Alzheimer Disease: Solomon A

Kivipelto M, Solomon A. · No affiliation provided · BMJ. · Pubmed #16690644 links to  free full text

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Winblad B, Fioravanti M, Dolezal T, Logina I, Milanov IG, Popescu DC, Solomon A. · Karolinska Institute - Alzheimer Disease Research Center, Stockholm, Sweden. · Clin Drug Investig. · Pubmed #18666801 No free full text.

Abstract: The ergot alkaloid derivative nicergoline became clinically available about 35 years ago in the 1970s. Nicergoline has a broad spectrum of action: (i) as an alpha(1)-adrenoceptor antagonist, it induces vasodilation and increases arterial blood flow; (ii) it enhances cholinergic and catecholaminergic neurotransmitter function; (iii) it inhibits platelet aggregation; (iv) it promotes metabolic activity, resulting in increased utilization of oxygen and glucose; and (v) it has neurotrophic and antioxidant properties. Acting on several basic pathophysiological mechanisms, nicergoline has therapeutic potential in a number of disorders. This article provides an overview of the published clinical evidence relating to the efficacy and safety of nicergoline (30 mg twice daily) in the treatment of dementia (including Alzheimer's disease and vascular dementia) and vascular and balance disorders. For dementia of different aetiologies, the therapeutic benefit of nicergoline has been established, with up to 89% of patients showing improvements in cognition and behaviour. After as little as 2 months of treatment, symptom improvement is apparent compared with placebo, and most patients are still improved or stable after 12 months. Concomitant neurophysiological changes in the brain indicate (after only 4-8 weeks' treatment) improved vigilance and information processing. In patients with balance disorders, mean improvements of 44-78% in symptom severity and quality of life have been observed with nicergoline. Although clinical experience with nicergoline in vascular disorders is limited to relatively short-term, small-scale studies, it has been successfully used in rehabilitation therapy of patients with chronic ischaemic stroke. Open-label evaluations suggest that nicergoline may also be valuable in glaucoma, depression and peripheral arterio-pathy. Adverse events of nicergoline, if any, are related to the central nervous system, the metabolic system and the overall body. Most are considered typical symptoms of ergot derivatives. Because of their generally mild and transient nature, treatment discontinuations occur relatively infrequently. The efficacy of nicergoline combined with a favourable safety and tolerability profile at commonly applied doses (60 mg/day) make this agent a valuable therapy in patients with mild to moderate dementia, vascular diseases and balance disorders.

Kivipelto M, Solomon A. · Aging Research Center, Karolinska Institutet, Gavlegatan 16, S-113 30 Stockholm, Sweden. · J Nutr Health Aging. · Pubmed #18165854 No free full text.

Abstract: Several vascular and lifestyle related factors have been suggested to influence the development of dementia and Alzheimer's disease (AD), creating new prevention opportunities. This paper discusses current epidemiological evidence and new findings from the Finnish population based CAIDE study linking some of these factors to dementia/AD. Such findings provide an optimistic outlook especially for persons with genetic susceptibility; it may be possible to reduce the risk or postpone the onset of dementia by adopting healthy lifestyle options. The interplay of genes and environment in the aetiology of AD needs to be further investigated as well as the role of lifestyle and pharmacological interventions for the prevention of dementia.

Kivipelto M, Solomon A. · Department of Clinical Geriatrics, Karolinska Institutet, Stockholm, Sweden. · Acta Neurol Scand Suppl. · Pubmed #16866911 No free full text.

Abstract: Although dementia is usually a late-life syndrome, it is now well known that pathological changes begin quite early in adulthood, outside the classical age borders of geriatric specialties. In order to design effective preventive strategies, adequate information can only be gathered by taking a life-long view of Alzheimer's disease (AD). Dementia risk is the result of exposure to both harmful and protective factors along the life course, and these factors, as well as their impact on the individual's health status, change over time. This review aims at presenting current epidemiological data on serum cholesterol levels and dietary fat intake as risk factors for dementia/AD, and at discussing the reasons and significance of contradictions between various studies. Reducing dementia risk may be possible by influencing the serum lipid profile. A more detailed characterization of the mechanisms behind the association of cholesterol (in both serum and brain) with dementia/AD, mechanisms about which little is currently known, would allow a better translation of research findings into clinical practice.

Solomon A, Kivipelto M. · Aging Research Center, Karolinska Institutet, Sweden. · Expert Rev Neurother. · Pubmed #19402779 No free full text.

Abstract: The link between cholesterol and Alzheimer's disease (AD) is indicated by genetic, epidemiological, experimental and clinical evidence, although the relationship is far from simple or straightforward. Compared with extracerebral cholesterol, little is known about brain cholesterol homeostasis. In addition, current diagnostic criteria for AD exclude a priori the pathogenic participation of vascular factors (to which cholesterol is traditionally associated), and require modifications. Randomized controlled trials suggest that the dementia stage of AD may already be too late for significant benefits of statin therapy, emphasizing the importance of early diagnosis and treatment. Cholesterol-modifying strategies may be more effective in dementia/AD prevention. Since cholesterol is only one piece of the dementia/AD puzzle, integrative interventions (lifestyle-related and, when necessary, pharmacologic) focusing on overall risk instead of individual risk factors may bring more benefit to individuals at risk.

Shafaati M, Solomon A, Kivipelto M, Björkhem I, Leoni V. · Department of Laboratory Medicine, Division of Clinical Chemistry, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden. · Neurosci Lett. · Pubmed #17822846 No free full text.

Abstract: Evidence was recently presented from in vitro studies that 24S-hydroxycholesterol acts as a signalling molecule inducing apoE-mediated cholesterol efflux from astrocytoma cells, and that there is a direct effect of the oxysterol on apoE transcription, protein synthesis and secretion. Consistent with this mechanism, a significant correlation is demonstrated here between levels of apoE and 24S-hydroxycholesterol in cerebrospinal fluid from patients with Alzheimer's disease and patients with mild cognitive impairment. Such a correlation was not found in control patients. There was no correlation between levels of apoE and cholesterol in cerebrospinal fluid from controls. The results are consistent with a close coupling between release of 24S-hydroxycholesterol and apoE secretion under conditions with neuronal degeneration. The levels of apoE in cerebrospinal fluid were also correlated to the levels of Tau and the possibility is discussed that the level of apoE in cerebrospinal fluid may be used as a marker of neurodegeneration.

Solomon A, Kåreholt I, Ngandu T, Winblad B, Nissinen A, Tuomilehto J, Soininen H, Kivipelto M. · Department of Neuroscience and Neurology, University of Kuopio, Finland. · Neurology. · Pubmed #17339582 No free full text.

Abstract: BACKGROUND: Longitudinal studies have shown that high serum total cholesterol (TC) at midlife is a risk factor for dementia/Alzheimer disease. The significance of TC later in life is unclear. OBJECTIVE: To investigate changes in serum TC from midlife to late life and their relationship with late-life cognition. METHODS: Participants of the Cardiovascular Risk Factors, Aging and Dementia study were derived from random, population-based samples previously studied in a survey in 1972, 1977, 1982, or 1987. After an average follow-up of 21 years, 1,449 individuals aged 65 to 79 were reexamined in 1998. RESULTS: Serum TC levels decreased in most individuals. High midlife TC represented a risk factor for more severe cognitive impairment later in life, and the values were significantly different between the control, mild cognitive impairment, and dementia groups. There were no significant differences in serum TC at reexamination. A moderate decrease in serum TC from midlife to late life (0.5 to 2 mmol/L) was significantly associated with the risk of a more impaired late-life cognitive status, even after adjusting for age, follow-up time, sex, years of formal education, midlife cholesterol, changes in body mass index, APOE epsilon4 genotype, history of myocardial infarction/stroke/diabetes, and lipid-lowering treatment. CONCLUSIONS: The relationship between serum total cholesterol (TC) and dementia seems to be bidirectional. High midlife serum TC is a risk factor for subsequent dementia/Alzheimer disease, but decreasing serum TC after midlife may reflect ongoing disease processes and may represent a risk marker for late-life cognitive impairment.

Kivipelto M, Solomon A, Winblad B. · Department of Clinical Geriatrics, Karolinska Institutet, Stockholm, Sweden. · Acta Neurol Scand Suppl. · Pubmed #16866921 No free full text.

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Kivipelto M, Solomon A, Blennow K, Olsson AG, Winblad B. · Department of Clinical Geriatrics, Karolinska Institutet, Stockholm, Sweden. · Acta Neurol Scand Suppl. · Pubmed #16866903 No free full text.

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Kaplan B, Hrncic R, Murphy CL, Gallo G, Weiss DT, Solomon A. · Heller Institute of Medical Research, Chaim Sheba Medical Center, Tel Hashomer, Israel. · Methods Enzymol. · Pubmed #10507017 No free full text.

Abstract: This article described micromethods useful for the extraction, purification, and amino acid sequencing of amyloid proteins contained in minute specimens obtained from patients with systemic forms of amyloidosis. We posit that these procedures can also be applied to the biochemical characterization of cerebral amyloid deposits. The selection of the techniques is dependent on the type of sample to be extracted (fresh or formalin fixed) as well as the amount of congophilic material present. Although amyloid proteins are isolated and purified more easily from fresh tissue, it must be noted that formalin-fixed specimens are available more readily for analysis due to the common diagnostic use of fine needle tissue biopsies and are therefore, important for both current and retrospective studies. Remarkably, despite the expected difficulties associated with formalin treatment we were able to extract and sequence amyloid proteins from fixed tissues presumably due to the resistance of amyloid to formalin cross-linking. Through the continued development of techniques for small-scale protein separation and application of highly sensitive microsequencing and mass spectral methods, exact identification of the protein contained in fibrillar amyloid deposits can be determined. Such information has therapeutic and prognostic relevance and can increase our understanding of the pathogenesis of amyloidosis.

Kivipelto M, Solomon A, Winblad B. · No affiliation provided · Lancet Neurol. · Pubmed #16109358 No free full text.

This publication has no abstract.