%0 Journal Article %J J Alzheimers Dis %D 2021 %T A Cost-Consequence Analysis of Different Screening Procedures in Alzheimer's Disease: Results from the MOPEAD Project. %A Wimo, Anders %A Belger, Mark %A Bon, Jaka %A Jessen, Frank %A Dumas, Annette %A Kramberger, Milica G %A Jamilis, Laura %A Johansson, Gunilla %A Rodrigo Salas, Adrián %A Rodríguez Gómez, Octavio %A Sannemann, Lena %A Stoekenbroek, Malou %A Gurruchaga Telleria, Miren %A Valero, Sergi %A Vermunt, Lisa %A Waterink, Lisa %A Winblad, Bengt %A Visser, Peter Jelle %A Zwan, Marissa %A Boada, Merce %X

BACKGROUND: For care planning and support, under-detection and late diagnosis of Alzheimer's disease (AD) is a great challenge. Models of Patient-Engagement for Alzheimer's Disease (MOPEAD) is an EU-funded project aiming at testing different strategies to improve this situation.

OBJECTIVE: To make a cost-consequence analysis of MOPEAD.

METHODS: Four screening strategies were tested in five countries (Germany, the Netherlands, Slovenia, Spain, and Sweden): 1) a web-approach; 2) Open-House initiative; 3) in primary care; and 4) by diabetes specialists. Persons-at-risk of AD in all strategies were offered referral to a hospital-based specialist. The primary health-economic outcome was the cost per true-positive case (TP) of AD from the screened population.

RESULTS: Of 2,847 screened persons, 1,121 screened positive (39%), 402 were evaluated at memory clinics (14%), and 236 got an AD diagnosis (8%). The cost per TP of those screened was 3,115€ with the web-approach, 2,722€ with the Open-House, 1,530€ in primary care, and 1,190€ by diabetes specialists. Sensitivity analyses that more likely reflect the real-world situation confirmed the results. The number-needed-to-screen was 30 with the web-approach, 8 with the Open-House and primary care, and 6 with the diabetes specialists.There were country differences in terms of screening rates, referrals to memory clinics, staff-types involved, and costs per TP.

CONCLUSION: In primary care and by the diabetes specialist, the costs per TP/screened population were lowest, but the capacity of such settings to identify cases with AD-risk must be discussed. Hence new diagnostic strategies such as web-solutions and Open-House initiatives may be valuable after modifications.

%B J Alzheimers Dis %V 83 %P 1149-1159 %8 2021 Sep 28 %G eng %N 3 %1 https://www.ncbi.nlm.nih.gov/pubmed/34420954?dopt=Abstract %R 10.3233/JAD-210303 %0 Journal Article %J J Alzheimers Dis %D 2021 %T The Relationship Between Cardiovascular Health and Rate of Cognitive Decline in Young-Old and Old-Old Adults: A Population-Based Study. %A Speh, Andreja %A Wang, Rui %A Winblad, Bengt %A Kramberger, Milica G %A Bäckman, Lars %A Qiu, Chengxuan %A Laukka, Erika J %X

BACKGROUND: Modifiable vascular risk factors have been associated with late-life cognitive impairment. The Life Simple 7 (LS7) score comprises seven cardiovascular health metrics: smoking, diet, physical activity, body mass index, plasma glucose, total serum cholesterol, and blood pressure.

OBJECTIVE: To investigate the association between individual and composite LS7 metrics and rate of cognitive decline, and potential differences in these associations between young-old and old-old individuals.

METHODS: This cohort study included 1,950 participants aged≥60 years (M = 70.7 years) from the Swedish National Study on Aging and Care-Kungsholmen (SNAC-K), who underwent repeated neuropsychological testing (episodic and semantic memory, verbal fluency, processing speed, global cognition) across 12 years. The LS7 score was assessed at baseline and categorized as poor, intermediate, or optimal. Level and change in cognitive performance as a function LS7 categories were estimated using linear mixed-effects models.

RESULTS: Having an optimal LS7 total score was associated with better performance (expressed in standard deviation units) at baseline for perceptual speed (β= 0.21, 95%CI 0.12-0.29), verbal fluency (β= 0.08, 0.00-0.16), and global cognition (β= 0.06, 0.00-0.12) compared to the poor group. Age-stratified analyses revealed associations for cognitive level and change only in the young-old (<  78 years) group. For the specific metrics, diverging patterns were observed for young-old and old-old individuals.

CONCLUSION: Meeting the LS7 criteria for ideal cardiovascular health in younger old age is associated with slower rate of cognitive decline. However, the LS7 criteria may have a different meaning for cognitive function in very old adults.

%B J Alzheimers Dis %V 84 %P 1523-1537 %8 2021 Dec 07 %G eng %N 4 %R 10.3233/JAD-210280 %0 Journal Article %J J Alzheimers Dis %D 2018 %T Treatment of Atrial Fibrillation in Patients with Dementia: A Cohort Study from the Swedish Dementia Registry. %A Subic, Ana %A Cermakova, Pavla %A Religa, Dorota %A Han, Shuang %A von Euler, Mia %A Kåreholt, Ingemar %A Johnell, Kristina %A Fastbom, Johan %A Bognandi, Liselia %A Winblad, Bengt %A Kramberger, Milica G %A Eriksdotter, Maria %A Garcia-Ptacek, Sara %K Aged %K Aged, 80 and over %K Anticoagulants %K Atrial Fibrillation %K Dementia %K Female %K Hemorrhage %K Humans %K Longitudinal Studies %K Male %K Registries %K Risk Factors %K Stroke %K Survival Analysis %K Sweden %K Warfarin %X

BACKGROUND: Patients with dementia might have higher risk for hemorrhagic complications with anticoagulant therapy prescribed for atrial fibrillation (AF).

OBJECTIVE: This study assesses the risks and benefits of warfarin, antiplatelets, and no treatment in patients with dementia and AF.

METHODS: Of 49,792 patients registered in the Swedish Dementia Registry 2007-2014, 8,096 (16%) had a previous diagnosis of AF. Cox proportional hazards models were used to calculate the risk for ischemic stroke (IS), nontraumatic intracranial hemorrhage, any-cause hemorrhage, and death.

RESULTS: Out of the 8,096 dementia patients with AF, 2,143 (26%) received warfarin treatment, 2,975 (37%) antiplatelet treatment, and 2,978 (37%) had no antithrombotic treatment at the time of dementia diagnosis. Patients on warfarin had fewer IS than those without treatment (5.2% versus 8.7%; p < 0.001) with no differences compared to antiplatelets. In adjusted analyses, warfarin was associated with a lower risk for IS (HR 0.76, CI 0.59-0.98), while antiplatelets were associated with increased risk (HR 1.25, CI 1.01-1.54) compared to no treatment. For any-cause hemorrhage, there was a higher risk with warfarin (HR 1.28, CI 1.03-1.59) compared to antiplatelets. Warfarin and antiplatelets were associated with a lower risk for death compared to no treatment.

CONCLUSIONS: Warfarin treatment in Swedish patients with dementia is associated with lower risk of IS and mortality, and a small increase in any-cause hemorrhage. This study supports the use of warfarin in appropriate cases in patients with dementia. The low percentage of patients on warfarin treatment indicates that further gains in stroke prevention are possible.

%B J Alzheimers Dis %V 61 %P 1119-1128 %8 2018 %G eng %N 3 %1 http://www.ncbi.nlm.nih.gov/pubmed/29286925?dopt=Abstract %R 10.3233/JAD-170575 %0 Journal Article %J J Alzheimers Dis %D 2017 %T Cost-Utility of Using Alzheimer's Disease Biomarkers in Cerebrospinal Fluid to Predict Progression from Mild Cognitive Impairment to Dementia. %A Handels, Ron L H %A Wimo, Anders %A Dodel, Richard %A Kramberger, Milica G %A Visser, Pieter Jelle %A Molinuevo, José Luis %A Verhey, Frans R J %A Winblad, Bengt %X

BACKGROUND: Diagnostic research criteria for Alzheimer's disease support the use of biomarkers in the cerebrospinal fluid (CSF) to improve the accuracy of the prognosis regarding progression to dementia for people with mild cognitive impairment (MCI).

OBJECTIVE: The aim of this study was to estimate the potential incremental cost-effectiveness ratio of adding CSF biomarker testing to the standard diagnostic workup to determine the prognosis for patients with MCI.

METHODS: In an early technology assessment, a mathematical simulation model was built, using available evidence on added prognostic value as well as expert opinion to estimate the incremental costs and quality-adjusted life years (QALYs) of 20,000 virtual MCI patients with (intervention strategy) and without (control strategy) relying on CSF, from a health-care sector perspective and with a 5-year time horizon.

RESULTS: Adding the CSF test improved the accuracy of prognosis by 11%. This resulted in an average QALY gain of 0.046 and € 432 additional costs per patient, representing an incremental cost-effectiveness ratio of € 9,416.

CONCLUSION: The results show the potential of CSF biomarkers in current practice from a health-economics perspective. This result was, however, marked by a high degree of uncertainty, and empirical research is required into the impact of a prognosis on worrying, false-positive/negative prognosis, and stigmatization.

%B J Alzheimers Dis %V 60 %P 1477-1487 %8 2017 %G eng %N 4 %1 http://www.ncbi.nlm.nih.gov/pubmed/29081416?dopt=Abstract %R 10.3233/JAD-170324 %0 Journal Article %J J Alzheimers Dis %D 2017 %T Long-Term Cognitive Decline in Dementia with Lewy Bodies in a Large Multicenter, International Cohort. %A Kramberger, Milica G %A Auestad, Bjørn %A Garcia-Ptacek, Sara %A Abdelnour, Carla %A Olmo, Josep Garre %A Walker, Zuzana %A Lemstra, Afina W %A Londos, Elisabet %A Blanc, Frédéric %A Bonanni, Laura %A McKeith, Ian %A Winblad, Bengt %A de Jong, Frank Jan %A Nobili, Flavio %A Stefanova, Elka %A Petrova, Maria %A Falup-Pecurariu, Cristian %A Rektorova, Irena %A Bostantjopoulou, Sevasti %A Biundo, Roberta %A Weintraub, Daniel %A Aarsland, Dag %K Aged %K Aged, 80 and over %K Analysis of Variance %K Cognition Disorders %K Cohort Studies %K Female %K Humans %K International Cooperation %K Lewy Body Disease %K Male %K Mental Status Schedule %K Middle Aged %X

BACKGROUND/OBJECTIVE: 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.

METHODS: 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.

RESULTS: 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 scan were included. Decline was not predicted by sex, baseline MMSE score, or presence of specific DLB core features.

CONCLUSIONS: The average annual decline in MMSE score in DLB is approximately two points. Although in the overall analyses there were no differences in the rate of decline between the three neurodegenerative disorders, there were indications of a more rapid decline in DLB than in AD and PDD. Further studies are needed to understand the predictors and mechanisms of cognitive decline in DLB.

%B J Alzheimers Dis %V 57 %P 787-795 %8 2017 %G eng %N 3 %1 http://www.ncbi.nlm.nih.gov/pubmed/28304294?dopt=Abstract %R 10.3233/JAD-161109 %0 Journal Article %J J Alzheimers Dis %D 2016 %T Cerebrospinal Fluid Alzheimer's Disease Biomarkers Across the Spectrum of Lewy Body Diseases: Results from a Large Multicenter Cohort. %A van Steenoven, Inger %A Aarsland, Dag %A Weintraub, Daniel %A Londos, Elisabet %A Blanc, Frédéric %A van der Flier, Wiesje M %A Teunissen, Charlotte E %A Mollenhauer, Brit %A Fladby, Tormod %A Kramberger, Milica G %A Bonanni, Laura %A Lemstra, Afina W %X

BACKGROUND: Concomitant Alzheimer's disease (AD) pathology is observed in Lewy body diseases (LBD), but the clinical impact is unknown. Only a few biomarker studies in LBD exist and have included small cohorts from single centers.

OBJECTIVE: We aimed to evaluate the prevalence of abnormal cerebrospinal fluid (CSF) AD biomarkers across the spectrum of LBD in a large multicenter cohort and to assess whether an AD biomarker profile was associated with demographic and clinical differences in dementia with Lewy bodies (DLB).

METHODS: We included 375 DLB patients, 164 Parkinson's disease (PD) patients without dementia, and 55 PD patients with dementia (PDD) from 10 centers. CSF amyloid-beta42 (Aβ42), total tau (t-tau), and phosphorylated tau (p-tau) values were dichotomized as abnormal or normal according to locally available cut-off values. A CSF AD profile was defined as abnormal Aβ42 combined with abnormal t-tau and/or p-tau.

RESULTS: A substantial proportion of DLB patients had abnormal values for CSF Aβ42, t-tau, and p-tau, while abnormal values were uncommon in PD without dementia. Patients with PDD had values in between. A CSF AD profile was observed in 25% of DLB patients, compared with only 9% of PDD and 3% of PD without dementia. Within DLB, patients with a CSF AD profile were older, more often female, performed worse on the Mini-Mental State Examination, and had shorter disease duration compared with patients with normal CSF.

CONCLUSION: A CSF AD profile is more common in DLB compared with PDD and PD, and is associated with more severe cognitive impairment in DLB.

%B J Alzheimers Dis %V 54 %P 287-95 %8 2016 Aug 18 %G eng %N 1 %1 http://www.ncbi.nlm.nih.gov/pubmed/27567832?dopt=Abstract %R 10.3233/JAD-160322 %0 Journal Article %J J Alzheimers Dis %D 2016 %T EEG Markers of Dementia with Lewy Bodies: A Multicenter Cohort Study. %A Bonanni, Laura %A Franciotti, Raffaella %A Nobili, Flavio %A Kramberger, Milica G %A Taylor, John-Paul %A Garcia-Ptacek, Sara %A Falasca, N Walter %A Famá, Francesco %A Cromarty, Ruth %A Onofrj, Marco %A Aarsland, Dag %X

Quantitative EEG (QEEG) has demonstrated good discriminative capacity for dementia with Lewy bodies (DLB) diagnosis as compared to Alzheimer's disease (AD) with a predictive value of 100% in a single cohort study. EEG in DLB was characterized by a dominant frequency (DF) in pre-alpha (5.5-7.5 Hz), theta, or delta bands and DF variability (DFV) >1.2 Hz, frequency prevalence (FP) pre-alpha in >40% and FP alpha in <32% of the epochs. To validate the aforementioned QEEG findings in independent cohorts of clinically diagnosed DLB versus AD patients, we analyzed EEG traces of 79 DLB and 133 AD patients (MMSE >20) collected from four European Centers. EEG traces from 19 scalp derivations were acquired as at least 10 min continuous signals and epoched in off-setting as series of 2-second-long epochs, subsequently processed by Fast Fourier Transform (frequency resolution 0.5 Hz). DLB patients showed EEG specific abnormalities in posterior derivations characterized by DF <8 Hz FP pre-alpha >50%, FP alpha <25%. DFV was >0.5 Hz. AD patients displayed stable alpha DF, DFV <0.5 Hz, FP pre-alpha <30%, and FP alpha >55%. DLB and AD differed for DF (p < 10-6), DFV (p < 0.05), FP pre-alpha (p < 10-12) and FP alpha (p < 10-12). Discriminant analysis detected specific cut-offs for every EEG mathematical descriptor; DF = 8, DFV = 2.2 Hz, FP pre-alpha=33%, FP alpha = 41% for posterior derivations. If at least one of the cut-off values was met, the percentage of DLB and AD patients correctly classified was 90% and 64%, respectively. The findings in this multicenter study support the validity of QEEG analysis as a tool for diagnosis in DLB patients.

%B J Alzheimers Dis %V 54 %P 1649-1657 %8 2016 Oct 18 %G eng %N 4 %1 http://www.ncbi.nlm.nih.gov/pubmed/27589528?dopt=Abstract %R 10.3233/JAD-160435