Maria Eriksdotter

Mild cognitive impairment and deficits in instrumental activities of daily living: a systematic review

IntroductionThere is a growing body of evidence that subtle deficits in instrumental activities of daily living (IADL) may be present in mild cognitive impairment (MCI). However, it is not clear if there are IADL domains that are consistently affected across patients with MCI. In this systematic review, therefore, we aimed to summarize research results regarding the performance of MCI patients in specific IADL (sub)domains compared with persons who are cognitively normal and/or patients with dementia.MethodsThe databases PsycINFO, PubMed and Web of Science were searched for relevant literature in December 2013. Publications from 1999 onward were considered for inclusion. Altogether, 497 articles were retrieved. Reference lists of selected articles were searched for potentially relevant articles. After screening the abstracts of these 497 articles, 37 articles were included in this review.ResultsIn 35 studies, IADL deficits (such as problems with medication intake, telephone use, keeping appointments, finding things at home and using everyday technology) were documented in patients with MCI. Financial capacity in patients with MCI was affected in the majority of studies. Effect sizes for group differences between patients with MCI and healthy controls were predominantly moderate to large. Performance-based instruments showed slight advantages (in terms of effect sizes) in detecting group differences in IADL functioning between patients with MCI, patients with Alzheimer’s disease and healthy controls.ConclusionIADL requiring higher neuropsychological functioning seem to be most severely affected in patients with MCI. A reliable identification of such deficits is necessary, as patients with MCI with IADL deficits seem to have a higher risk of converting to dementia than patients with MCI without IADL deficits. The use of assessment tools specifically designed and validated for patients with MCI is therefore strongly recommended. Furthermore, the development of performance-based assessment instruments should be intensified, as they allow a valid and reliable assessment of subtle IADL deficits in MCI, even if a proxy is not available. Another important point to consider when designing new scales is the inclusion of technology-associated IADL. Novel instruments for clinical practice should be time-efficient and easy to administer.

Omega-3 fatty acids enhance phagocytosis of Alzheimer's disease-related amyloid-β42 by human microglia and decrease inflammatory markers.

The use of supplements with omega-3 (ω3) fatty acids (FAs) such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) is widespread due to proposed beneficial effects on the nervous and cardiovascular systems. Many effects of ω3 FAs are believed to be caused by down-regulation and resolution of inflammation. Alzheimers disease (AD) is associated with inflammation mediated by microglia and astrocytes, and ω3 FAs have been proposed as potential treatments for AD. The focus of the present study is on the effects of DHA and EPA on microglial phagocytosis of the AD pathogen amyloid-β (Aβ), on secreted and cellular markers of immune activity, and on production of brain-derived neurotrophic factor (BDNF). Human CHME3 microglial cells were exposed to DHA or EPA, with or without the presence of Aβ42. Phagocytosis of Aβ42 was analyzed by flow cytometry in conjunction with immunocytochemistry using antibodies to cellular proteins. Secreted proteins were analyzed by ELISA. Both DHA and EPA were found to stimulate microglial phagocytosis of Aβ42. Phagocytosis of Aβ42 was performed by microglia with a predominance of M2 markers. EPA increased the levels of BDNF in the culture medium. The levels of TNF-α were decreased by DHA. Both DHA and EPA decreased the pro-inflammatory M1 markers CD40 and CD86, and DHA had a stimulatory effect on the anti-inflammatory M2 marker CD206. DHA and EPA can be beneficial in AD by enhancing removal of Aβ42, increasing neurotrophin production, decreasing pro-inflammatory cytokine production, and by inducing a shift in phenotype away from pro-inflammatory M1 activation.

Resolution of inflammation is altered in Alzheimer's disease.

Resolution is the final stage of the inflammatory response, when restoration of tissue occurs. Failure may lead to chronic inflammation, which is known as part of the pathology in the brain of individuals with Alzheimers disease (AD).

CSF neurofilament light differs in neurodegenerative diseases and predicts severity and survival.

Objectives: We hypothesized that CSF neurofilament light (NFL) levels would be elevated in dementias with subcortical involvement, including vascular dementia (VaD), but less elevated in dementias primarily affecting gray matter structures, such as Alzheimer disease (AD), and that elevated CSF NFL would correlate with disease severity and shorter survival time irrespective of clinical diagnosis. Methods: We included 3,356 individuals with dementia who had CSF NFL analyzed in our laboratory between 2005 and 2012. Clinical diagnoses and Mini-Mental State Examination (MMSE) scores were obtained from the Swedish Dementia Registry, and in selected cases (n = 478), date of death from the Swedish Mortality Registry. Results: CSF NFL differed among clinical diagnoses, with the highest levels seen in frontotemporal dementia, VaD, and mixed AD and VaD. Early-onset AD (younger than 65 years) had the lowest levels. High CSF NFL correlated with low MMSE score and short survival time irrespective of diagnosis, and was also particularly evident in AD. Conclusions: CSF NFL differs among different neurodegenerative diseases and is especially high in dementias engaging subcortical brain regions, such as VaD and mixed AD and VaD, but also in frontotemporal dementia. The association of high CSF NFL levels with disease severity and short survival supports the notion that high CSF NFL levels indicate more aggressive disease processes.

The use of cholinesterase inhibitors and the risk of myocardial infarction and death: a nationwide cohort study in subjects with Alzheimer's disease

AIMS Cholinesterase inhibitors (ChEIs) are used for symptomatic treatment of Alzheimers disease. These drugs have vagotonic and anti-inflammatory properties that could be of interest also with respect to cardiovascular disease. This study evaluated the use of ChEIs and the later risk of myocardial infarction and death. METHODS AND RESULTS The cohort consisted of 7073 subjects (mean age 79 years) from the Swedish Dementia Registry with the diagnoses of Alzheimers dementia or Alzheimers mixed dementia since 2007. Cholinesterase inhibitor use was linked to diagnosed myocardial infarctions (MIs) and death using national registers. During a mean follow-up period of 503 (range 0-2009) days, 831 subjects in the cohort suffered MI or died. After adjustment for confounders, subjects who used ChEIs had a 34% lower risk for this composite endpoint during the follow-up than those who did not [hazard ratio (HR) 0.66, 95% confidence interval (CI) 0.56-0.78]. Cholinesterase inhibitor use was also associated with a lower risk of death (HR: 0.64, 95% CI: 0.54-0.76) and MI (HR: 0.62, 95% CI: 0.40-0.95) when analysed separately. Subjects taking the highest recommended ChEI doses (donepezil 10 mg, rivastigmine >6 mg, galantamine 24 mg) had the lowest risk of MI (HR: 0.35, 95% CI: 0.19-0.64), or death (HR: 0.54, 95% CI: 0.43-0.67) compared with those who had never used ChEIs. CONCLUSION Cholinesterase inhibitor use was associated with a reduced risk of MI and death in a nationwide cohort of subjects diagnosed with Alzheimers dementia. These associations were stronger with increasing ChEI dose.

Transfer of omega‐3 fatty acids across the blood–brain barrier after dietary supplementation with a docosahexaenoic acid‐rich omega‐3 fatty acid preparation in patients with Alzheimer's disease: the OmegAD study

Little is known about the transfer of essential fatty acids (FAs) across the human blood–brain barrier (BBB) in adulthood. In this study, we investigated whether oral supplementation with omega‐3 (n‐3) FAs would change the FA profile of the cerebrospinal fluid (CSF).

Mortality Risk after Dementia Diagnosis by Dementia Type and Underlying Factors: A Cohort of 15,209 Patients based on the Swedish Dementia Registry

BACKGROUND Knowledge on survival in dementia is crucial for patients and public health planning. Most studies comparing mortality risk included few different dementia diagnoses. OBJECTIVES To compare mortality risk in the most frequent dementia disorders in a large cohort of patients with an incident diagnosis, adjusting for potential confounding factors. METHODS 15,209 patients with dementia from the national quality database, Swedish Dementia Registry (SveDem), diagnosed in memory clinics from 2008 to 2011, were included in this study. The impact of age, gender, dementia diagnosis, baseline Mini-Mental State Examination (MMSE), institutionalization, coresidency, and medication on survival after diagnosis were examined using adjusted hazard ratios (HR) with 95% confidence intervals (CI). RESULTS During a mean follow-up of 2.5 years, 4,287 deaths occurred, with 114 (95% CI 111-117) deaths/1,000 person-years. Adjusted HR of death for men was 1.56 (95% CI 1.46-1.66) compared to women. Low MMSE, institutionalization, and higher number of medications were associated with higher HR of death. All dementia diagnoses demonstrated higher HR compared to Alzheimers disease, with vascular dementia presenting the highest crude HR. After adjusting, frontotemporal dementia had the highest risk with a HR of 1.91 (95% CI 1.52-2.39), followed by Lewy body dementia (HR 1.64; 95% CI 1.39-1.95), vascular dementia (HR 1.55; 95% CI 1.42-1.69), Parkinsons disease dementia (HR 1.47; 95% CI 1.17-1.84), and mixed Alzheimers disease and vascular dementia (HR 1.32; 95% CI 1.22-1.44). CONCLUSION Worse cognition, male gender, higher number of medications, institutionalization, and age were associated with increased death risk after dementia diagnosis. Adjusted risk was lowest in Alzheimers disease patients and highest in frontotemporal dementia subjects.

Heart failure and Alzheimer′s disease

It has recently been proposed that heart failure is a risk factor for Alzheimer′s disease. Decreased cerebral blood flow and neurohormonal activation due to heart failure may contribute to the dysfunction of the neurovascular unit and cause an energy crisis in neurons. This leads to the impaired clearance of amyloid beta and hyperphosphorylation of tau protein, resulting in the formation of amyloid beta plaques and neurofibrillary tangles. In this article, we will summarize the current understanding of the relationship between heart failure and Alzheimer′s disease based on epidemiological studies, brain imaging research, pathological findings and the use of animal models. The importance of atherosclerosis, myocardial infarction, atrial fibrillation, blood pressure and valve disease as well as the effect of relevant medications will be discussed.

SveDem, the Swedish Dementia Registry - A Tool for Improving the Quality of Diagnostics, Treatment and Care of Dementia Patients in Clinical Practice

Background The Swedish Dementia Registry (SveDem) was developed with the aim to improve the quality of diagnostic work-up, treatment and care of patients with dementia disorders in Sweden. Methods SveDem is an internet based quality registry where several indicators can be followed over time. It includes information about the diagnostic work-up, medical treatment and community support (www.svedem.se). The patients are diagnosed and followed-up yearly in specialist units, primary care centres or in nursing homes. Results The database was initiated in May 2007 and covers almost all of Sweden. There were 28 722 patients registered with a mean age of 79.3 years during 2007–2012. Each participating unit obtains continuous online statistics from its own registrations and they can be compared with regional and national data. A report from SveDem is published yearly to inform medical and care professionals as well as political and administrative decision-makers about the current quality of diagnostics, treatment and care of patients with dementia disorders in Sweden. Conclusion SveDem provides knowledge about current dementia care in Sweden and serves as a framework for ensuring the quality of diagnostics, treatment and care across the country. It also reflects changes in quality dementia care over time. Data from SveDem can be used to further develop the national guidelines for dementia and to generate new research hypotheses.

Effects of n-3 FA supplementation on the release of proresolving lipid mediators by blood mononuclear cells : the OmegAD study

Specialized proresolving mediators (SPMs) induce resolution of inflammation. SPMs are derivatives of n-3 and n-6 PUFAs and may mediate their beneficial effects. It is unknown whether supplementation with PUFAs influences the production of SPMs. Alzheimer’s disease (AD) is associated with brain inflammation and reduced levels of SPMs. The OmegAD study is a randomized, double-blind, and placebo-controlled clinical trial on AD patients, in which placebo or a supplement of 1.7 g DHA and 0.6 g EPA was taken daily for 6 months. Plasma levels of arachidonic acid decreased, and DHA and EPA levels increased after 6 months of n-3 FA treatment. Peripheral blood mononuclear cells (PBMCs) were obtained before and after the trial. Analysis of the culture medium of PBMCs incubated with amyloid-β 1–40 showed unchanged levels of the SPMs lipoxin A4 and resolvin D1 in the group supplemented with n-3 FAs, whereas a decrease was seen in the placebo group. The changes in SPMs showed correspondence to cognitive changes. Changes in the levels of SPMs were positively correlated to changes in transthyretin. We conclude that supplementation with n-3 PUFAs for 6 months prevented a reduction in SPMs released from PBMCs of AD patients, which was associated with changes in cognitive function.