No Significant Difference in Cognitive Decline and Mortality between Parkinson’s Disease Dementia and Dementia with Lewy Bodies: Naturalistic Longitudinal Data from the Swedish Dementia Registry (original) (raw)
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Parkinson's Disease Dementia and Lewy Body Disease
2019
Dementia with Lewy Bodies (DLB) and Parkinson's disease dementia (PD-D) are Lewy body (LB)-related neurodegen-erative dementias sharing many clinical and neuropatholo-gical features. Both conditions affect cognition, behavior, movement, and autonomic functions. When the clinical picture is fully developed, DLB and PD-D are practically indistinguishable. Regarding molecular pathology, both are synucleinopathies, characterized by the accumulation of misfolded α-synuclein protein in the form of LBs and Lewy neurites. DLB and PD-D are believed to represent two entities on the same disease spectrum. The main difference between these two conditions is the temporal sequence of symptoms. Motor symptoms precede dementia in PD-D, whereas it coincides with or follows dementia in DLB within 1 year. Dementia with Lewy Bodies DLB is the second most common neurodegenerative dementia following Alzheimer's disease (AD). In contrast to AD, motor and behavioral symptoms appear early in the course of the disease in DLB and may be the major burden of the disease. Epidemiology and Risk Factors DLB accounts for 5% of all dementia cases over the age of 75. 1 In a systematic review, the prevalence of DLB was found to be between 0.02 and 33.3 per 1,000. 1 The incidence rate of DLB is 3.5 per 100,000 person-years overall, 2 and the incidence increases with age. 3 Risk factors associated with DLB are old age, mutations in the glucocerebrosidase (GBA) and α-synuclein genes, and carrying the H1 haplotype of the microtubule-associated protein tau (MAPT). 4-6 There are also new candidate risk genes associated with DLB such as BCL7C and GABRB3. 7 Compared with AD, the findings on apolipoprotein E4 (APOE) polymorphisms in DLB are inconclusive. Vascular risk factors are less associated with DLB compared with AD. Clinical Features The cardinal clinical features of DLB consist of motor, cog-nitive, behavioral, and autonomic symptoms. The cognitive profile is characterized by particularly severe deficits in attention as well as executive and visuospatial functions. In early phases of the disease, memory may be relatively Keywords ► dementia with Lewy bodies ► Parkinson's disease dementia ► synucleinopathy ► imaging Abstract Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PD-D) are Lewy body-related neurodegenerative disorders sharing common clinical and neuropathological findings. The clinical features of both conditions include cognitive impairment, behavioral symptoms, autonomic dysfunction, sleep disorders, and parkinsonism. The cognitive profile of both disorders is characterized by particularly severe deficits in executive and visuospatial functions as well as attention. Clinical differentiation between DLB and PD-D is based on an arbitrary distinction between the time of onset of parkinsonism and cognitive symptoms; extrapyramidal symptoms precede dementia in PD-D, whereas it coincides with or follows dementia within 1 year in DLB. When the clinical picture is fully developed, DLB and PD-D are practically indistinguishable. Although the diagnosis is basically clinical, structural and functional neuroimaging as well as cerebrospinal fluid biomarkers may help the clinician in the diagnosis. Placebo-controlled randomized trials of the cholinesterase inhibitors have shown modest but significant benefits in cognition, global function, and neuropsychiatric symptoms in both disorders. Behavioral symptoms such as hallucinations and delusions should be treated with caution with antipsychotics, as they have the potential to worsen motor and cognitive symptoms.
Neuropsychiatric Disease and Treatment, 2013
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 costeffectiveness studies are needed to provide more evidence for workup and treatment guidelines of DLB and PDD.
Pathologic Correlates of Dementia in Individuals with Lewy Body Disease
Brain Pathology, 2010
Cognitive impairment and dementia are more common in patients with Parkinson disease (PD) than age-matched controls, and appear to become more frequent as PD progresses. However, estimates of dementia in patients with PD have varied widely, likely due in part to differences in case definition, case ascertainment, and methodology. First, we review investigations of usual pathologic correlates of dementia in patients with brainstem (b) Lewy Body Disease (LBD) and report our findings from the initial 266 brain autopsies from a population-based study of brain aging and incident dementia. Our results showed that 2.6% of subjects were diagnosed with PD during life but that 20% had bLBD at autopsy. Seventy percent of individuals with bLBD had high-level of one or more cerebral pathologic changes significantly associated with dementia: Alzheimer's disease (AD), cerebral (c) LBD, or microvascular brain injury (μVBI); these were commonly co-morbid. Next we consider proposed contributors to cognitive impairment and dementia in the approximately 30% of patients with only bLBD, including regionally selective dendritic degeneration of neostriatal medium spiny neurons. Diseases contributing to cognitive impairment and dementia in patients with bLBD are heterogeneous, providing diagnostic challenges as well as multiple opportunities for successful intervention in patients with PD.
Neuropathology and Applied Neurobiology, 2020
Novel clinicopathological characteristics differentiate dementia with Lewy bodies from Parkinson's disease dementia Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) known as Lewy body dementias have overlapping clinical and neuropathological features. Neuropathology in both includes combination of Lewy body and Alzheimer's disease (AD) pathology. Cerebral amyloid angiopathy (CAA), often seen in AD, is increasingly recognized for its association with dementia. Aims: This study investigated clinical and neuropathological differences between DLB and PDD. Methods: 52 PDD and 16 DLB cases from the Queen Square Brain Bank (QSBB) for Neurological disorders were included. Comprehensive clinical data of motor and cognitive features were obtained from medical records. Neuropathological assessment included examination of CAA, Lewy body and AD pathology. Results: CAA was more common in DLB than in PDD (P = 0.003). The severity of CAA was greater in DLB than in PDD (P = 0.009), with significantly higher CAA scores in the parietal lobe (P = 0.043), and the occipital lobe (P = 0.008), in DLB than in PDD. The highest CAA scores were observed in cases with APOE e4/4 and e2/4. Survival analysis showed worse prognosis in DLB, as DLB reached each clinical milestone sooner than PDD. Absence of dyskinesia in DLB is linked to the significantly lower lifetime cumulative dose of levodopa in comparison with PDD. Conclusions: This is the first study which identified prominent concurrent CAA pathology as a pathological substrate of DLB. More prominent CAA and rapid disease progression as measured by clinical milestones distinguish DLB from PDD.
Parkinson’s Disease and Dementia: A Longitudinal Study (DEMPARK)
Neuroepidemiology, 2011
Background: Parkinson’s disease (PD) is a progressive neurodegenerative motor disorder. However, non-motor complications frequently alter the course of the disease. A particularly disabling non-motor symptom is dementia. Methods/Design: The study is designed as a multicentre prospective, observational cohort study of about 700 PD patients aged 45–80 years with or without dementia and PD-mild cognitive impairment (MCI). The patients will be recruited in eight specialized movement disorder clinics and will be followed for 36 months. Information about the patients’ functional status will be assessed at baseline and 6-/12- month intervals. In addition, 120 patients with dementia with Lewy bodies (DLB) will be included. Well-established standardized questionnaires/tests will be applied for detailed neuropsychological assessment. In addition, patients will be asked to participate in modules including volumetric MRI, genetic parameters, and neuropsychology to detect risk factors, early dia...
Dementia with Lewy bodies: findings from an international multicentre study
International Journal of Geriatric Psychiatry, 2000
Objectives[ To describe the baseline demographic\ neuropsychiatric and neurological data of a large selected clinical sample of patients with dementia with Lewy Bodies "DLB# from an international multicentre trial with rivastigmine[ To examine the usefulness of the Consensus Criteria for the diagnosis of DLB in di}erent countries[ Methods[ Seventeen centres from Spain\ the UK and Italy recruited patients diagnosed clinically as probable DLB according to recent Consensus Criteria "McKeith et al[\ 0885#[ A standard clinical protocol including inclu! sion:exclusion criteria\ collection of demographic and medical data\ cognitive "Mini Mental State Examination] MMSE#\ motor "Uni_ed Parkinson|s Disease Rating Scale] UPDRS# and neuropsychiatric "Neuropsychiatric Inven! tory] NPI# examinations\ was applied after obtaining informed consent[ Data were summarised and compared across countries with uni! and multivariate analyses[ Results[ One hundred and twenty patients were recruited] 45[6) males\ mean "SD# age 62[8 "5[3# years\ range 46Ð 76 years[ Sixty percent ful_lled all three core diagnostic features of DLB\ and 39) only two "{parkinsonism| 81[3)\ {cognitive~uctuations| 78[0)\ {visual hallucinations| 66[2)#[ {Systematised delusions| "35)# and {repeated falls| "31)# were the most frequent supportive diagnostic features[ There were no di}erences across countries in demo! graphic\ diagnostic or clinical features[ Patients showed a wide range of psychopathology which was weakly correlated with cognitive impairment[ Some mild extrapyramidal signs "EPS# were observed in most patients[ Conclusions[ The Consensus Criteria for DLB can be consistently applied across many di}erent sites for multicentre studies[ {Parkinsonism| and {cognitive~uctuations| as core features and {systematised delusions| and {repeated falls| as supportive features are the most frequent diagnostic clues[ Neuropsychiatric disturbances\ in particular apathy\ delusions\ hallucinations and anxiety\ and mild symmetric EPS are frequent in DLB and are only related weakly to cognitive impairment[
Journal of Alzheimer's disease : JAD, 2017
The aim of this study was to describe the rate and clinical predictors of cognitive decline in dementia with Lewy bodies (DLB), and compare the findings with Alzheimer's disease (AD) and Parkinson's disease dementia (PDD) patients. Longitudinal scores for the Mini-Mental State Examination (MMSE) in 1,290 patients (835 DLB, 198 PDD, and 257 AD) were available from 18 centers with up to three years longitudinal data. Linear mixed effects analyses with appropriate covariates were used to model MMSE decline over time. Several subgroup analyses were performed, defined by anti-dementia medication use, baseline MMSE score, and DLB core features. The mean annual decline in MMSE score was 2.1 points in DLB, compared to 1.6 in AD (p = 0.07 compared to DLB) and 1.8 in PDD (p = 0.19). Rates of decline were significantly higher in DLB compared to AD and PDD when baseline MMSE score was included as a covariate, and when only those DLB patients with an abnormal dopamine transporter SPECT s...
Journal of Alzheimer's disease : JAD, 2016
Limited data compares clinical profiles of Lewy Body Dementia (LBD) with Alzheimer's disease (AD) and Parkinson's disease (PD). Twenty-one mildly demented ambulatory LBD subjects were individually matched by MMSE score with 21 AD subjects and by UPDRS motor score with 21 PD subjects. Matched by age, gender, education, and race, pairs were compared using cognitive, functional, behavioral, and motor measures. LBD group performed worse than PD on axial motor, gait, and balance measures. AD had more amnesia and orientation impairments, but less executive and visuospatial deficits than LBD subjects. LBD group had more sleepiness, cognitive/behavioral fluctuations, hallucinations, and sleep apnea than AD or PD. Axial motor, gait, and balance disturbances correlated with executive, visuospatial, and global cognition deficits. LBD is differentiated from AD and PD by retrieval memory, visuospatial, and executive deficits; axial motor, gait and balance impairments; sleepiness, cogniti...
Lewy Body Dementias: A Coin with Two Sides?
Behavioral Sciences
Lewy body dementias (LBDs) consist of dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD), which are clinically similar syndromes that share neuropathological findings with widespread cortical Lewy body deposition, often with a variable degree of concomitant Alzheimer pathology. The objective of this article is to provide an overview of the neuropathological and clinical features, current diagnostic criteria, biomarkers, and management of LBD. Literature research was performed using the PubMed database, and the most pertinent articles were read and are discussed in this paper. The diagnostic criteria for DLB have recently been updated, with the addition of indicative and supportive biomarker information. The time interval of dementia onset relative to parkinsonism remains the major distinction between DLB and PDD, underpinning controversy about whether they are the same illness in a different spectrum of the disease or two separate neurodegenerative disorders. The...