 |
|
Attention and Fluctuating Attention in Patients With Dementia With Lewy Bodies and Alzheimer Disease
Clive Ballard, MRCPsych, MD;
John O'Brien, MRCPsych, DM;
Alistair Gray, BSc;
Franchesca Cormack, BSc;
Gareth Ayre, PhD;
Elise Rowan, PhD;
Peter Thompson, MRCPsych;
Romola Bucks, PhD;
Ian McKeith, FRCPsych, MD;
Matthew Walker, PhD;
Martin Tovee, PhD
Arch Neurol. 2001;58:977-982.
ABSTRACT
| |
Background Attentional deficits are described in the consensus clinical criteria
for the operationalized diagnosis of dementia with Lewy bodies (DLB) as characteristic
of the condition. In addition, preliminary studies have indicated that both
attentional impairments and fluctuation of attentional impairments are more
marked in patients with DLB than in patients with Alzheimer disease (AD),
although neuropsychological function has not previously been examined in a
large prospective cohort with confirmed diagnostic accuracy against postmortem
diagnosis.
Methods A detailed evaluation of attention and fluctuating attention was undertaken
in 155 patients with dementia (85 with DLB and 80 with AD) from a representative
hospital dementia case register and 35 elderly controls using the Cognitive
Drug Research Computerized Assessment System for Dementia Patients computerized
neuropsychological battery. Operationalized clinical diagnosis was made using
the consensus criteria for DLB and the National Institute of Neurological
and Communicative Disorders and Stroke–Alzheimer's Disease and Related
Disorders Association criteria for AD. High levels of sensitivity and specificity
have been achieved for the first 50 cases undergoing postmortem examination.
Results The groups were well matched for severity of cognitive impairments,
but the AD patients were older (mean age, 80 vs 78 years) and more likely
to be female (55% vs 40%). Patients with DLB were significantly more impaired
than patients with AD on all measures of attention and fluctuating attention
(for all comparisons, t  2.5, P<.001), and patients from both dementia groups were significantly
more impaired than elderly controls for all comparisons other than cognitive
reaction time, which was significantly more impaired in DLB patients than
controls but was comparable in controls and AD patients. There were, however,
significant associations between the severity of cognitive impairment and
the severity of both attentional deficits and fluctuations in attention.
Conclusions This large prospective study confirms that slowing of cognitive processing,
attention, and fluctuations of attention are significantly more pronounced
in DLB and AD patients, although fluctuating attention is common in patients
with moderate-to-severe AD. Deficits of cognitive reaction time appear to
be specific to DLB, except in severe dementia. A detailed evaluation of attentional
performance could make an important contribution to differential diagnosis,
although the results need to be interpreted within the context of the overall
severity of cognitive deficits.
INTRODUCTION
LEWY BODIES are intraneuronal eosinophilic inclusion bodies that are
seen in the brainstem and cortex of patients with Parkinson disease and some
patients with dementia. Studies1, 2, 3, 4, 5, 6
have suggested that dementia with Lewy bodies (DLB) accounts for 10% to 25%
of dementia cases in clinical populations. An international meeting in 1996
developed operationalized clinical diagnostic criteria7;
key features included fluctuating cognition associated with disturbances of
consciousness, persistent or recurrent visual hallucinations, and parkinsonism.
Early and pronounced impairments were described as characteristic and thought
to underpin fluctuating cognition, although there have been few empirical
studies in this area. The complex array of neuropsychiatric, motor, and cognitive
deficits and the extreme sensitivity reactions to neuroleptic drugs experienced
by DLB patients raise a number of vital treatment issues that can only be
managed optimally with accurate diagnostic assignment.7
In most studies examining the clinical criteria for the operationalized diagnosis
of DLB, the specificity of diagnosis has been high, but sensitivity has been
poor.8 There have been a paucity of studies
examining the neuropsychological profile of DLB and the contribution of neuropsychological
evaluation to the diagnostic workup. Expert opinion has highlighted attentional
deficits as a key area in DLB,7 although the
empirical evidence base is small.
Hansen et al1 compared 9 patients with
DLB with 9 patients with AD. More severe deficits of attentional function
(digit span subtest from the Wechsler Adult Intelligence Scale–Revised)
were seen in DLB. Sahgal et al9 reported that
DLB patients had significantly greater impairment on a computerized delayed
matching-to-sample task. Ayre et al10, 11
used the Cognitive Drug Research Computerized Assessment System for Dementia
Patients (COGDRAS-D) computerized test battery12
to compare attention in 46 patients with AD and 24 patients with DLB. The
DLB group performed significantly worse on simple reaction time (SRT) and
choice reaction time (CRT) tasks and digit vigilance (VIG) compared with the
AD group.
The overall pattern is consistent, with DLB patients showing significantly
greater impairment on a range of attentional tasks. However, each of these
studies is modest in size, none including more than 24 patients with DLB,
and few had verified accuracy of clinical diagnosis. A larger study, from
a cohort with confirmed diagnostic accuracy, is required to confirm the pattern
of attentional deficits in DLB.
Fluctuating cognition occurs in all the major dementias and is characterized
by periodic shifts in the level of arousal, ranging from episodes of lucidity
to reduced awareness and even stupor. Fluctuating cognition occurs in 80%
to 90% of patients with DLB13, 14
and in 20% of patients with AD.15, 16
Prevalence rates of 30% to 50% are also reported in vascular dementia.17, 18 Consistent with expert opinion, Walker
et al19 identified a significant association
between fluctuating cognition and fluctuating attention, both of which were
significantly more severe in DLB than AD patients.
We investigated the hypothesis that attention and fluctuating attention
are significantly more impaired in DLB than AD patients in a large representative
patient sample, with confirmed diagnostic accuracy.
SUBJECTS AND METHODS
The study sample consists of 155 dementia subjects (85 with DLB, 80
with AD) and 35 elderly controls. Patients were recruited from a dementia
case register of consecutive referrals to old age psychiatry services in Tyneside,
England, with spouses of patients recruited as healthy elderly volunteers.
Good diagnostic accuracy has been achieved for the first 50 patients undergoing
postmortem examination from the sample of 338 individuals within the overall
case register (DLB: sensitivity, 0.83; specificity, 0.91; AD: sensitivity,
0.87; specificity, 0.8320). Patients with dementia
were matched for the severity of cognitive impairment using the Mini-Mental
State Examination (MMSE).21 All patients were
assessed with a structured psychiatric history (history and etiology schedule22), a standardized physical examination that incorporated
the modified Unified Parkinson's Disease Rating Scale (M-UPDRS),23
and a validated instrument to evaluate symptoms of depression (Cornell Depression
Scale,24 which in conjunction with questions
regarding impact and duration of symptoms was used to diagnose major depression
according to Diagnostic and Statistical Manual of Mental
Disorders, Revised Third Edition25 criteria).
Dementia with Lewy bodies was diagnosed according to the internationally agreed
consensus criteria7 and AD was diagnosed according
to National Institute of Neurological and Communicative Disorders and Stroke–Alzheimer's
Disease and Related Disorders Association criteria.26
The Joint Ethics Committee of Newcastle and North Tyneside Health Authority
University of Newcastle Upon Tyne granted ethical approval. Following full
explanation and discussion of the study, patients and healthy volunteers gave
their consent to the test, with additional assent from the next of kin for
all cognitively impaired patients.
NEUROPSYCHOLOGICAL EVALUATIONS OF ATTENTION AND FLUCTUATING ATTENTION
Subjects were assessed using the COGDRAS-D.12
Attentional tasks included the following: SRT (20 trials), each time "yes"
was presented in the center of the screen, the participant was required to
press the "yes" button as quickly as possible; CRT (30 trials), each time
"yes" or "no" was presented in the center of the screen, the participant was
required to press the corresponding "yes" or "no" button as quickly as possible
(accuracy and reaction time measures were derived); cognitive reaction time
(CogRT), calculated by subtracting the SRT from the CRT; VIG (90 trials),
a digit was displayed constantly on the right-hand side of the screen (VIGRT)
and 90 digits were serially presented (80 min-1) in the middle
of the screen; participants were required to press "yes" every time that digit
matched the digit constantly displayed on the right side of the screen.
Within-trial variability (SD in the attentional measures of CRT) and
an overall measure of attentional variability (CRT SD x VIGRT SD) were
assessed in single trials, all lasting approximately 90 seconds.
STATISTICAL ANALYSIS
The mean scores and the measures of variability on the attentional tasks
were compared between DLB and AD patients and between both dementia groups
and controls using the independent sample t test.
The same evaluation was completed separately to compare DLB and AD patients
with MMSE scores greater than 20 to provide additional information regarding
differences in attentional performance and processing speed in patients with
mild dementia. The pattern of change in attentional performance with increasing
cognitive impairment is described and evaluated with pairwise correlations
using the Pearson multivariate correlation coefficient (R). All of these evaluations were completed for the overall group and
separately, excluding patients who did not attain 50% accuracy on the respective
CRT or VIG tasks. Both parkinsonism and depression were considered to be potentially
important confounders. The correlation between the M-UPDRS score and each
of the attentional measures was evaluated using Pearson multivariate correlation
coefficient, and patients with and without major depression were compared
using the 2-sample t test. Data were analyzed using
the SPSS computer software program.27
RESULTS
One hundred fifty-five patients (85 with DLB: 40% female; mean ±
SD age, 78.0 ± 6.3 years; mean ± SD MMSE score, 17.3 ±
4.6; 80 with AD: 55% female; mean ± SD age, 79.3 ± 6.8 years;
mean ± SD MMSE score, 17.3 ± 4.6) and 35 elderly controls (71%
female; mean ± SD age, 73.9 ± 7.4 years; mean ± SD MMSE
score, 28.3 ± 1.2) were assessed.
The DLB patients were significantly more impaired than the AD patients
on all tests of attention and fluctuating attention. In a repeat analysis
excluding patients with less than 50% accuracy on the respective CRT or VIG
tasks, differences between the VIGRT of patients with the 2 dementias disappeared,
but the DLB patients were more impaired on all of the other tasks (Table 1). Both dementia groups were significantly
more impaired on SRT, CRT, VIG, and all measures of attentional variability
than the elderly controls. Cognitive reaction time was, however, significantly
more impaired in DLB patients than controls, but was not significantly more
impaired in those with AD than the control group (Table 1), indicating that impairment of CogRT was specific to DLB.
|
|
|
|
Table 1. Attention and Variability in Attention: Comparison of DLB
and AD*
|
|
|
The M-UPDRS score was inversely correlated with VIG accuracy (R = -0.26, P = .04), but
there were no significant correlations with any of the other parameters (SRT R = 0.16, P = .22, SRT SD R = 0.16, P = .21, VIGRT R = 0.24, P = .06, VIG SD R = 0.08, P = .55, CRT accuracy R = -0.14, P = .28, CRT R = 0.19, P = .13, CRT SD R = 0.16, P = .22, CogRT R = 0.11, P = .45). Major depression
was not significantly associated with any of the measures (SRT t = 0.4, P = .70, SRT SD t = 0.6, P = .58, VIG accuracy t = 0.1, P = .92, VIGRT t = 0.3, P = .79, VIG SD t = 0.6, P = .53, CRT accuracy t = 0.7, P = .47, CRT t = 0.5, P = .64, CRT SD t = 0.5, P = 0.67, CogRT t = 0.1, P = .93).
In both DLB and AD, most measures of attentional performance and most
indices of fluctuating attention were significantly correlated to the MMSE
score. This effect was still apparent on CRT tasks among DLB patients when
excluding the group with poor accuracy (<50%), although it was attenuated
to some extent for CRT variability in AD patients with good levels of accuracy
(Table 2). In both DLB (R = 0.21, P = .11) and AD (R = 0.13, P = .29), however, there
were no significant correlations between MMSE and CogRT.
|
|
|
|
Table 2. Correlations Between Specific Measures of Attention and Processing
Speed and Mini-Mental State Examination Score*
|
|
|
The severity and fluctuation of attentional impairments are particularly
pronounced in DLB patients with MMSE scores of 10 or less, even excluding
patients with poor levels of accuracy (<50%). It should, however, be noted
that the differences between DLB patients with MMSE scores greater than 20
and AD patients with MMSE scores of 10 or less were rather modest for most
categories of symptoms. Cognitive reaction time was similar in AD patients
with MMSE scores of more than 10 and controls, but became more comparable
to DLB values in the patients with the lowest MMSE scores (Figure 1 and Figure 2).
Statistical comparisons between the DLB (n = 15) and AD (n = 15) patients
with MMSE scores greater than 20 indicated significant differences in VIG
accuracy (t = 2.4, P = .02),
CRT (t = 2.4, P = .02),
and CRT variability (t = 2.6, P = 0.01) despite the small sample size.
|
|
|
|
Figure 1. Reaction times (in milliseconds):
relationship with severity of cognitive impairment. MMSE indicates Mini-Mental
State Examination; SEV.GA, severe dementia (MMSE score <10) with good accuracy
(>50%); DLB, dementia with Lewy bodies; and AD, Alzheimer disease. For DLB
patients, n = 84 (MMSE scores <11, n = 8; MMSE score of 11-20, n = 61;
MMSE score >20, n = 15); for AD patients, n = 75 (MMSE scores <11, n =
6; MMSE score of 11-20, n = 54; MMSE score >20, n = 15); and for control patients,
n = 35.
|
|
|
|
|
|
|
Figure 2. Choice reaction time, accuracy,
and vigilance accuracy. MMSE indicates Mini-Mental State Examination; DLB,
dementia with Lewy bodies; and AD, Alzheimer disease. For DLB patients, n
= 84 (MMSE scores <11, n = 8; MMSE score of 11-20, n = 61; MMSE score >20,
n = 15); for AD patients, n = 75 (MMSE scores <11, n = 6; MMSE score of
11-20, n = 54; MMSE score >20, n = 15); and for control patients, n = 35.
|
|
|
COMMENT
The present study confirms that attentional deficits and fluctuations
in attention are substantially more severe in DLB patients than in those with
AD, even excluding patients with poor levels of accuracy, and that both dementia
groups have greater overall attentional impairments than elderly controls.
A number of other factors, such as parkinsonism with slowed motor speed, depression,
or general slowing of cognitive processing speed, could theoretically have
contributed to these findings. The data evaluation did not, however, indicate
that either motor speed or mood was a major confounder. The general slowing
of reaction times could certainly imply a slowing of cognitive processing,
although the broad deficits CRT and VIG accuracy and reaction times indicate
a more widespread impairment of attentional processing.
Cognitive reaction time was the only attentional measure that was impaired
in DLB patients compared with controls, but it did not differ significantly
between controls and AD patients. Cognitive reaction time is a means of studying
the information processing requirements while controlling for perceptuomotor
dysfunction. Our findings indicate the possibility that slowed "central processing
speed" is a specific neuropsychological feature of DLB, which is not apparent
in AD patients with MMSE scores of more than 10. Between-group differences
may have been underestimated, since the marked increase of SRT in DLB patients
with severe dementia may have skewed the calculation of CogRT in some patients.
The pattern of change of variability in SRT and CRT tasks with increasing
severity of dementia also indicated important differences between the 2 dementias.
Variability in reaction time increased dramatically with increased cognitive
impairment in the DLB patients, but remained fairly static at all levels of
impairment in the patients with AD. This supports the hypothesis that fluctuating
attention is characteristic of DLB.7
In the present study, a standardized computerized battery of attentional
tasks was successfully completed by the study participants, who included a
number of people with MMSE scores below 10; however, within this more impaired
group care needs to be taken when interpreting the information from patients
with poor levels of accuracy. This battery can be completed in 15 minutes
and appears highly suitable for use in clinical practice. In addition, it
clearly has sufficient sensitivity to distinguish among different dementia
groups, even in mildly impaired patients. The highly significant differences
in attentional performance between DLB and AD patients suggest that detailed
neuropsychology could provide an important component of the diagnostic workup,
although the significant correlation between attentional performance and overall
MMSE score emphasize the need to interpret the results within the context
of the overall severity of cognitive impairment for most attentional measures.
This relationship diminished to some extent in AD patients when those with
poor levels of accuracy were excluded, except for CRT, which remained significantly
correlated to MMSE score. Even focusing on DLB patients with good levels of
accuracy, a strong relationship to MMSE scores was evident. The exception
was CogRT, which was independent of dementia severity in both dementia groups.
This finding is difficult to explain and may again be an artifact of the marked
increase in SRTs in patients with more severe dementia. The results are also
important in emphasizing that fluctuations in attention are common among patients
with moderate-to-severe AD.
Both neuropsychological and clinical observations strongly suggest that
DLB patients experience great difficulty in sustaining attention. The key
role of the cholinergic system in attention,28, 29, 30
fluctuating cognition (particularly attention), and disturbances of consciousness19 has been well documented.31
The results of the present study support this hypothesis, with attentional
deficits arising in mild cases of DLB, where marked cholinergic loss is an
early feature,32 but not occurring until a
much more advanced stage of the AD, where severe cholinergic deficits are
a late feature.33
Now that sensitive and practical tests are available, further work using
specific receptor ligands in in vivo neuroimaging studies, detailed clinicopathological
and cliniconeurochemical correlations, and pharmacological challenge can pinpoint
more accurately the chemical systems of brain areas that are involved in different
aspects of attentional performance. Clearly, the role of cholinesterase inhibitors
will be important to investigate in this regard.
CONCLUSIONS
Overall, slowed processing speed, attentional impairments, and fluctuation
in attentional impairments are significantly more severe in DLB than AD patients.
However, in both disease groups, deficits of attention become more pronounced
with increasing severity of the dementia and hence need to be interpreted
within the context of overall cognitive deficits. If interpreted in this way,
a more detailed evaluation of attention can make an important contribution
to the diagnostic assessment. Perhaps most important, however, deficits of
CogRT were specific to DLB patients and were not associated with global cognitive
performance and hence should form a core component of the neuropsychological
evaluation of these cases. It is also evident that fluctuations in cognition
are common in moderate-to-severe AD.
AUTHOR INFORMATION
Accepted for publication November 1, 2000.
From the Institute for the Health of the Elderly, Wolfson Research
Centre, Newcastle General Hospital (Drs Ballard, O'Brien, Rowan, and McKeith),
and Department of Psychology, University of Newcastle Upon Tyne (Mr Gray,
Ms Cormack, and Dr Tovee), Newcastle, England; CDR Limited, Reading, England
(Dr Ayre); Bensham Hospital, Gateshead, England (Dr Thompson); Blackberry
Hill Hospital, Bristol, England (Dr Bucks); and Harvard University, Boston,
Mass (Dr Walker).
Corresponding author and reprints: Clive Ballard, MRCPsych, MD, Institute
for the Health of the Elderly, Wolfson Research Centre, Newcastle General
Hospital, Westgate Road, Newcastle, England NE4 6BE (e-mail: c.g.ballard{at}ncl.ac.uk).
REFERENCES
| |
1. Hansen L, Salmon D, Galasko D, et al. The Lewy body variant of Alzheimer's disease: a clinical and pathological
entity. Neurology. 1990;40:1-8.
FREE FULL TEXT
2. Perry RH, Irving D, Blessed G, Fairbairn A, Perry EK. A clinically and pathologically distinct form of Lewy body dementia
in the elderly. J Neurol Sci. 1990;95:119-139.
FULL TEXT
|
ISI
| PUBMED
3. Dickson DW, Ruan D, Crystal H, et al. Hippocampal degeneration differentiates diffuse Lewy body disease (DLBD)
from Alzheimer's disease: light and electron microscopic immunocytochemistry
of CA2-3 neurites specific to DLBD. Neurology. 1991;41:1402-1409.
FREE FULL TEXT
4. Ballard CG, Mohan RNC, Patel A, Bannister C. Idiopathic clouding of consciousness: do the patients have cortical
Lewy body disease? Int J Geriatr Psychiatry. 1993;8:571-576.
FULL TEXT
|
ISI
5. Ballard CG, Saad K, Patel A, et al. The prevalence and phenomenology of psychotic symptoms in dementia
sufferers. Int J Geriatr Psychiatry. 1995;10:477-486.
FULL TEXT
|
ISI
6. Shergill S, Mullen E, D'Ath P, Katona C. What is the clinical prevalence of Lewy body dementia? Int J Psychiatry. 1994;9:907-912.
FULL TEXT
|
ISI
7. McKeith IG, Galasko D, Kosaka K, et al. Consensus guidelines for the clinical and pathologic diagnosis of dementia
with Lewy bodies (DLB): report of the Consortium on DLB International Workshop. Neurology. 1996;47:1113-1124.
FREE FULL TEXT
8. McKeith IG, O'Brien J, Ballard C. Diagnosing dementia with Lewy bodies. Lancet. 1999;354:1227-1228.
FULL TEXT
|
ISI
| PUBMED
9. Sahgal A, Galloway PH, McKeith IG, Edwardson JA, Lloyd S. A comparative study of attentional deficits in senile dementias of
Alzheimer and Lewy body types. Dementia. 1992;3:350-354.
10. Ayre G, Ballard C, Pincock C, McKeith I, Sahgal A, Wesnes K. Double dissociation between dementia with Lewy bodies and Alzheimer's
disease on tests of attentional and mnemonic function: the role of the basal
forebrain. J Psychopharmacol. 1998;A12(suppl):A64.
11. Ayre GA, Sahgal A, McKeith IG, et al. Distinct profiles of cognitive impairment in dementia with Lewy Bodies
and Alzheimer's disease. Neurology. In press.
12. Simpson PM, Surmon DJ, Wesnes KA, Wilcock GK. The Cognitive Drug Research Computerized Assessment System for Demented
Patients: a validation study. Int J Geriatr Psychiatry. 1991;6:95-102.
13. Byrne EJ, Lennox G, Lowe J, Godwin-Austen RB. Diffuse Lewy body disease: clinical features in 15 cases. J Neurol Neurosurg Psychiatry. 1989;52:709-717.
FREE FULL TEXT
14. McKeith IG, Perry RH, Fairbairn AF, Jabeen S, Perry EK. Operational criteria for senile dementia of Lewy body type (SDLT). Psychol Med. 1992;22:911-922.
ISI
| PUBMED
15. Kolbeinsson H, Jonsson A. Delirium and dementia in acute medical admissions of elderly patients
in Iceland. Acta Psychiatr Scand. 1993;87:123-127.
ISI
| PUBMED
16. Robertson B, Blennow K, Gottfries CG, Wallin A. Delirium in dementia. Int J Geriatr Psychiatry. 1998;13:49-56.
FULL TEXT
|
ISI
| PUBMED
17. Hachinski VC, Iliff LD, Zilhka E, et al. Cerebral blood flow in dementia. Arch Neurol. 1975;32:632-637.
FREE FULL TEXT
18. Roman GC, Tatemichi TK, Erkinjuntti T, et al. Vascular dementia: diagnostic criteria for research studies: report
of the NINDS-AIREN International Workshop. Neurology. 1993;43:250-260.
FREE FULL TEXT
19. Walker MP, Ayre GA, Wesnes K, McKeith IG, O'Brien JT, Ballard CG. Quantifying fluctuation in dementia with Lewy bodies, Alzheimer's disease,
and vascular dementia. Neurology. 2000;54:1616-1625.
FREE FULL TEXT
20. McKeith IG, Ballard CG, Perry RH, et al. Prospective validation of consensus criteria for the diagnosis of dementia
with Lewy bodies. Neurology. 2000;54:1050-1058.
FREE FULL TEXT
21. Folstein MF, Folstein SE, McHugh PR. "Mini-Mental State": a practical method for grading the cognitive state
of patients for the clinician. J Psychiatr Res. 1975;12:189-198.
FULL TEXT
|
ISI
| PUBMED
22. Dewey ME, Copeland JRM, Lobo A, Saz P, Dia J-L. Computerized diagnosis from a standardized history schedule: a preliminary
communication about the organic section of the HAS-AGECAT system. Int J Geriatr Psychiatry. 1992;7:443-446.
23. Fahn S, Elton R Unified Parkinson's Disease Rating Development Committee. Unified Parkinson's Disease Rating Scale. In: Fahn S, Marsden CD, Calne D, eds. Recent Developments
in Parkinson's Disease. Vol 2. New York, NY: Macmillan; 1987:153-163.
24. Alexopoulos GS, Abrams RC, Young RC, Shamoian CA. Cornell Scale for Depression in dementia. Biol Psychiatry. 1988;23:271-284.
FULL TEXT
|
ISI
| PUBMED
25. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders,
Revised Third Edition. Washington, DC: American Psychiatric Association; 1987.
26. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlen EM. Clinical Diagnosis of Alzheimer's Disease: report of the NINCDS-ADRDA
Work Group under the Auspices of Department of Health and Human Services Task
Forces on Alzheimer's Disease. Neurology. 1984;34:939-944.
FREE FULL TEXT
27. Statistical Package for the Social Sciences, Windows Version,
Release 5.0. Chicago, Ill: SPSS Inc; 1992.
28. Parrott AC. Transdermal scopolamine: a review of its effects upon motion sickness,
psychological performance, and physiological functioning. Aviat Space Environ Med. 1989;60:1-9.
PUBMED
29. Sunderland T, Tariot P, Murphy DL, Weingartner H, Mueller EA, Cohen RM. Scopolamine challenges in Alzheimer's disease. Psychopharmacology. 1985;87:247-249.
FULL TEXT
| PUBMED
30. Wesnes K, Warburton DM, Matz B. Effects of nicotine on stimulus sensitivity and response bias in a
visual vigilance task. Neuropsychobiology. 1983;9:41-44.
FULL TEXT
|
ISI
| PUBMED
31. Perry EK, Walker MP, Grace J, Perry R. Acetylcholine in mind: a neurotransmitter correlate of consciousness. Trends Neurosci. 1999;22:273-280.
FULL TEXT
|
ISI
| PUBMED
32. Perry EK, Smith CJ, Court JA, Perry RH. Cholinergic nicotinic and muscarinic receptors in dementia of Alzheimer,
Parkinson and Lewy body types. J Neural Transm Park Dis Dement Sect. 1990;2:149-158.
FULL TEXT
|
ISI
| PUBMED
33. Davis KL, Mohs RC, Marin D, et al. Cholinergic markers in elderly patients with early signs of Alzheimer
disease. JAMA. 1999;281:1401-1406.
FREE FULL TEXT
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati  Twitter
What's this?
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
|
Predisposing Factors Associated With Delirium Among Demented Long-Term Care Residents
Voyer et al.
Clin Nurs Res 2009;18:153-171.
ABSTRACT
Iron Accumulation in the Substantia Nigra of Patients With Alzheimer Disease and Parkinsonism
Brar et al.
Arch Neurol 2009;66:371-374.
ABSTRACT
| FULL TEXT
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 et al.
Brain 2008;131:690-705.
ABSTRACT
| FULL TEXT
Cognitive-Behavioral Profiles of Neurodegenerative Dementias: Beyond Alzheimer's Disease
Levy and Chelune
J Geriatr Psychiatry Neurol 2007;20:227-238.
ABSTRACT
Open angle glaucoma effects on preattentive visual search efficiency for flicker, motion displacement and orientation pop-out tasks
Loughman et al.
Br J Ophthalmol 2007;91:1493-1498.
ABSTRACT
| FULL TEXT
Visual recognition memory differentiates dementia with Lewy bodies and Parkinson's disease dementia
Mondon et al.
J. Neurol. Neurosurg. Psychiatry 2007;78:738-741.
ABSTRACT
| FULL TEXT
Higher cortical deficits influence attentional processing in dementia with Lewy bodies, relative to patients with dementia of the Alzheimer's type and controls
Bradshaw et al.
J. Neurol. Neurosurg. Psychiatry 2006;77:1129-1135.
ABSTRACT
| FULL TEXT
What best differentiates Lewy body from Alzheimer's disease in early-stage dementia?
Tiraboschi et al.
Brain 2006;129:729-735.
ABSTRACT
| FULL TEXT
Benefits of rivastigmine on attention in dementia associated with Parkinson disease
Wesnes et al.
Neurology 2005;65:1654-1656.
ABSTRACT
| FULL TEXT
Cognitive differences in dementia patients with autopsy-verified AD, Lewy body pathology, or both
Kraybill et al.
Neurology 2005;64:2069-2073.
ABSTRACT
| FULL TEXT
Fluctuations in cognition and alertness in Parkinson's disease and dementia
Serrano and Garcia-Borreguero
Neurology 2004;63:S31-S34.
ABSTRACT
| FULL TEXT
Fluctuating cognition in dementia with Lewy bodies and Alzheimer's disease is qualitatively distinct
Bradshaw et al.
J. Neurol. Neurosurg. Psychiatry 2004;75:382-387.
ABSTRACT
| FULL TEXT
DLB fluctuations: Specific features that reliably differentiate DLB from AD and normal aging
Ferman et al.
Neurology 2004;62:181-187.
ABSTRACT
| FULL TEXT
Dementia with Lewy Bodies: Neuropathology
Dickson
J Geriatr Psychiatry Neurol 2002;15:210-216.
ABSTRACT
|
