Cognitive decline in dementia with Lewy bodies: a 5-year prospective cohort study

OBJECTIVES: We report the cognitive decline in persons diagnosed with mild dementia with Lewy bodies (DLB) and mild Alzheimer's disease (AD) during 5 years of annual follow-ups. METHODS: Patients were recruited into the study from geriatric, psychiatric and neurology clinics in Western Norway during 2005–2013. They were diagnosed according to clinical consensus criteria, based on standardised clinical rating scales. Autopsy-based diagnoses were available for 20 cases. Cognitive decline for up to 5 years was assessed using the Clinical Dementia Rating (CDR) scale and the Mini-Mental State Examination (MMSE). Survival analysis including Cox regression (time to reach severe dementia) and linear mixed-effects (lme) modelling were used to model the decline on MMSE. RESULTS: At least one follow-up assessment was available for 67 patients with DLB and 107 patients with AD, with a median follow-up time of 4.3 years. The time to reach severe dementia was significantly shorter in DLB (median 1793 days) compared with AD (1947 days; p=0.033), and the difference remained significant in the multiple Cox regression analysis (HR=2.0, p<0.02). In the adjusted lme model, MMSE decline was faster in DLB (annual decline 4.4 points) compared with AD (3.2 points; p<0.008). CONCLUSIONS: Our findings show that from the mild dementia stage, patients with DLB have a more rapid cognitive decline than in AD. Such prognostic information is vital for patients and families and crucial for planning clinical trials and enabling health economic modelling

Polypharmacy is associated with functional decline in Alzheimer's disease and Lewy body dementia

Antecedentes: en la demencia, varios factores pueden influir en el deterioro funcional además de la cognición. En Este estudio, nuestro objetivo es estudiar la posible asociación del número de medicamentos prescritos con funcional trayectorias de declive durante un seguimiento de cinco años en personas diagnosticadas con enfermedad de Alzheimer leve (EA) o Demencia con cuerpos de Lewy (LBD). Métodos: Este es un análisis longitudinal de un estudio de cohorte noruego titulado "El estudio de la demencia de occidente Noruega". Se incluyeron 196 pacientes con diagnóstico reciente de EA (n = 111) y LBD (n = 85), seguidos anualmente durante 5 años. Realizamos modelos lineales de efectos mixtos para analizar la asociación del número de medicamentos con declive funcional medido por la Escala Rápida de Calificación de Discapacidad - 2. Resultados: La media de medicamentos prescritos al inicio del estudio fue 4,18∓2,60, para AD 3,92∓2,51 y LBD 4,52∓2,70. El número de medicamentos aumentó durante el seguimiento; en el quinto año, la media de EA fue de 7,28∓4,42 y para LBD 8.11∓5.16. El uso de más medicamentos se asoció con un deterioro funcional más rápido en la EA (Est. 0.04, SE0.01, valor p 0.003) y LBD (Est 0.08, SE 0.03, valor p 0.008) después de ajustar por edad, sexo, comorbilidad, síntomas neuropsiquiátricos y cognición. Para cada medicamento agregado durante el seguimiento, funcional las trayectorias empeoraron en un 1% para AD y 2% para LBD. El número de medicamentos no se asoció con factores cognitivos. disminución. Conclusión: Encontramos que un mayor número de medicamentos se relacionó con un deterioro funcional más rápido, tanto en la EA y LBD. La prescripción, especialmente en la demencia, debe evaluarse cuidadosamente, por lo que el pronóstico en la demencia podría posiblemente se mejore.Q1Q1Background: In dementia, a number of factors may influence functional decline in addition to cognition. In this study, we aim to study the potential association of the number of prescribed medications with functional decline trajectories over a five-year follow-up in people diagnosed with mild Alzheimer's disease (AD) or Lewy Body dementia(LBD). Methods: This is a longitudinal analysis of a Norwegian cohort study entitled “The Dementia Study of Western Norway”. We included 196 patients newly diagnosed with AD (n=111) and LBD (n=85), followed annually for 5 years. We conducted linear mixed-effects models to analyze the association of the number of medications with functional decline measured by the Rapid Disability Rating Scale – 2. Results: The mean prescribed medications at baseline was 4.18∓2.60, for AD 3.92∓2.51 and LBD 4.52∓2.70. The number of medications increased during the follow-up; at year five the mean for AD was 7.28∓4.42 and for LBD 8.11∓5.16. Using more medications was associated with faster functional decline in AD (Est 0.04,SE0.01, p-value 0.003) and LBD (Est 0.08, SE 0.03, p-value 0.008) after adjusting for age, sex, comorbidity, neuropsychiatric symptoms, and cognition. For each medication added during the follow-up, functional trajectories worsened by 1% for AD and 2% for LBD. The number of medications was not associated with cognitive decline. Conclusion: We found that higher number of medications was related to a faster functional decline, both in AD and LBD. Prescription especially in dementia should be carefully assessed, thus prognosis in dementia might possibly be improved.https://orcid.org/0000-0001-5832-0603https://scholar.google.com/citations?user=MrICwaMAAAAJ&hl=enhttps://scienti.minciencias.gov.co/cvlac/visualizador/generarCurriculoCv.do?cod_rh=0001429659&lang=esRevista Internacional - Indexad

Benzodiazepines and antidepressants: Effects on cognitive and functional decline in Alzheimer's disease and Lewy body dementia

Objectives We aim to study the effects of the prescription of benzodiazepines and antidepressants on cognitive and functional decline in older adults living with Alzheimer's disease (AD) and Lewy body dementia (LBD) over a 5-year follow-up. Methods This is a longitudinal analysis of a Norwegian cohort study entitled “The Dementia Study of Western Norway” (DemVest). We included 196 patients newly diagnosed with AD (n = 111) and LBD (n = 85), followed annually for 5 years. Three prescription groups were defined: only benzodiazepines (BZD), only antidepressants (ADep), and the combination of benzodiazepines and antidepressants (BZD-ADep). Linear mixed-effects models were conducted to analyze the effect of the defined groups on the outcomes. The outcomes were functional decline, measured by the Rapid Disability Rating Scale—2, and cognition measured with the Mini-Mental State Examination. Results Prescription of the combination of benzodiazepines and antidepressants in LBD was associated with faster functional decline. In AD, the prescription of BZD and BZD-ADep was associated with greater functional deterioration. ADep alone did not show positive or negative significant associations with the studied outcomes. Conclusions BZD and especially the combination of BZD and ADep are associated with functional decline in AD and LBD and should be used cautiously.publishedVersio

Effects of purified anthocyanins in people at risk for dementia: Study protocol for a phase II randomized controlled trial

Background: The number of people with dementia is increasing, with huge challenges for society and health-care systems. There are no disease-modifying therapies available. There is, therefore, an urgent need to identify strategies to reduce the risk of developing dementia. Anthocyanins are a class of compounds found in dark berries and fruits with some effects that might reduce the risk for cognitive decline and the development of dementia in older people. Aim: This phase II three-center, randomized, 24-week, placebo-controlled study, ongoing in Norway, aims to evaluate the safety, and efficacy of anthocyanins in modifying key dementia-related mechanisms and maintain cognitive functioning in older people at risk for dementia. Methods: Participants (220 individuals aged 60–80 years) who meet the inclusion criteria (either mild cognitive impairment or two or more cardiometabolic disorders) are being enrolled in this study at three different centers in Norway. Participants are block randomized to identically appearing capsules containing 80 mg of naturally purified anthocyanins or placebo 1:1. Dosage is 2 + 2 capsules per day for 24 weeks. The primary outcome will be the quality of episodic memory score, a composite measure from the extensively validated online cognitive test battery CogTrack®, which is administered at baseline and monthly for the next 6 months. Secondary outcomes include other major scores from CogTrack, as well as a range of neuroimaging and other biomarkers. Anthocyanin metabolites will be measured in blood and cerebrospinal fluid. The change from baseline scores will be subject to a mixed model for repeated measures analysis of covariance. The primary comparison will be the contrast (difference in the least-square means) between active and placebo at the end of the study (week 24). The primary study population will be a modified intention-to-treat population (ClinicalTrials.gov, NCT03419039). Discussion: This study aims to demonstrate whether there are beneficial effects of purified anthocyanins on cognition and relevant biological functions in people at increased risk for dementia. Forthcoming results may contribute to further improvement of intervention strategies to prevent or delay the onset of dementia, including a potential decision to take anthocyanins toward phase III trials.publishedVersio

Benzodiazepines and antidepressants: Effects on cognitive and functional decline in Alzheimer's disease and Lewy body dementia

Objectives We aim to study the effects of the prescription of benzodiazepines and antidepressants on cognitive and functional decline in older adults living with Alzheimer's disease (AD) and Lewy body dementia (LBD) over a 5-year follow-up. Methods This is a longitudinal analysis of a Norwegian cohort study entitled “The Dementia Study of Western Norway” (DemVest). We included 196 patients newly diagnosed with AD (n = 111) and LBD (n = 85), followed annually for 5 years. Three prescription groups were defined: only benzodiazepines (BZD), only antidepressants (ADep), and the combination of benzodiazepines and antidepressants (BZD-ADep). Linear mixed-effects models were conducted to analyze the effect of the defined groups on the outcomes. The outcomes were functional decline, measured by the Rapid Disability Rating Scale—2, and cognition measured with the Mini-Mental State Examination. Results Prescription of the combination of benzodiazepines and antidepressants in LBD was associated with faster functional decline. In AD, the prescription of BZD and BZD-ADep was associated with greater functional deterioration. ADep alone did not show positive or negative significant associations with the studied outcomes. Conclusions BZD and especially the combination of BZD and ADep are associated with functional decline in AD and LBD and should be used cautiously.publishedVersio

A Randomised Placebo-Controlled Study of Purified Anthocyanins on Cognition in Individuals at Increased Risk for Dementia

Importance Identifying nutritional compounds which can reduce cognitive decline in older people is a hugely important topic. Objective To study the safety and effect of anthocyanins in maintaining cognitive functioning in people at increased risk for dementia. Design, setting, and participants Participants (206 individuals, aged 60–80 years) diagnosed with either mild cognitive impairment (MCI) or two or more cardiometabolic disorders (i.e., diabetes, hypertension, obesity) were enrolled at three different centres in Norway. Intervention Participants were randomly assigned to four capsules with a total of 320 mg/d of naturally purified anthocyanins or placebo 1:1 for 24 weeks. Main outcomes and measures The primary outcome was the Quality of Episodic Memory composite measure (0–100) from an online cognitive test battery CogTrack, which was administered at baseline and monthly for the next 24 weeks. Secondary outcomes included other cognitive scores from the CogTrack battery. We applied mixed effects models with a baseline test score, group, time and their interaction as fixed effects, as well as other predefined baseline covariates. The primary comparison was the group difference at week 24 based on a modified intention-to-treat principle. Results : The primary analysis did not show a significant group difference at 24 weeks (78.2 versus 76.8; adjusted mean difference 1.4 (95% confidence interval -0.9–3.7); effect size 0.15; p = 0.23). However, there was a significant difference in slopes during weeks 8–24 (p = 0.007); the anthocyanin group improved while the placebo group worsened. No differences were found for the secondary cognitive outcomes. Anthocyanin capsules were well-tolerated and safe to use. Conclusion Anthocyanin supplementation for 24 weeks was safe and well tolerated in people with MCI or cardiometabolic disorders. We found no significant group difference in episodic memory at the end of the study but statistically significant differences in slopes. Further studies are warranted to explore whether anthocyanins supplementation can reduce cognitive decline in people at increased risk of dementia.publishedVersio

Long-Term Mortality in a Cohort of Home-Dwelling Elderly with Mild Alzheimer's Disease and Lewy Body Dementia

&lt;b&gt;&lt;i&gt;Objective:&lt;/i&gt;&lt;/b&gt; To study mortality in subjects with mild dementia in Norway with a special focus on patients with Lewy body dementia (LBD) compared to Alzheimer's disease (AD). &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; All referrals of mild dementia patients to dementia clinics in western Norway from March 2005 to March 2007 were included and followed until December 2012. Diagnoses were based on a comprehensive standardized assessment program. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Of 209 patients, 137 (66%) had AD and 53 (25%) had LBD. Dementia was associated with increased mortality (standardized mortality ratio = 1.8, AD 1.5, LBD 2.6). The median survival time was 6.2 years (95% CI 5.4-6.9). Predictors of mortality were age at diagnosis (HR 1.1 per year) and LBD diagnosis (HR 2.4). &lt;b&gt;&lt;i&gt;Conclusion:&lt;/i&gt;&lt;/b&gt; Dementia patients had an increased mortality, particularly those with LBD.</jats:p

A Randomised Placebo-Controlled Study of Purified Anthocyanins on Cognition in Individuals at Increased Risk for Dementia

Importance Identifying nutritional compounds which can reduce cognitive decline in older people is a hugely important topic. Objective To study the safety and effect of anthocyanins in maintaining cognitive functioning in people at increased risk for dementia. Design, setting, and participants Participants (206 individuals, aged 60–80 years) diagnosed with either mild cognitive impairment (MCI) or two or more cardiometabolic disorders (i.e., diabetes, hypertension, obesity) were enrolled at three different centres in Norway. Intervention Participants were randomly assigned to four capsules with a total of 320 mg/d of naturally purified anthocyanins or placebo 1:1 for 24 weeks. Main outcomes and measures The primary outcome was the Quality of Episodic Memory composite measure (0–100) from an online cognitive test battery CogTrack, which was administered at baseline and monthly for the next 24 weeks. Secondary outcomes included other cognitive scores from the CogTrack battery. We applied mixed effects models with a baseline test score, group, time and their interaction as fixed effects, as well as other predefined baseline covariates. The primary comparison was the group difference at week 24 based on a modified intention-to-treat principle. Results : The primary analysis did not show a significant group difference at 24 weeks (78.2 versus 76.8; adjusted mean difference 1.4 (95% confidence interval -0.9–3.7); effect size 0.15; p = 0.23). However, there was a significant difference in slopes during weeks 8–24 (p = 0.007); the anthocyanin group improved while the placebo group worsened. No differences were found for the secondary cognitive outcomes. Anthocyanin capsules were well-tolerated and safe to use. Conclusion Anthocyanin supplementation for 24 weeks was safe and well tolerated in people with MCI or cardiometabolic disorders. We found no significant group difference in episodic memory at the end of the study but statistically significant differences in slopes. Further studies are warranted to explore whether anthocyanins supplementation can reduce cognitive decline in people at increased risk of dementia. Trial registration ClinicalTrials.gov, (Identifier NCT03419039). http://www.clinicaltrials.gov/, NCT03419039