best of the author’s
knowledge, no evidence on procedural memory in
DLB is available.
Working Memory
The revised working memory model by
Baddeley (2003) consists of four components: 1)
The phonological loop, which is a phonological
store that can hold information for a few seconds
before they fade. The phonological loop mediates
articulatory rehearsal analogous to subvocal speech
and is limited in capacity. The capacity of the
phonological loop is usually assessed with the digit
span task. 2) The visuo-spatial sketchpad represents
the visuo-spatial equivalent of the phonological
loop. The capacity of the visuo-spatial sketchpad is
usually assessed with the Corsi block span task. 3)
The central executive, which represents the overall
attentional control systems. Different aspect of the
central executive task can be measured with various
tasks, as listed in the previous section, but the
ability to carry out two tasks simultaneously is often
used as a measure for executive functioning. 4) The
most recent addition to the model is the episodic
buffer, which provides an interface between the
different components of working memory and
different systems of long-term memory.
As summarised above, DLB patients’ suffer
from extensive attentional and executive
impairments. It is therefore not surprising that they
have been reported to perform poorly in some
working memory tasks, although the evidence
remains mixed. A number of studies have compared
DLB and AD patients in verbal and spatial span
and found DLB patients to be equally, or possibly
more severely impaired than AD patients (see
Collerton et al., 2003; Lambon-Ralph et al., 2001;
Simard et al., 2000). Calderon et al. (2001) tested
DLB and AD patients on a dual performance task
that involves individual and simultaneous
assessment of digit span and visual tracking. Both
groups performed normally in the span task and the
AD patients performed better than the DLB patients
in the box cancellation task. However, DLB
patients exhibited less decrement in performance
due to the dual task than the AD patients. In
contrast, Simard et al. (2002) reported DLB patients
to perform more poorly in the span/tracking dual
task than AD patients, whereas AD patients were
more impaired in a spatial dual task which involved
walking and talking at the same time.
Possible Underlying Pathology of Working Memory
Impairment
There is evidence from lesion and imaging
studies that relate the phonological loop to the left
 Cognitive deficits in Lewy body dementia 593

TABLE IV
Overview of neuropsychological findings for memory

Aarsland Ala et al. Calderon Gilbert Hamilton Lambon-Ralph Noe Simard

et al. (2003) (2002) et al. (2001) et al. (2004) et al. (2004) et al. (2001) et al. (2004) et al. (2002)
Working memory
Dual task: Digit span – – DLB > AD – – – – DLB < AD
and visual tracking
Dual task: walking – – – – – – – DLB > AD
and talking

Episodic memory
DRS: memory AD < DLB = – – – – – – –
PDD < PSP
MMSE: memory – DLB = AD – – – – – –
CVLT: immediate – – – – DLB = AD – – AD < DLB
free recall < NC < NC
CVLT: immediate – – – – – – – AD < DLB
cued recall < NC
CVLT: delayed – – – – DLB = AD – – AD < DLB
free recall < NC < NC
CVLT: delayed – – – – – – – AD < DLB
cued recall < NC
CVLT: recognition – – – – AD < DLB – – –
< NC
BSRT: total recall – – – – – – AD < DLB –
= PDD
BSRT: delayed recall – – – – – – AD < DLB –
= PDD
BSRT: delayed – – – – – – AD < DLB –
recognition = PDD
WMS-R: LM – – AD < DLB – DLB = AD – – –
immediate recall < NC < NC
WMS-R: LM – – AD < DLB – DLB = AD – – –
delayed recall < NC < NC
RMT: words – – DLB = AD – – DLB = AD – –
< NC < NC
RMT: faces – – DLB = AD – – DLB = AD – –
< NC < NC
Benton visual – – – – – – DLB = PDD –
retention tests < AD
Odour recognition – – – DLB = AD – – – –
< NC
Faces recognition – – – DLB = AD – – – –
< NC
Symbol recognition – – – DLB = AD – – – –
< NC
Odour remote – – – DLB < AD – – – –
memory < NC
Faces remote memory – – – DLB = AD – – – –
= NC
Symbol remote – – – DLB = AD – – – –
memory = NC

Semantic memory
Graded Naming Test – – – – – DLB < AD – –
< NC
Picture naming – – – – – DLB = AD – –
< NC
Spoken word to – – – – – DLB < AD – –
picture matching = NC
CCT: pictures – – – – – DLB < AD – –
< NC
CCT: words – – – – – DLB < AD – –
< NC
Category sorting – – – – – DLB < AD – –
pictures = NC
Category sorting – – – – – DLB < AD – –
words = NC
Category fluency – – – – – DLB = AD – –
< NC
Note. CCT = Camel and Cactus Test.
594 Claudia Metzler-Baddeley
temporo-parietal region (for a review see Baddeley,
2003). More specifically, area BA 40 has been
associated with the storage component of the loop
and Broca’s area with the rehearsal component. In
contrast, visuo-spatial working memory is primarily
located on the right hemisphere, in particular the
right inferior parietal cortex, right premotor cortex,
the right inferior frontal cortex, and the anterior
extrastriate occipital cortex. Various executive
functions, such as task switching or response
suppression have been found to be associated,
though not exclusively, with a number of regions
within the prefrontal cortex, such as dorsolateral,
inferior, and medial regions including the anterior
cingulate.
There are no studies that have attempted to
tease apart the different working memory
components in DLB and link them to the pathology
associated with the disease. LB pathology in DLB
is known to be concentrated in frontal, temporal,
and parietal regions as well as in subcortical
structures including brain stem nuclei and
components of the BFCS. Thus, as a very crude
speculation, given the widespread pathology, one
might expect all aspects of working memory to be
impaired. However, Calderon et al. (2001) and
Simard et al. (2002) studies suggest that DLB
patients may perform under certain dual task
conditions better than AD patients. Thus, it remains
to be clarified if DLB affects some components of
working memory more than others, and how such
impairments are related to perceptual and
attentional deficits and to the pathology associated
with DLB.
Episodic Memory
Episodic memory is usually assessed with
immediate and delayed free or cued recall and to
varying degrees with recognition tasks (Mandler,
1980). DLB patients suffer from episodic memory
impairment, however, their mnestic problems tend
to be less severe than the amnesia observed in AD.
In general, DLB patients perform better than AD
patients in verbal recall tasks such as Logical
Memory from the WMS-R (Calderon et al., 2001),
the California Verbal Learning Test (CVLT)
(Simard et al., 2002), the Buschke Selective
Reminding Test (BSRT; Noe et al., 2004) and
various recall subtest in tests of general cognitive
impairment (e.g., MMSE, DRS) (Aarsland et al.,
2003; Ala et al., 2002; see Collerton et al., 2003;
Lambon-Ralph et al., 2001; Simard et al., 2000).
This is in particular the case for delayed verbal
recall, although some studies have reported
superior immediate recall too. Furthermore,
Aarsland et al. (2003) and Noe et al. (2004) report
no difference in verbal recall between DLB and
PDD patients.
However, in tests requiring the recall of visual
material such as the visual reproduction tests in the
WMS-R or the CAMCOG visual memory test (see
Collerton et al., 2003; Lambon-Ralph et al., 2001;
Simard et al., 2000), DLB patients were found to
be as impaired as AD patients. The comparison
between visual and verbal recall in DLB suggests
that visual-perceptual problems might contribute to
poor performance in visually based memory task.
However, the contribution of perceptual and
memory effects on performance in recall task has
not been separated yet. Thus it is not known to
what extent poor recall in DLB reflects impaired
memory processing.
Hamilton et al.’s (2004) suggested that DLB
patients’ poor memory might primarily be a result
from impaired encoding rather than from defective
consolidation. DLB and AD patients tested on the
CVLT and the WMS-R Logical Memory Test were
both impaired on immediate and delayed recall.
However, DLB patients showed significantly better
saving scores in both tests and also performed
better on the CVLT recognition tests, indicating
that once DLB patients had learned the information
it could be retained relatively well (see also
Salmon et al., 1996).
Recognition memory is known to rely to
varying degrees on episodic retrieval and on
judgments regarding the familiarity of an item
(Mandler, 1980). There are mixed results regarding
recognition memory in DLB relative to AD.
Calderon et al. (2001) and Lambon-Ralph et al.
(2001) found both AD and DLB patients perform
significantly worse than healthy control participants
in the Recognition Memory Test (RMT) for faces
and words (see also Shimomura et al., 1998).
Hamilton et al. (2004) however reported DLB
patients to perform better than AD patients in the
recognition tests of the CVLT whereas in Noe et
al.’s (2004) study, DLB and PDD patients
performed worse in visual recognition than patients
with AD.
Finally, Gilbert et al. (2004) found DLB and
AD patients significantly impaired in recognition
memory for olfactory and visual stimuli (faces and
symbols), with DLB patients being in particular
impaired for odours. The same study investigated
remote memory for visual and olfactory stimuli,
measured as familiarity ratings. There was no
difference between DLB, AD and healthy control
for visual material. However, DLB and AD patients
relative to controls were significantly impaired in
remote memory for odours and DLB patients
performed significantly worse than AD patients in
this task.
In the case of recognition memory, it is not
clear if DLB patients are as impaired as AD
patients due to an episodic memory problem and/or
a problem in familiarity judgement. Gilbert et al.’s
(2004) study suggests that familiarity judgement
can be preserved in DLB for some material.
Furthermore, it is not known to what extent
additional cognitive impairments in particular
 Cognitive deficits in Lewy body dementia
perceptual and attentional deficits contribute to
poor recognition performance in DLB. Gilbert et
al.’s (2004) findings suggest that DLB patients
have a particular problem with olfactory stimuli
that may exceed the one for visual material.
Possible Underlying Pathology of Episodic Memory
Impairment
Memory functions are known to be mediated by
a network of cortical regions within the temporal
and frontal lobes and subcortical areas including
the hippocampus, thalamic nuclei, and the
mamillary bodies of the hypothalamus (Aggleton
and Brown, 1999; Aggleton and Pearce, 2001).
Aggleton and Brown (1999) proposed that an
“extended hippocampal system” comprising the
hippocampus, the fornix, the mamillary bodies of
the hypothalamus, and the anterior thalamic nuclei,
are crucial for encoding and storage, and hence
subsequent recall of episodic memory. In contrast
recognition memory based on familiarity
judgements was suggested to depend on the
perirhinal cortex of the temporal lobe and the
medial dorsal nucleus of the thalamus. When both
systems are affected, as it is the case in
anterograde amnesia, the result is a severe deficit
in both recall and recognition.
In patients with AD, pathological changes affect
preferentially medial-temporal structures such as
entorhinal cortex and the surrounding neorcortical
association areas, thus resulting in severe episodic
memory impairment. Magnetic resonance imaging
(MRI) studies have found a relative preservation of
hippocampal, medial temporal lobe and orbito-
frontal structures in DLB compared to AD
(Ballmaier et al., 2004; Barber et al., 1999, 2000;
Hashimoto et al., 1998). In addition, Burton et al.
(2004) reported AD patients to show more
significant volumetric loss in the temporal lobes
and the hippocampus than patients with DLB and
PDD, who demonstrated a similar picture of
cerebral atrophy involving occipital, temporal, right
frontal and left parietal regions. An MRI study by
Tam et al. (2005) reported medial temporal atrophy
in PDD, DLB and AD patients. Patients with AD,
and, to a lesser extent, patients with DLB showed
most pronounced atrophy. The extent of atrophy
correlated with CAMCOG and memory scores in
the DLB group but not in the other groups. These
findings indicate that brain structures mediating
episodic memory are affected in DLB, to a lesser
degree than in AD, but to a larger degree than in
PDD.
At present it is not known, if impairments in
recall and recognition in DLB reflect underlying
problems in episodic memory and/or familiarity
judgement, or are caused by additional perceptual
and attention/executive problems. There is also
only preliminary evidence from one study
(Hamilton et al., 2004) suggesting that
595
consolidation processes mediated within the
hippocampus and surrounding areas might be less
affected in DLB than AD. Thus, until more light
has been shed on the underlying neuropsychology
of memory impairment in DLB it remains difficult
to speculate on relevant pathological changes.
Semantic Memory
DLB and AD patients tend to be equally
impaired in category fluency, in naming tasks such
as the Graded Naming Test or the Boston Naming
Test, and in WAIS-R subtests that rely on semantic
knowledge (see Collerton et al., 2003; Lambon-
Ralph et al., 2001; Simard et al., 2000). For
instance, in Noe et al.’s (2004) study no difference
in verbal fluency was found between DLB, AD,
and PDD patients. Lambon-Ralph et al. (2001)
found DLB patients equally impaired in category
and letter fluency whereas AD patients performed
significantly better with letters than categories. The
authors interpreted this pattern as reflecting a
semantic retrieval problem in AD that primarily
affects category fluency and an attentional
executive impairment in DLB that affects fluency
regardless of the generated material. The same
study also identified a possible contribution of
visual-perceptual deficits since DLB patients
performed worse for pictures than words whereas
control participants and AD patients showed no
picture-word differences. DLB patients also
performed worse than AD in a spoken word to
picture matching task and a category sorting task
(Lambon-Ralph et al., 2001).
Possible Underlying Pathology of Semantic Memory
Impairment
Neuroimaging studies indicate (see for review
Thompson-Schill, 2003) that semantic memory
is mediated by a large, distributed network
including areas in the prefrontal cortex in particular
the left inferior frontal gyrus, the premotor cortex,
anterior, ventral and lateral regions of the temporal
cortex, and the parietal cortex. All of these
neocortical areas can be affected in patients
with DLB. However, there is only limited evidence
so far regarding which aspects of semantic
processing are impaired in DLB, and how these
relate to perceptual and attention-executive
impairments.
Summary of Memory
Most studies on working memory found DLB
patients equally or more impaired than AD
patients. Both groups are also impaired on episodic
and semantic memory tests, although DLB patients
usually perform better in verbal recall in particular
after a delay. A problem in interpreting present
evidence on memory impairments in DLB is the
596 Claudia Metzler-Baddeley
difficulty in teasing apart the contribution of
perceptual deficits and attentional-executive
impairments to the memory performance. DLB
patients’ extensive perceptual deficits may have a
detrimental effect on performance in visual and
olfactory memory tasks. In addition, attentional-
executive problems appear to interfere with the
encoding of information which in turn can lead to
poor memory performance (Hamilton et al., 2004).
Further investigation is required to tease apart the
effects of perceptual and attentional impairments
on memory performance to identify the extent and
the nature of possible mnestic impairments in
DLB. A starting point may be to test DLB patients
in matched memory tests for different modalities
such as the Doors and People Test (Baddeley et al.,
1994), that provides separate measures for recall
and recognition in the visual and verbal domain.
Furthermore, it remains to be clarified which
aspects of memory processing, such as encoding,
storage, retrieval, and familiarity judgements may
be impaired in DLB.
GENERAL DISCUSSION
At the moment, research concerned with
cognitive, clinical, pathophysiological or imaging
aspects of DLB has been carried out more at the
empirical than at the theoretical level. Given that
DLB is a relatively new disease concept, most of
the work so far has been concerned with the first
step of characterisation and description of DLB as
a separate disease. Most of the studies suggest, that
in the early stages of the disease, DLB patients
tend to exhibit pronounced visual-perceptual,
attentional and frontal executive impairments
whereas memory functions are generally less
impaired than in AD (Collerton et al., 2003;
Dalrymple-Alford, 2001; Noe et al., 2004).
However, given the overlap and variability of
symptoms, the neuropsychological profile of DLB
has not yet been clearly distinguished from that of
AD (Knopman et al., 2001). Furthermore, DLB and
PDD patients demonstrate similar cognitive
impairments in comparison to patients with AD
(Aarsland et al., 2003, 2004; Ballard et al., 2002;
Noe et al., 2004).
Studies so far have primarily used standard
neuropsychological tests, which initially are
appropriate to outline DLB patients’ cognitive
profile but have the drawback that they are often
difficult to interpret theoretically. For instance, tests
of visual perception may also rely on attentional-
executive and semantic memory functions. Memory
tests may, in turn depend on perceptual, attentional
and executive functions, making it difficult to
separate and analyse any further memory problems.
Thus although the broad cognitive profile in DLB
has now been well described, little is known in
detail about the precise nature of these
impairments. Further progress will require the use
of more specific, theoretically motivated tests, a
process which is just beginning (e.g., Cormack et
al., 2004b). Such tests would allow better
understanding of the nature of cognitive
impairments in DLB and would allow the
evaluation of neuropsychological data within
current frameworks of cognition. Carefully
designed cognitive tests may also allow the
investigation of theoretical questions about the
normal organisation of cognitive functions. In
addition, better understanding of cognitive
impairments associated with DLB may provide
valuable information for patients and carers and
may lead to the development of suitable screening
tests to aid clinical diagnosis.
Sensitivity of DLB diagnosis still remains poor
because of the variability and overlap of symptoms
between different diseases, but also because it has
been proven difficult to characterise and assess the
core clinical features of cognitive fluctuations and
visual hallucinations. More work is required to
investigate the nature of fluctuations and
hallucinations, for instance, by clarifying the
relation between clinical features and cognitive
measures of perceptual and attentional function
(Ballard et al., 2001, 2002; Walker et al., 2000b).
There is some preliminary evidence that within-
trial variability in attentional tasks and everyday
cognitive fluctuations as assessed by clinical
measures may be related to each other (Ballard et
al., 2001) and it has been suggested that such brief
experimental tasks might be of value for
differential clinical diagnosis (Ballard et al., 2001,
2002; Walker et al., 2000b). Similarly, some studies
have reported a link between visual-perceptual
impairments and visual hallucinations (e.g.,
Mosimann et al., 2004; Simard et al., 2003) and it
has been suggested that the combination of
degraded vision and fluctuating attention might
lead to visual hallucinations (Calderon et al.,
2001). However, the investigation of such
hypotheses requires the recruitment of sufficiently
large patient groups that are monitored over a
substantial period of time. Given the relative rarity
of DLB and the difficulties with diagnosis this is
not an easy task and consequently most of the
studies so far have investigated relative small
groups of patients (see Table I). In the future, more
multi-centred studies need to be set up that co-
ordinate the recruitment and testing between
different clinics and allow the recruitment of large
enough patient samples to evaluate the clinical
value of different tests in aiding diagnosis.
The interpretation of the data so far, however, is
not only hampered by small sample sizes. In the
majority of studies, patients have been selected on
the basis of their clinical diagnoses, including
patients with “possible” diagnoses, which have not
been confirmed pathologically (see Table I). Given
the difficulties with clinical diagnosis of DLB, this
 Cognitive deficits in Lewy body dementia
opens the problem that some patients will have
been misdiagnosed and will therefore blur any
differences between the patients groups. There is
also an inherent conundrum in using clinical
diagnostic criteria to distinguish different patient
groups, and then use cognitive tests to re-
discriminate them. This is the case because clinical
diagnoses are implicitly or explicitly based on the
cognitive profile of patients themselves. It would
therefore be desirable for studies investigating
cognitive changes to select patients on the basis of
“independent” criteria such as biological markers,
or pathological findings. Until biological markers
or imaging tagging techniques are available
however, the only way to select different patient
groups in prospective studies is on the basis of
clinical diagnostic criteria. It is therefore important
to confirm clinical diagnoses with post-mortem
pathology.
Finally, only a few studies include information
about patient medication, i.e. if patients have been
on ChEI medication during cognitive assessment or
not (see Table I). Given the preliminary evidence
that ChEI may stabilise deficits in attention and
consciousness and visual hallucinations, it is
important to control for potential effects of
medication, in particular if medication differs
between the patient groups under comparison.
Ideally, in order to investigate the nature of early
cognitive impairments associated with the DLB,
patients should be tested before they are treated
with any medication.
Little is known so far about the pathogenesis
and development of DLB. Cummings (2003)
proposed that this may involve either of two
pathways. The first one begins with progressively
deteriorating dementia and presents clinically with
cognitive fluctuation and visual hallucinations. This
pathway is associated with possible LB pathology
in cortical and brainstem regions and with
dopaminergic deficits; it then progresses with the
additional development of Parkinsonism. The
second pathway begins with signs of PD; it then
progresses to dementia and neuropsychiatric
symptoms that are associated with cortical LB
pathology and cholinergic deficits. However, the
relationship between cortical LB pathology and
dementia is not well established and it is unclear if
the LB development represents a reaction of
healthy cells in response to biological stress, or
represents the underlying cause of impairment
(McKeith et al., 2004a).
In the future, the challenge of DLB research
will lie in developing a theoretical model that can
link evidence from pathophysiological and imaging
studies with clinical and neuropsychological data.
This will allow more specific hypotheses regarding
the development, progression, and treatment of the
disease to be formulated and tested, so that future
DLB patients will have access to appropriate
diagnosis, treatment and care.
597
Acknowledgements. I would like to thank Alan D.
Baddeley and three anonymous reviewers for their helpful
comments on this manuscript.
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Claudia Metzler-Baddeley, The Research Institute for the Care of the Elderly, St.
Martin’s Hospital Bath, BA2 5RP. e-mail: Claudia.Baddeley@bristol.ac.uk

(Received 17 March 2005; reviewed 19 April 2005; accepted 1 July 2005; Action Editor Jordan Grafman)