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1.  REM sleep behavior disorder preceding other aspects of synucleinopathies by up to half a century(e–Pub ahead of print)(CME) 
Neurology  2010;75(6):494-499.
Background:
Idiopathic REM sleep behavior disorder (RBD) may be the initial manifestation of synucleinopathies (Parkinson disease [PD], multiple system atrophy [MSA], or dementia with Lewy bodies [DLB]).
Methods:
We used the Mayo medical records linkage system to identify cases presenting from 2002 to 2006 meeting the criteria of idiopathic RBD at onset, plus at least 15 years between RBD and development of other neurodegenerative symptoms. All patients underwent evaluations by specialists in sleep medicine to confirm RBD, and behavioral neurology or movement disorders to confirm the subsequent neurodegenerative syndrome.
Results:
Clinical criteria were met by 27 patients who experienced isolated RBD for at least 15 years before evolving into PD, PD dementia (PDD), DLB, or MSA. The interval between RBD and subsequent neurologic syndrome ranged up to 50 years, with the median interval 25 years. At initial presentation, primary motor symptoms occurred in 13 patients: 9 with PD, 3 with PD and mild cognitive impairment (MCI), and 1 with PDD. Primary cognitive symptoms occurred in 13 patients: 10 with probable DLB and 3 with MCI. One patient presented with primary autonomic symptoms, diagnosed as MSA. At most recent follow-up, 63% of patients progressed to develop dementia (PDD or DLB). Concomitant autonomic dysfunction was confirmed in 74% of all patients.
Conclusions:
These cases illustrate that the α-synuclein pathogenic process may start decades before the first symptoms of PD, DLB, or MSA. A long-duration preclinical phase has important implications for epidemiologic studies and future interventions designed to slow or halt the neurodegenerative process.
GLOSSARY
= dementia with Lewy bodies;
= mild cognitive impairment;
= multiple system atrophy;
= Parkinson disease;
= PD with associated mild cognitive impairment;
= Parkinson disease dementia;
= polysomnogram;
= REM sleep behavior disorder.
doi:10.1212/WNL.0b013e3181ec7fac
PMCID: PMC2918473  PMID: 20668263
2.  Comparison of cognitive decline between dementia with Lewy bodies and Alzheimer's disease: a cohort study 
BMJ Open  2012;2(1):e000380.
Objectives
Dementia with Lewy bodies (DLB) accounts for 10%–15% of dementia cases at autopsy and has distinct clinical features associated with earlier institutionalisation and a higher level of carer distress than are seen in Alzheimer's disease (AD). At present, there is on-going debate as to whether DLB is associated with a more rapid cognitive decline than AD. An understanding of the rate of decline of cognitive and non-cognitive symptoms in DLB may help patients and carers to plan for the future.
Design
In this cohort study, the authors compared 100 AD and 58 DLB subjects at baseline and at 12-month follow-up on cognitive and neuropsychiatric measures.
Setting
Patients were recruited from 40 European centres.
Participants
Subjects with mild–moderate dementia. Diagnosis of DLB or AD required agreement between consensus panel clinical diagnosis and visual rating of 123I-FP-CIT (dopamine transporter) single photon emission computed tomography neuroimaging.
Outcome measures
The Cambridge Cognitive Examination including Mini-Mental State Examination and Neuropsychiatric Inventory (NPI).
Results
The AD and DLB groups did not differ at baseline in terms of age, gender, Clinical Dementia Rating score and use of cholinesterase inhibitors or memantine. NPI and NPI carer distress scores were statistically significantly higher for DLB subjects at baseline and at follow-up, and there were no differences between AD and DLB in cognitive scores at baseline or at follow-up. There was no significant difference in rate of progression of any of the variables analysed.
Conclusions
DLB subjects had more neuropsychiatric features at baseline and at follow-up than AD, but the authors did not find any statistically significant difference in rate of progression between the mild–moderate AD and DLB groups on cognitive or neuropsychiatric measures over a 12-month follow-up period.
Article summary
Article focus
Dementia with Lewy bodies (DLB) has distinct neuropsychiatric features.
At present, we do not know whether the poorer prognosis of DLB is due to a more rapid cognitive decline compared with Alzheimer's disease (AD).
Key messages
In this fairly large cohort of patients with DLB and AD, while there was no difference in level of cognitive impairment (Cambridge Cognitive Examination (CAMCOG) score) at baseline and at 12-month follow-up, DLB patients had significantly higher Neuropsychiatric Inventory (NPI) and NPI carer distress scores both at baseline and at 12-month follow-up.
Therefore, the worse prognosis of DLB is likely to be mediated by neuropsychiatric or other symptoms and not only by cognitive decline.
Strengths and limitations of this study
Inclusion of high number of subjects from 40 European clinical centres.
Well-characterised cases with both consensus panel clinical diagnosis (three clinical experts) and dopaminergic transporter single photon emission computed tomography imaging.
No autopsy data were available and therefore it is possible that more rapid cognitive decline may be present in pure DLB.
Only 1 year of follow-up.
There was higher attrition rate (no-follow-up assessment) in the DLB group, and DLB patients that did not return for follow-up were more impaired than AD patients.
doi:10.1136/bmjopen-2011-000380
PMCID: PMC3330257  PMID: 22318660
3.  Post mortem cerebrospinal fluid α-synuclein levels are raised in multiple system atrophy and distinguish this from the other α-synucleinopathies, Parkinson's disease and Dementia with Lewy bodies 
Neurobiology of Disease  2012;45(1):188-195.
Differentiating clinically between Parkinson's disease (PD) and the atypical parkinsonian syndromes of Progressive supranuclear palsy (PSP), corticobasal syndrome (CBS) and multiple system atrophy (MSA) is challenging but crucial for patient management and recruitment into clinical trials. Because PD (and the related disorder Dementia with Lewy bodies (DLB)) and MSA are characterised by the deposition of aggregated forms of α-synuclein protein (α-syn) in the brain, whereas CBS and PSP are tauopathies, we have developed immunoassays to detect levels of total and oligomeric forms of α-syn, and phosphorylated and phosphorylated oligomeric forms of α-syn, within body fluids, in an attempt to find a biomarker that will differentiate between these disorders. Levels of these 4 different forms of α-syn were measured in post mortem samples of ventricular cerebrospinal fluid (CSF) obtained from 76 patients with PD, DLB, PSP or MSA, and in 20 healthy controls. Mean CSF levels of total and oligomeric α-syn, and phosphorylated α-syn, did not vary significantly between the diagnostic groups, whereas mean CSF levels of phosphorylated oligomeric α-syn did differ significantly (p < 0.001) amongst the different diagnostic groups. Although all 4 measures of α-syn were higher in patients with MSA compared to all other diagnostic groups, these were only significantly raised (p < 0.001) in MSA compared to all other diagnostic groups, for phosphorylated oligomeric forms of α-syn. This suggests that this particular assay may have utility in differentiating MSA from control subject and patients with other α-synucleinopathies. However, it does not appear to be of help in distinguishing patients with PD and DLB from those with PSP or from control subjects. Western blots show that the principal form of α-syn within CSF is phosphorylated, and the finding that the phosphorylated oligomeric α-syn immunoassay appears to be the most informative of the 4 assays would be consistent with this observation.
doi:10.1016/j.nbd.2011.08.003
PMCID: PMC3657198  PMID: 21856424
Parkinson's disease; Dementia with Lewy Bodies; Multiple system atrophy; Alpha synuclein; Cerebrospinal fluid
4.  Imaging amyloid deposition in Lewy body diseases 
Neurology  2008;71(12):903-910.
Background:
Extrapyramidal motor symptoms precede dementia in Parkinson disease (PDD) by many years, whereas dementia occurs early in dementia with Lewy bodies (DLB). Despite this clinical distinction, the neuropsychological and neuropathologic features of these conditions overlap. In addition to widespread distribution of Lewy bodies, both diseases have variable burdens of neuritic plaques and neurofibrillary tangles characteristic of Alzheimer disease (AD).
Objectives:
To determine whether amyloid deposition, as assessed by PET imaging with the β-amyloid–binding compound Pittsburgh Compound B (PiB), can distinguish DLB from PDD, and to assess whether regional patterns of amyloid deposition correlate with specific motor or cognitive features.
Methods:
Eight DLB, 7 PDD, 11 Parkinson disease (PD), 15 AD, and 37 normal control (NC) subjects underwent PiB-PET imaging and neuropsychological assessment. Amyloid burden was quantified using the PiB distribution volume ratio.
Results:
Cortical amyloid burden was higher in the DLB group than in the PDD group, comparable to the AD group. Amyloid deposition in the PDD group was low, comparable to the PD and NC groups. Relative to global cortical retention, occipital PiB retention was lower in the AD group than in the other groups. For the DLB, PDD, and PD groups, amyloid deposition in the parietal (lateral and precuneus)/posterior cingulate region was related to visuospatial impairment. Striatal PiB retention in the DLB and PDD groups was associated with less impaired motor function.
Conclusions:
Global cortical amyloid burden is high in dementia with Lewy bodies (DLB) but low in Parkinson disease dementia. These data suggest that β-amyloid may contribute selectively to the cognitive impairment of DLB and may contribute to the timing of dementia relative to the motor signs of parkinsonism.
GLOSSARY
= Automated Anatomic Labeling;
= Alzheimer disease;
= Alzheimer’s Disease Research Center;
= American version of the National Adult Reading Test;
= analysis of covariance;
= Blessed Dementia Scale;
= cerebral amyloid angiopathy;
= Clinical Dementia Rating;
= Clinical Dementia Rating Sum of Boxes;
= dementia with Lewy bodies;
= distribution volume ratio;
= Cued Selective Reminding Test;
= Free Selective Reminding Test;
= Hoehn and Yahr;
= Massachusetts General Hospital;
= Mini-Mental State Examination;
= normal control;
= neurofibrillary tangle;
= Neuropsychiatric Inventory Questionnaire;
= not significant;
= Parkinson disease;
= Parkinson disease dementia;
= Pittsburgh Compound B;
= region of interest;
= Statistical Parametric Mapping;
= UK Parkinson’s Disease Society Brain Bank Research Center;
= United Parkinson’s Disease Rating Scale;
= Wechsler Adult Intelligence Scale–Revised.
doi:10.1212/01.wnl.0000326146.60732.d6
PMCID: PMC2637553  PMID: 18794492
5.  Performance on the dementia rating scale in Parkinson's disease with dementia and dementia with Lewy bodies: comparison with progressive supranuclear palsy and Alzheimer's disease 
Background: The relation between dementia with Lewy bodies (DLB) and Parkinson's disease with dementia (PDD) is unknown.
Objectives: To compare the cognitive profiles of patients with DLB and PDD, and compare those with the performance of patients with a subcortical dementia (progressive supranuclear palsy) and a cortical dementia (Alzheimer's disease).
Design: Survey of cognitive features.
Setting: General community in Rogaland county, Norway, and a university dementia and movement disorder research centre in the USA.
Patients: 60 patients with DLB, 35 with PDD, 49 with progressive supranuclear palsy, and 29 with Alzheimer's disease, diagnosed by either standardised clinical procedures and criteria (all PDD and Alzheimer cases and 76% of cases of progressive supranuclear palsy), or necropsy (all DLB cases and 24% of cases of progressive supranuclear palsy). Level of dementia severity was matched using the total score on the dementia rating scale adjusted for age and education.
Main outcome measures: Dementia rating scale subscores corrected for age.
Results: No significant differences between the dementia rating scale subscores in the PDD and DLB groups were found in the severely demented patients; in patients with mild to moderate dementia the conceptualisation subscore was higher in PDD than in DLB (p = 0.03). Compared with Alzheimer's disease, PDD and DLB had higher memory subscores (p < 0.001) but lower initiation and perseveration (p = 0.008 and p=0.021) and construction subscores (p = 0.009 and p = 0.001). DLB patients had a lower conceptualisation subscore (p = 0.004). Compared with progressive supranuclear palsy, PDD and DLB patients had lower memory subscores (p < 0.001).
Conclusions: The cognitive profiles of patients with DLB and PDD were similar, but they differed from those of patients with Alzheimer's disease and progressive supranuclear palsy. The cognitive pattern in DLB and PDD probably reflects the superimposition of subcortical deficits upon deficits typically associated with Alzheimer's disease.
doi:10.1136/jnnp.74.9.1215
PMCID: PMC1738667  PMID: 12933921
6.  Fluoxetine Ameliorates Behavioral and Neuropathological Deficits in a Transgenic Model Mouse of α-synucleinopathy 
Experimental neurology  2012;234(2):405-416.
The term α-synucleinopathies refers to a group of age-related neurological disorders including Parkinson’s disease (PD), Dementia with Lewy Bodies (DLB) and Multiple System Atrophy (MSA) that display an abnormal accumulation of alpha-synuclein (α-syn). In contrast to the neuronal α-syn accumulation observed in PD and DLB, MSA is characterized by a widespread oligodendrocytic α-syn accumulation. Transgenic mice expressing human α-syn under the oligodendrocyte-specific myelin basic protein promoter (MBP1-hαsyn tg mice) model many of the behavioral and neuropathological alterations observed in MSA.
Fluoxetine, a selective serotonin reuptake inhibitor, has been shown to be protective in toxin-induced models of PD, however its effects in an in vivo transgenic model of α-synucleinopathy remain unclear. In this context, this study examined the effect of fluoxetine in the MBP1-hαsyn tg mice, a model of MSA.
Fluoxetine adminstration ameliorated motor deficits in the MBP1-hαsyn tg mice, with a concomitant decrease in neurodegenerative pathology in the basal ganglia, neocortex and hippocampus. Fluoxetine adminstration also increased levels of the neurotrophic factors, GDNF (glial-derived neurotrophic factor) and BDNF (brain-derived neurotrophic factor) in the MBP1-hαsyn tg mice compared to vehicle-treated tg mice. This fluoxetine-induced increase in GDNF and BDNF protein levels was accompanied by activation of the ERK signaling pathway. The effects of fluoxetine adminstration on myelin and serotonin markers were also examined.
Collectively these results indicate that fluoxetine may represent a novel therapeutic intervention for MSA and other neurodegenerative disorders.
doi:10.1016/j.expneurol.2012.01.008
PMCID: PMC3897235  PMID: 22281106
7.  Higher cortical deficits influence attentional processing in dementia with Lewy bodies, relative to patients with dementia of the Alzheimer's type and controls 
Background
Attentional dysfunction is believed to be a prominent and distinguishing neuropsychological feature of dementia with Lewy bodies (DLB); yet, the specific nature of the attentional deficit and factors that can potentially influence attentional processing in DLB have not been fully defined.
Aims
To clarify the nature of the attentional deficit in early‐stage DLB relative to patients with early‐stage dementia of the Alzheimer's type (DAT) and elderly controls, and examine the effect of task complexity and type of cognitive load on attentional processing in DLB.
Methods
Attentional impairment and fluctuating attention were investigated in three groups of subjects—patients with clinical features of early probable DLB (n = 20), a group with early probable DAT (n = 19) and healthy elderly controls (n = 20)—using an experimental computerised reaction time paradigm.
Results
Patients with DLB showed greater attentional impairment and fluctuations in attention relative to patients with DAT and elderly controls. The attentional deficit was generalised in nature but increased in magnitude as greater demands were placed on attentional selectivity. Attentional deficits in DLB were most pronounced under task conditions that required more active recruitment of executive control and visuospatial cognitive processes.
Conclusions
Attentional deficits in DLB are widespread and encompass all aspects of attentional function. Deficits in higher cortical function influence the degree of attentional impairment and fluctuating attention, suggesting that attentional processing in DLB is mediated by interacting cortical and subcortical mechanisms. These findings serve to clarify the nature of the attentional deficit in DLB and have potentially important ramifications for our understanding of the neurocognitive underpinnings of fluctuations.
doi:10.1136/jnnp.2006.090183
PMCID: PMC2077555  PMID: 16772356
8.  Longitudinal assessment of global and regional atrophy rates in Alzheimer's disease and dementia with Lewy bodies 
NeuroImage : Clinical  2015;7:456-462.
Background & objective
Percent whole brain volume change (PBVC) measured from serial MRI scans is widely accepted as a sensitive marker of disease progression in Alzheimer's disease (AD). However, the utility of PBVC in the differential diagnosis of dementia remains to be established. We compared PBVC in AD and dementia with Lewy bodies (DLB), and investigated associations with clinical measures.
Methods
72 participants (14 DLBs, 25 ADs, and 33 healthy controls (HCs)) underwent clinical assessment and 3 Tesla T1-weighted MRI at baseline and repeated at 12 months. We used FSL-SIENA to estimate PBVC for each subject. Voxelwise analyses and ANCOVA compared PBVC between DLB and AD, while correlational tests examined associations of PBVC with clinical measures.
Results
AD had significantly greater atrophy over 1 year (1.8%) compared to DLB (1.0%; p = 0.01) and HC (0.9%; p < 0.01) in widespread regions of the brain including periventricular areas. PBVC was not significantly different between DLB and HC (p = 0.95). There were no differences in cognitive decline between DLB and AD. In the combined dementia group (AD and DLB), younger age was associated with higher atrophy rates (r = 0.49, p < 0.01).
Conclusions
AD showed a faster rate of global brain atrophy compared to DLB, which had similar rates of atrophy to HC. Among dementia subjects, younger age was associated with accelerated atrophy, reflecting more aggressive disease in younger people. PBVC could aid in differentiating between DLB and AD, however its utility as an outcome marker in DLB is limited.
Highlights
•AD showed faster global and regional brain atrophy in comparison to DLB.•Similar rates of global and regional atrophy were found in DLB and HC.•Longitudinal imaging could improve clinical differentiation of DLB from AD.•Atrophy rates might not be a useful marker to track disease progression in DLB.
doi:10.1016/j.nicl.2015.01.017
PMCID: PMC4325088
Dementia; Alzheimer's disease; Lewy bodies; Neuroimaging; Atrophy
9.  Dopamine cell loss in the periaqueductal gray in multiple system atrophy and Lewy body dementia 
Neurology  2009;73(2):106-112.
Background:
Experimental studies indicate that dopaminergic neurons in the ventral periaqueductal gray matter (PAG) are involved in maintenance of wakefulness. Excessive daytime sleepiness (EDS) is a common manifestation of multiple system atrophy (MSA) and dementia with Lewy bodies (DLB) but involvement of these neurons has not yet been explored.
Methods:
We sought to determine whether there is loss of dopaminergic neurons in the ventral PAG in MSA and DLB. We studied the midbrain obtained at autopsy from 12 patients (9 male, 3 female, age 61 ± 3) with neuropathologically confirmed MSA, 12 patients (11 male, 1 female, age 79 ± 4) with diagnosis of DLB and limbic or neocortical Lewy body disease, and 12 controls (7 male, 5 female, ages 67 ± 4). Fifty-micron sections were immunostained for tyrosine hydroxylase (TH) or α-synuclein and costained with thionin. Cell counts were performed every 400 μm throughout the ventral PAG using stereologic techniques.
Results:
Compared to the total estimated cell numbers in controls (21,488 ± 8,324 cells), there was marked loss of TH neurons in the ventral PAG in both MSA (11,727 ± 5,984; p < 0.01) and DLB (5,163 ± 1,926; p < 0.001) cases. Cell loss was more marked in DLB than in MSA. There were characteristic α-synuclein inclusions in the ventral PAG in both MSA and DLB.
Conclusions:
There is loss of putative wake-active ventral periaqueductal gray matter dopaminergic neurons in both multiple system atrophy and dementia with Lewy bodies, which may contribute to excessive daytime sleepiness in these conditions.
GLOSSARY
= Alzheimer disease;
= Braak and Braak;
= Consortium to Establish a Registry for Alzheimer's Disease;
= continuous positive airway pressure;
= dementia with Lewy bodies;
= electrocardiogram;
= excessive daytime sleepiness;
= electrooculography;
= Epworth Sleepiness Scale;
= glial cytoplasmic inclusion;
= Lewy body disease;
= multiple system atrophy;
= MSA with predominant parkinsonism;
= MSA with predominant cerebellar involvement;
= obstructive sleep apnea;
= periaqueductal gray matter;
= polysomnogram;
= REM sleep behavior disorder;
= tyrosine hydroxylase.
doi:10.1212/WNL.0b013e3181ad53e7
PMCID: PMC2713188  PMID: 19597132
10.  Magnetic Resonance Spectroscopy in the Diagnosis of Dementia with Lewy Bodies 
BioMed Research International  2014;2014:809503.
Dementia with Lewy bodies (DLB) is considered to be the second most frequent primary degenerative dementing illness after Alzheimer's disease (AD). DLB, together with Parkinson's disease (PD), Parkinson's disease with dementia (PDD) belong to α-synucleinopathies—a group of neurodegenerative diseases associated with pathological accumulation of the α-synuclein protein. Dementia due to PD and DLB shares clinical symptoms and neuropsychological profiles. Moreover, the core features and additional clinical signs and symptoms for these two very similar diseases are largely the same. Neuroimaging seems to be a promising method in differential diagnosis of dementia studies. The development of imaging methods or other objective measures to supplement clinical criteria for DLB is needed and a method which would accurately facilitate diagnosis of DLB prior to death is still being searched. Proton magnetic resonance spectroscopy (1H-MRS) provides a noninvasive method of assessing an in vivo biochemistry of brain tissue. This review summarizes the main results obtained from the application of neuroimaging techniques in DLB cases focusing on 1H-MRS.
doi:10.1155/2014/809503
PMCID: PMC4109391  PMID: 25110697
11.  Nonamnestic mild cognitive impairment progresses to dementia with Lewy bodies 
Neurology  2013;81(23):2032-2038.
Objective:
To determine the rate of progression of mild cognitive impairment (MCI) to dementia with Lewy bodies (DLB).
Methods:
We followed 337 patients with MCI in the Mayo Alzheimer's Disease Research Center (range 2–12 years). Competing risks survival models were used to examine the rates of progression to clinically probable DLB and Alzheimer disease (AD). A subset of patients underwent neuropathologic examination.
Results:
In this clinical cohort, 116 remained as MCI, while 49 progressed to probable DLB, 162 progressed to clinically probable AD, and 10 progressed to other dementias. Among nonamnestic MCI, progression rate to probable DLB was 20 events per 100 person-years and to probable AD was 1.6 per 100 person-years. Among amnestic MCI, progression rate to probable AD was 17 events per 100 person-years, and to DLB was 1.5 events per 100 person-years. In 88% of those who developed probable DLB, the baseline MCI diagnosis included attention and/or visuospatial deficits. Those who developed probable DLB were more likely to have baseline daytime sleepiness and subtle parkinsonism. In 99% of the clinically probable AD group, the baseline MCI diagnosis included memory impairment. Neuropathologic confirmation was obtained in 24 of 30 of those with clinically probable AD, and in 14 of 18 of those with clinically probable DLB.
Conclusion:
In a clinical sample, patients with nonamnestic MCI were more likely to develop DLB, and those with amnestic MCI were more likely to develop probable AD.
doi:10.1212/01.wnl.0000436942.55281.47
PMCID: PMC3854825  PMID: 24212390
12.  Striatal and extrastriatal dopamine transporter levels relate to cognition in Lewy body diseases: an 11C altropane positron emission tomography study 
Introduction
The biological basis of cognitive impairment in parkinsonian diseases is believed to be multifactorial. We investigated the contribution of dopamine deficiency to cognition in Parkinson disease (PD) and dementia with Lewy bodies (DLB) with dopamine transporter (DAT) imaging.
Methods
We acquired 11C altropane PET, magnetic resonance imaging and cognitive testing in 19 nondemented subjects with PD, 10 DLB and 17 healthy control subjects (HCS). We analyzed DAT concentration in putamen, caudate, anterior cingulate (AC), orbitofrontal and prefrontal regions, using the Standardized Uptake Volume Ratio with partial volume correction, and we related DAT concentration and global cortical thickness to neuropsychological performance.
Results
DAT concentration in putamen and in caudate were similar in PD and DLB groups and significantly lower than in HCS. Reduced caudate DAT concentration was associated with worse Clinical Dementia Rating Scale–sum of boxes (CDR-SB) scores and visuospatial skills in DLB but not in PD or HCS groups. Adjusting for putamen DAT concentration, as a measure of severity of motor disease, caudate DAT concentration was lower in DLB than in PD. Higher AC DAT concentration was associated with lower putamen DAT concentration in DLB and with higher putamen DAT concentration in PD. Higher AC DAT concentration in DLB correlated with greater impairment in semantic memory and language.
Conclusions
Caudate and AC dopamine dysfunction contribute in opposing directions to cognitive impairment in DLB.
Electronic supplementary material
The online version of this article (doi:10.1186/s13195-014-0052-7) contains supplementary material, which is available to authorized users.
doi:10.1186/s13195-014-0052-7
PMCID: PMC4245149  PMID: 25429309
13.  Demography, diagnostics, and medication in dementia with Lewy bodies and Parkinson’s disease with dementia: data from the Swedish Dementia Quality Registry (SveDem) 
Introduction
Whether dementia with Lewy bodies (DLB) and Parkinson’s disease with dementia (PDD) should be considered as one entity or two distinct conditions is a matter of controversy. The aim of this study was to compare the characteristics of DLB and PDD patients using data from the Swedish Dementia Quality Registry (SveDem).
Methods
SveDem is a national Web-based quality registry initiated to improve the quality of diagnostic workup, treatment, and care of patients with dementia across Sweden. Patients with newly diagnosed dementia of various types were registered in SveDem during the years 2007–2011. The current cross-sectional report is based on DLB (n = 487) and PDD (n = 297) patients. Demographic characteristics, diagnostic workup, Mini-Mental State Examination (MMSE) score, and medications were compared between DLB and PDD groups.
Results
No gender differences were observed between the two study groups (P = 0.706). PDD patients were significantly younger than DLB patients at the time of diagnosis (74.8 versus 76.8 years, respectively; P < 0.001). A significantly higher prevalence of patients with MMSE score ≤24 were found in the PDD group (75.2% versus 67.6%; P = 0.030). The mean number of performed diagnostic modalities was significantly higher in the DLB group (4.9 ± 1.7) than in the PDD group (4.1 ± 1.6; P < 0.001). DLB patients were more likely than PDD patients to be treated with cholinesterase inhibitors (odds ratio = 2.5, 95% confidence interval = 1.8–3.5), whereas the use of memantine, antidepressants, and antipsychotics did not differ between the groups.
Conclusion
This study demonstrates several differences in the dementia work-up between DLB and PDD. The onset of dementia was significantly earlier in PDD, while treatment with cholinesterase inhibitors was more common in DLB patients. Severe cognitive impairment (MMSE score ≤24) was more frequent in the PDD group, whereas more diagnostic tests were used to confirm a DLB diagnosis. Some similarities also were found, such as gender distribution and use of memantine, antidepressants, and antipsychotics drugs. Further follow-up cost-effectiveness studies are needed to provide more evidence for workup and treatment guidelines of DLB and PDD.
doi:10.2147/NDT.S45840
PMCID: PMC3700781  PMID: 23847419
dementia with Lewy bodies; Parkinson’s disease with dementia; age; diagnostic approach; medication; Mini-Mental State Examination
14.  Comparison of Clinical Manifestation in Familial Alzheimer's disease and Dementia with Lewy Bodies 
Archives of neurology  2008;65(12):1634-1639.
Background
The clinical delineation of Dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) remains unclear.
Objective
To compare the neuropsychological profiles of patients with clinically diagnosed Dementia with Lewy bodies (DLB) and Alzheimer's disease (AD).
Methods
We first compared measures of memory, orientation, language, executive, visual perception and visual construction function between persons with DLB and AD in two Caribbean Hispanic cohorts, including a family dataset (DLB =89; AD: n=118) and an epidemiologic dataset (DLB: n=70; AD: n=157). DLB in the family sample was further divided into i) families with two or more affected family members (DLB), or ii) one affected family member (DLB). To determine whether observed differences in cognitive profiles were driven by heritable factors, we then repeated the analyses in the epidemiologic cohort excluding all familial cases. We applied general linear models adjusting for age, sex, education, disease duration, and APOE-ε4 genotype.
Results
Persons with DLB were in both cohorts more severely impaired in orientation, visual construction and non verbal reasoning after controlling for potential confounders. Persons with 2 or more DLB cases per family had the most severe impairment in episodic and semantic memory, followed by those with one DLB case per family, then by those with AD. When familial AD and DLB cases were excluded from the analysis in the epidemiologic cohort, the differences between the AD and DLB groups persisted but were attenuated.
Conclusions
Compared to persons with AD, persons with DLB are more severely impaired in various cognitive domains, particularly orientation, visual perception and visual construction. The difference appears strong in familial rather than sporadic DLB. Whether this divergence in cognitive functions is caused by gene-gene or gene-environmental interactions remains unclear.
doi:10.1001/archneur.65.12.1634
PMCID: PMC2633487  PMID: 19064751
15.  Differential Diagnosis of Parkinsonism Using Dual-Phase F-18 FP-CIT PET Imaging 
Purpose
Dopamine transporter (DAT) imaging can demonstrate presynaptic dopaminergic neuronal loss in Parkinson’s disease (PD). However, differentiating atypical parkinsonism (APD) from PD is often difficult. We investigated the usefulness of dual-phase F-18 FP-CIT positron emission tomography (PET) imaging in the differential diagnosis of parkinsonism.
Methods
Ninety-eight subjects [five normal, seven drug-induced parkinsonism (DIP), five essential tremor (ET), 24 PD, 20 multiple system atrophy-parkinson type (MSA-P), 13 multiple system atrophy-cerebellar type (MSA-C), 13 progressive supranuclear palsy (PSP), and 11 dementia with Lewy bodies (DLB)] underwent F-18 FP-CIT PET. PET images were acquired at 5 min (early phase) and 3 h (late phase) after F-18 FP-CIT administration (185 MBq). Regional uptake pattern of cerebral and cerebellar hemispheres was assessed on early phase images and striatal DAT binding pattern was assessed on late phase images, using visual, quantitative, and statistical parametric mapping (SPM) analyses.
Results
Striatal DAT binding was normal in normal, ET, DIP, and MSA-C groups, but abnormal in PD, MSA-P, PSP, and DLB groups. No difference was found in regional uptake on early phase images among normal DAT binding groups, except in the MSA-C group. Abnormal DAT binding groups showed different regional uptake pattern on early phase images compared with PD in SPM analysis (FDR < 0.05). When discriminating APD from PD, visual interpretation of the early phase image showed high diagnostic sensitivity and specificity (75.4 % and 100 %, respectively). Regarding the ability to distinguish specific APD, sensitivities were 81 % for MSA-P, 77 % for MSA-C, 23 % for PSP, and 54.5 % for DLB.
Conclusions
Dual-phase F-18 FP-CIT PET imaging is useful in demonstrating striatal DAT loss in neurodegenerative parkinsonism, and also in differentiating APD, particularly MSA, from PD.
doi:10.1007/s13139-012-0182-4
PMCID: PMC4035208  PMID: 24895507
Atypical parkinsonism; Dual-phase; F-18 FP-CIT; Positron emission tomography; PET
16.  Autonomic Dysfunctions in Parkinsonian Disorders 
Journal of Movement Disorders  2009;2(2):72-77.
Background and Purpose:
Symptoms of autonomic dysfunctions are common in the patients with parkinsonian disorders. Because clinical features of autonomic dysfunctions are diverse, the comprehensive evaluation is essential for the appropriate management. For the appreciation of autonomic dysfunctions and the identification of differences, patients with degenerative parkinsonisms are evaluated using structured questionnaire for autonomic dysfunction (ADQ).
Methods:
Total 259 patients, including 192 patients with [idiopathic Parkinson’s disease (IPD, age 64.6 ± 9.6 years)], 37 with [multiple system atrophy (MSA, 62.8 ± 9.1)], 9 with [dementia with Lewy body (DLB, 73.9 ± 4.3)], and 21 with [progressive supranuclear palsy (PSP, 69.4 ± 9.6)]. The ADQ was structured for evaluation of the presence of symptoms and its severity due to autonomic dysfunction, covering gastrointestinal, urinary, sexual, cardiovascular and thermoregulatory domains. Patients were also evaluated for the orthostatic hypotension.
Results:
Although dementia with Lewy body (DLB) patients were oldest and duration of disease was longest in IPD, total ADQ scores of MSA and PSP (23.9 ± 12.6 and 21.1 ± 7.8) were significantly increased than that of IPD (15.1 ± 10.6). Urinary and cardiovascular symptom scores of MSA and gastrointestinal symptom score of PSP were significantly worse than those of IPD. The ratio of patient with orthostatic hypotension in IPD was 31.2% and not differed between groups (35.1% in MSA, 33.3% in DLB and 33.3% in PSP). But the systolic blood pressure dropped drastically after standing in patients with MSA and DLB than in patients with IPD and PSP.
Conclusions:
Patients with degenerative parkinsonism showed widespread symptoms of autonomic dysfunctions. The severity of those symptoms in patients with PSP were comparing to that of MSA patients and worse than that of IPD.
doi:10.14802/jmd.09019
PMCID: PMC4027718  PMID: 24868361
Parkinsonism; Autonomic dysfunction; Orthostatic hypotension
17.  Early Visuospatial Deficits Predict the Occurrence of Visual Hallucinations in Autopsy-Confirmed Dementia with Lewy Bodies 
Objectives
The current study explored the value of visuospatial findings for predicting the occurrence of visual hallucinations (VH) in a sample of patients with Dementia with Lewy bodies (DLB) compared to patients with Alzheimer’s disease (AD).
Participants/Measurements
Retrospective analysis of 55 autopsy-confirmed DLB and 55 demographically-similar, autopsy-confirmed AD cases determined whether severe initial visuospatial deficits on the WISC-R Block Design subtest predicted the development of VH. Visuospatial deficits were considered severe if Block Design z-scores were 2.5 or more standard deviations below the mean of a well-characterized normal control group (Severe-VIS; DLB: n=35, AD: n=26) and otherwise were considered mild (Mild-VIS; DLB: n=20, AD: n=29).
Results
Forty percent of the Severe-VIS DLB group had baseline VH compared to 0% of Mild-VIS DLB patients. Only 8% of the Severe-VIS and 3% Mild-VIS AD patients had baseline VH. During the follow-up period (mean=5.0 years), an additional 61% of the Severe-VIS but only 11% of the Mild-VIS DLB patients developed VH. In that period, 38% of the Severe-VIS and 20% of the Mild-VIS AD patients developed VH. After considering initial MMSE score and rate of decline, logistic regression analyses found that performance on Block Design significantly predicted the presence of VH in the DLB group but not the AD group.
Conclusions
The presence of early, severe deficits on neuropsychological tests of visuospatial skill increases the likelihood that patients with suspected DLB will develop the prototypical DLB syndrome. The presence of such deficits may identify those DLB patients whose syndrome is driven by alpha-synuclein pathology rather than AD pathology and may inform treatment plans as well as future research.
doi:10.1097/JGP.0b013e31823033bc
PMCID: PMC3260388  PMID: 21997600
Lewy body disease; Hallucinations, visual; Alzheimer’s disease; Visuospatial cognition
18.  PET imaging of amyloid with Florbetapir F 18 and PET imaging of dopamine degeneration with 18F-AV-133 (florbenazine) in patients with Alzheimer’s disease and Lewy body disorders 
BMC Neurology  2014;14:79.
Background
Biomarkers based on the underlying pathology of Alzheimer’s disease (AD) and Dementia with Lewy Bodies (DLB) have the potential to improve diagnosis and understanding of the substrate for cognitive impairment in these disorders. The objective of this study was to compare the patterns of amyloid and dopamine PET imaging in patients with AD, DLB and Parkinson’s disease (PD) using the amyloid imaging agent florbetapir F 18 and 18F-AV-133 (florbenazine), a marker for vesicular monamine type 2 transporters (VMAT2).
Methods
Patients with DLB and AD, Parkinson’s disease (PD) and healthy controls (HC) were recruited for this study. On separate days, subjects received intravenous injections of florbetapir, and florbenazine. Amyloid burden and VMAT2 density were assessed quantitatively and by binary clinical interpretation. Imaging results for both tracers were compared across the four individual diagnostic groups and for combined groups based on underlying pathology (AD/DLB vs. PD/HC for amyloid burden and PD/DLB vs. AD/HC for VMAT binding) and correlated with measures of cognition and parkinsonism.
Results
11 DLB, 10 AD, 5 PD, and 5 controls participated in the study. Amyloid binding was significantly higher in the combined AD/DLB patient group (n = 21) compared to the PD/HC groups (n = 10, mean SUVr: 1.42 vs. 1.07; p = 0.0006). VMAT2 density was significantly lower in the PD/DLB group (n = 16) compared to the AD/ HC group (n = 15; 1.83 vs. 2.97; p < 0.0001). Within the DLB group, there was a significant correlation between cognitive performance and striatal florbenazine binding (r = 0.73; p = 0.011).
Conclusions
The results of this study show significant differences in both florbetapir and florbenazine imaging that are consistent with expected pathology. In addition, VMAT density correlated significantly with cognitive impairment in DLB patients (ClinicalTrials.gov identifier: NCT00857506, registered March 5, 2009).
doi:10.1186/1471-2377-14-79
PMCID: PMC4027995  PMID: 24716655
PET imaging; Alzheimer’s disease; Parkinson’s disease; Biomarkers
19.  Imaging amyloid deposition in Lewy body diseases 
Neurology  2008;71(12):903-910.
Background
Extrapyramidal motor symptoms precede dementia in Parkinson disease (PDD) by many years, whereas dementia occurs early in dementia with Lewy bodies (DLB). Despite this clinical distinction, the neuropsychological and neuropathologic features of these conditions overlap. In addition to widespread distribution of Lewy bodies, both diseases have variable burdens of neuritic plaques and neurofibrillary tangles characteristic of Alzheimer disease (AD).
Objectives
To determine whether amyloid deposition, as assessed by PET imaging with the β-amyloid–binding compound Pittsburgh Compound B (PiB), can distinguish DLB from PDD, and to assess whether regional patterns of amyloid deposition correlate with specific motor or cognitive features.
Methods
Eight DLB, 7 PDD, 11 Parkinson disease (PD), 15 AD, and 37 normal control (NC) subjects underwent PiB-PET imaging and neuropsychological assessment. Amyloid burden was quantified using the PiB distribution volume ratio.
Results
Cortical amyloid burden was higher in the DLB group than in the PDD group, comparable to the AD group. Amyloid deposition in the PDD group was low, comparable to the PD and NC groups. Relative to global cortical retention, occipital PiB retention was lower in the AD group than in the other groups. For the DLB, PDD, and PD groups, amyloid deposition in the parietal (lateral and precuneus)/posterior cingulate region was related to visuospatial impairment. Striatal PiB retention in the DLB and PDD groups was associated with less impaired motor function.
Conclusions
Global cortical amyloid burden is high in dementia with Lewy bodies (DLB) but low in Parkinson disease dementia. These data suggest that β-amyloid may contribute selectively to the cognitive impairment of DLB and may contribute to the timing of dementia relative to the motor signs of parkinsonism.
doi:10.1212/01.wnl.0000326146.60732.d6
PMCID: PMC2637553  PMID: 18794492
20.  Cerebrospinal Fluid Biomarkers for Dementia with Lewy Bodies 
More than 750,000 of the UK population suffer from some form of cognitive impairment and dementia. Of these, 5–20% will have Dementia with Lewy Bodies (DLB). Clinico-pathological studies have shown that it is the low frequency of DLB clinical core features that makes the DLB diagnosis hardly recognisable during life, and easily misdiagnosed for other forms of dementia. This has an impact on the treatment and long-term care of the affected subjects. Having a biochemical test, based on quantification of a specific DLB biomarker within Cerebrospinal Fluid (CSF) could be an effective diagnostic method to improve the differential diagnosis. Although some of the investigated DLB CSF biomarkers are well within the clinical criteria for sensitivity and specificity (>90%), they all seem to be confounded by the contradictory data for each of the major groups of biomarkers (α-synuclein, tau and amyloid proteins). However, a combination of CSF measures appear to emerge, that may well be able to differentiate DLB from other dementias: α-synuclein reduction in early DLB, a correlation between CSF α-synuclein and Aβ42 measures (characteristic for DLB only), and t-tau and p-tau181 profile (differentiating AD from DLB).
doi:10.4061/2010/536538
PMCID: PMC2965495  PMID: 21048932
21.  Neuropsychiatric Features of Frontal Lobe Dysfunction in Autopsy-Confirmed Patients with Lewy Bodies and “Pure” Alzheimer’s Disease 
Objective
To compare patients with autopsy-confirmed Alzheimer’s disease (AD, #14) and Dementia with Lewy bodies (DLB) on the frequency of behaviors related to frontal systems dysfunction and the association of these behaviors with dementia severity.
Design
Cross-sectional survey of longitudinal cohort.
Setting
University Alzheimer’s disease research center.
Participants
Volunteer sample of 19 DLB and 38 AD participants with autopsy-confirmed diagnoses, similar in age (DLB: 77.3, AD: 77.5), education (15.2, 14.7), and Mini-Mental State Examination (MMSE) score (20.6, 20.5), with impairment ranging from mild deficits to moderate dementia.
Measurements
The Frontal Systems Behavior Scale (FrSBe)-Family Rating Form assessing patient apathy, disinhibition, and executive dysfunction by a knowledgeable informant.
Results
A two-way analysis of variance with the FrSBe total as the dependent variable revealed a significant MMSE by diagnosis interaction (F(1,53)=9.34, p=.004). Mean FrSBe total for AD patients showed significant impairment across the range of dementia severity, while it was relatively preserved for DLB patients in early stage of disease. The interaction term showed the same pattern for the executive dysfunction (F(1,53)=7.62, p=.008), disinhibition (F(1,53)=4.90, p=.031), and apathy (F(1,53)=9.77, p=.003) subscales.
Conclusions
While frontal behavioral symptoms in AD patients were present regardless of stage of dementia, DLB patients showed significant frontal dysfunction only in later stages. Results suggest that frontal subcortical circuits associated with behaviors assessed by the FrSBe are affected early in AD but not until later stages in DLB. Assessing specific behaviors related to frontal systems, coupled with stage of cognitive decline, may aid in clinical differentiation of AD and DLB.
doi:10.1016/j.jagp.2012.10.022
PMCID: PMC3664517  PMID: 23567425
Dementia with Lewy bodies; Alzheimer’s disease; Frontal systems; Behavioral symptoms
22.  Selective Molecular Alterations in the Autophagy Pathway in Patients with Lewy Body Disease and in Models of α-Synucleinopathy 
PLoS ONE  2010;5(2):e9313.
Background
Lewy body disease is a heterogeneous group of neurodegenerative disorders characterized by α-synuclein accumulation that includes dementia with Lewy bodies (DLB) and Parkinson's Disease (PD). Recent evidence suggests that impairment of lysosomal pathways (i.e. autophagy) involved in α-synuclein clearance might play an important role. For this reason, we sought to examine the expression levels of members of the autophagy pathway in brains of patients with DLB and Alzheimer's Disease (AD) and in α-synuclein transgenic mice.
Methodology/Principal Findings
By immunoblot analysis, compared to controls and AD, in DLB cases levels of mTor were elevated and Atg7 were reduced. Levels of other components of the autophagy pathway such as Atg5, Atg10, Atg12 and Beclin-1 were not different in DLB compared to controls. In DLB brains, mTor was more abundant in neurons displaying α-synuclein accumulation. These neurons also showed abnormal expression of lysosomal markers such as LC3, and ultrastructural analysis revealed the presence of abundant and abnormal autophagosomes. Similar alterations were observed in the brains of α-synuclein transgenic mice. Intra-cerebral infusion of rapamycin, an inhibitor of mTor, or injection of a lentiviral vector expressing Atg7 resulted in reduced accumulation of α-synuclein in transgenic mice and amelioration of associated neurodegenerative alterations.
Conclusions/Significance
This study supports the notion that defects in the autophagy pathway and more specifically in mTor and Atg7 are associated with neurodegeneration in DLB cases and α-synuclein transgenic models and supports the possibility that modulators of the autophagy pathway might have potential therapeutic effects.
doi:10.1371/journal.pone.0009313
PMCID: PMC2824828  PMID: 20174468
23.  Risk factors for dementia with Lewy bodies 
Neurology  2013;81(9):833-840.
Objective:
To determine the risk factors associated with dementia with Lewy bodies (DLB).
Methods:
We identified 147 subjects with DLB and sampled 2 sex- and age-matched cognitively normal control subjects for each case. We also identified an unmatched comparison group of 236 subjects with Alzheimer disease (AD). We evaluated 19 candidate risk factors in the study cohort.
Results:
Compared with controls, subjects with DLB were more likely to have a history of anxiety (odds ratio; 95% confidence interval) (7.4; 3.5–16; p < 0.0001), depression (6.0; 3.7–9.5; p < 0.0001), stroke (2.8; 1.3–6.3; p = 0.01), a family history of Parkinson disease (PD) (4.6; 2.5–8.6; p < 0.0001), and carry APOE ε4 alleles (2.2; 1.5–3.3; p < 0.0001), but less likely to have had cancer (0.44; 0.27–0.70; p = 0.0006) or use caffeine (0.29; 0.14–0.57; p < 0.0001) with a similar trend for alcohol (0.65; 0.42–1.0; p = 0.0501). Compared with subjects with AD, subjects with DLB were younger (72.5 vs 74.9 years, p = 0.021) and more likely to be male (odds ratio; 95% confidence interval) (5.3; 3.3–8.5; p < 0.0001), have a history of depression (4.3; 2.4–7.5; p < 0.0001), be more educated (2.5; 1.1–5.6; p = 0.031), have a positive family history of PD (5.0; 2.4–10; p < 0.0001), have no APOE ε4 alleles (0.61; 0.40–0.93; p = 0.02), and to have had an oophorectomy before age 45 years (7.6; 1.5–39; p = 0.015).
Conclusion:
DLB risk factors are an amalgam of those for AD and PD. Smoking and education, which have opposing risk effects on AD and PD, are not risk factors for DLB; however, depression and low caffeine intake, both risk factors for AD and PD, increase risk of DLB more strongly than in either.
doi:10.1212/WNL.0b013e3182a2cbd1
PMCID: PMC3908463  PMID: 23892702
24.  Neurodegenerative Disorder Risk in Idiopathic REM Sleep Behavior Disorder: Study in 174 Patients 
PLoS ONE  2014;9(2):e89741.
Objective
To estimate the risk for developing a defined neurodegenerative syndrome in a large cohort of idiopathic REM sleep behavior disorder (IRBD) patients with long follow-up.
Methods
Using the Kaplan-Meier method, we estimated the disease-free survival rate from defined neurodegenerative syndromes in all the consecutive IRBD patients diagnosed and followed-up in our tertiary referal sleep center between November 1991 and July 2013.
Results
The cohort comprises 174 patients with a median age at diagnosis of IRBD of 69 years and a median follow-up of four years. The risk of a defined neurodegenerative syndrome from the time of IRBD diagnosis was 33.1% at five years, 75.7% at ten years, and 90.9% at 14 years. The median conversion time was 7.5 years. Emerging diagnoses (37.4%) were dementia with Lewy bodies (DLB) in 29 subjects, Parkinson disease (PD) in 22, multiple system atrophy (MSA) in two, and mild cognitive impairment (MCI) in 12. In six cases, in whom postmortem was performed, neuropathological examination disclosed neuronal loss and widespread Lewy-type pathology in the brain in each case.
Conclusions
In a large IRBD cohort diagnosed in a tertiary referal sleep center, prolonged follow-up indicated that the majority of patients are eventually diagnosed with the synucleinopathies PD, DLB and less frequently MSA. IRBD represented the prodromal period of these conditions. Our findings in IRBD have important implications in clinical practice, in the investigation of the early pathological events occurring in the synucleinopathies, and for the design of interventions with potential disease-modifying agents.
doi:10.1371/journal.pone.0089741
PMCID: PMC3935943  PMID: 24587002
25.  Comorbidity profile in dementia with Lewy bodies versus Alzheimer’s disease: a linkage study between the Swedish Dementia Registry and the Swedish National Patient Registry 
Introduction
Compared to Alzheimer’s disease (AD), dementia with Lewy bodies (DLB) is usually associated with a more complex clinical picture and higher burden of care. Yet, few investigations have been performed on comorbidities and risk factors of DLB. Therefore, we aimed to compare clinical risk factors and comorbidity profile in DLB and AD patients using two nationwide registries.
Methods
This is a linkage study between the Swedish dementia registry (SveDem) and the Swedish National Patient Registry conducted on 634 subjects with DLB and 9161 individuals with AD registered during the years 2007–2012. Comorbidity profile has been coded according to the International Classification of Diseases version 10 (ICD 10) in addition to the date of each event. The main chapters of the ICD-10, the Charlson score of comorbidities and a selected number of neuropsychiatric diseases were compared between the DLB and AD groups. Comorbidity was registered before and after the dementia diagnosis.
Results
“Mental and behavioral disorders”, “diseases of the nervous system”, “diseases of the eye and adnexa”, diseases of the “circulatory”, “respiratory”, and “genitourinary” systems, “diseases of the skin and subcutaneous tissue” and “diseases of the musculoskeletal system and connective tissue” occurred more frequently in the DLB group after multivariate adjustment. Depression [adjusted OR = 2.12 (95%CI 1.49 to 3.03)] and migraine [adjusted OR = 3.65 (95%CI 1.48 to 9.0)] were more commonly recorded before the diagnosis of dementia in the DLB group. Following dementia diagnosis, ischemic stroke [adjusted OR = 1.89 (95%CI 1.21 to 2.96)] was more likely to happen among the DLB patients compared to the AD population.
Conclusions
Our study indicated a worse comorbidity profile in DLB patients with higher occurrence of depression, stroke and migraine compared with the AD group. Deeper knowledge about the underlying mechanisms of these associations is needed to explore possible reasons for the different pattern of comorbidity profile in DLB compared to AD and their prognostic significance.
doi:10.1186/s13195-014-0065-2
PMCID: PMC4255539  PMID: 25478027

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