Your search for: 'author:("Soininen, Hilkka")' has returned 81 results. (0.012s) Save search

Authors: Solomon, Alina | Kivipelto, Miia | Soininen, Hilkka

Article Type: Review Article

Abstract: This is a brief summary of experiences from Finland related to Alzheimer's disease (AD) prevention research. The first signals that AD may have vascular modifiable risk factors came from studies on cardiovascular conditions and diabetes. Cardiovascular prevention projects such as North Karelia Project and WHO-MONICA in the 1970–1980 s were focused on younger populations, which led to the idea of looking for risk factors as far back as middle age. Cardiovascular Risk Factors, Aging and Incidence of Dementia (CAIDE) is one of the few studies in the world focusing on late-life cognition with a large and representative population-based cohort, baseline …examination at midlife, and follow-up time up to three decades. Since 1998, it has identified several modifiable risk factors for cognitive impairment/dementia, and produced the first risk score for estimating dementia risk based on midlife profiles. The CAIDE Dementia Risk Score has been used to select participants in the Finnish Geriatric Intervention Study to prevent cognitive impairment and disability (FINGER). FINGER is an ongoing multicenter RCT involving 1,200 participants aged 60–77 years, and testing the effects of a two-year multi-domain intervention targeting several risk factors simultaneously. It started in September 2009 and will be completed at the end of 2013. The FINGER study is at the forefront of international collaborative efforts to solve the clinical and public health problems of early identification of individuals at increased risk of late-life cognitive impairment, and of developing intervention strategies to prevent or delay the onset of cognitive impairment and dementia. Show more

Keywords: Alzheimer's disease cognitive impairment, epidemiology, prevention, randomized controlled trials

DOI: 10.3233/JAD-2012-129021

Citation: Journal of Alzheimer's Disease, vol. 33, no. s1, pp. S465-S469, 2013

Authors: Iqbal, Khalid | Flory, Michael | Soininen, Hilkka

Article Type: Research Article

Abstract: Alzheimer's disease (AD) is a multifactorial disorder that involves several different mechanisms. Over 99% of AD patients suffer from the sporadic form of the disease. Based on cerebrospinal fluid (CSF) levels of amyloid-β (Aβ)1-42 , total tau, and ubiquitin—the markers associated with the histopathological hallmarks of the disease (Aβ plaques and abnormally hyperphosphorylated neurofibrillary tangles)—previous studies identified five subgroups of AD. Here we report the potential diagnostic predictive value of hallucination, hypokinesia, paranoia, rigidity, and tremors in aged individuals for AD and differences in the prevalence of these symptoms in the CSF marker-based subgroups of the disease. Analysis of 196 …clinically diagnosed AD or Alzheimer with Lewy body, and 75 non-AD neurological and non-neurological control cases, all from a single center, showed that the presence of hallucination, hypokinesia, paranoia, rigidity, or tremors individually, or the presence of any of these, could diagnose AD with sensitivities and specificities of 14% and 99%; 30% and 99%; 15% and 99%; 16% and 100%; 16% and 96%; and 47% and 92%, respectively. The pattern of the prevalence of the above symptoms varied from AD subgroup to subgroup. Presence of any of these symptoms, as well as presence of each individual symptom except tremors, significantly differentiated AD subgroups from the predominantly control cluster. These findings encourage the exploration of hallucination, hypokinesia, paranoia, rigidity, and tremors in identifying various subgroups of AD for stratification of patients for clinical trials to develop therapeutic drugs. This study is for the special issue of the Journal of Alzheimer's Disease honoring Inge Grundke-Iqbal who made several seminal contributions in AD research. Show more

Keywords: Alzheimer's disease subgroups, hallucination, hypokinesia, paranoia, rigidity, tremors

DOI: 10.3233/JAD-130899

Citation: Journal of Alzheimer's Disease, vol. 37, no. 3, pp. 475-481, 2013

Authors: Tolppanen, Anna-Maija | Solomon, Alina | Soininen, Hilkka | Kivipelto, Miia

Article Type: Review Article

Abstract: The shared risk factor profile between cardiovascular diseases and Alzheimer's disease (AD), observations on vascular pathology in AD, and altered cerebral blood flow in AD brains have led to the suggestion that AD might be a vascular disorder with neurodegenerative consequences. Targeting vascular and metabolic risk factors could be an effective way to prevent AD. Higher body mass index, elevated blood pressure, serum cholesterol concentrations, and impaired glucose regulation have been associated with increased risk of AD. Interestingly, the associations between these factors measured at mid-life are stronger, or even opposite, than with the risk factors measured at late-life. This …may reflect true differences in the association (i.e., mid-life risk factors being a better measure of vascular load during adulthood), reverse causality, or bias. The vascular risk factors can directly increase the susceptibility to AD, or the effect can be mediated via cardio- and cerebrovascular diseases. Show more

Keywords: Alzheimer's disease, blood pressure, cholesterol, diabetes mellitus, epidemiology, metabolic syndrome X, obesity, risk factors, stroke, vascular diseases

DOI: 10.3233/JAD-2012-120802

Citation: Journal of Alzheimer's Disease, vol. 32, no. 3, pp. 531-540, 2012

Authors: Kaarniranta, Kai | Salminen, Antero | Haapasalo, Annakaisa | Soininen, Hilkka | Hiltunen, Mikko

Article Type: Review Article

Abstract: Age-related macular degeneration (AMD) is a late-onset, neurodegenerative retinal disease that shares several clinical and pathological features with Alzheimer's disease (AD), including stress stimuli such as oxidative stress and inflammation. In both diseases, the detrimental intra- and extracellular deposits have many similarities. Aging, hypercholesterolaemia, hypertension, obesity, arteriosclerosis, and smoking are risk factors to develop AMD and AD. Cellular aging processes have similar organelle and signaling association in the retina and brain tissues. However, it seems that these diseases have a different genetic background. In this review, differences and similarities of AMD and AD are thoroughly discussed.

Keywords: Age-related macular degeneration (AMD), aggregation, aging, Alzheimer's disease, autophagy, lysosome, oxidative stress, proteasome

DOI: 10.3233/JAD-2011-101908

Citation: Journal of Alzheimer's Disease, vol. 24, no. 4, pp. 615-631, 2011

Authors: Herukka, Sanna-Kaisa | Pennanen, Corina | Soininen, Hilkka | Pirttilä, Tuula

Article Type: Short Communication

Abstract: Cerebrospinal fluid (CSF) biomarkers and medial temporal lobe (MTL) atrophy predict the progression of mild cognitive impairment (MCI) to Alzheimer's disease (AD). We investigated the association between the CSF biomarkers and MTL atrophy and the ability of these measures to predict AD in MCI patients in the same study population. The study included 21 MCI patients of whom eight progressed to AD during the study. CSF biomarkers were measured by using ELISA method and volumes of MTL structures were assessed by magnetic resonance imaging (MRI). Aβ42 levels were lower and tau and phospho-tau levels were higher in progressive subjects. The …progressive subjects had lower volumes in all MRI measures. Tau and phospho-tau correlated inversely with hippocampal volumes and left entorhinal cortex volume in the whole study group. In the stable group, tau correlated with hippocampal volumes. Aβ42 had a negative correlation whereas phospho-tau exhibited a positive correlation with left hippocampal volume in the progressive group. These results indicate that both measures may reflect the ongoing neurodegenerative process in the progressive MCI patients. However, the order of the changes in the CSF biomarkers and MTL atrophy remain unclear due to a small number of studied subjects and study design. Show more

Keywords: Amyloid-β, cerebrospinal fluid, hippocampal atrophy, phosphorylated tau, tau

DOI: 10.3233/JAD-2008-14105

Citation: Journal of Alzheimer's Disease, vol. 14, no. 1, pp. 51-57, 2008

Authors: Yang, Hongqian | Lyutvinskiy, Yaroslav | Soininen, Hilkka | Zubarev, Roman A.

Article Type: Research Article

Abstract: Increased levels of isoaspartyl residues (isoAsp) have previously been found in proteins of Alzheimer's disease (AD) brains and in blood proteins of patients suffering from uremia, the disease sharing common pathological features with AD. One can hypothesize that higher levels of isoAsp should be present in blood proteins of AD patients. Also, because of higher AD prevalence in females, they can be expected to have higher level of isoAsp than males. Here we modified our recently developed proteome-wide isoAsp analysis approach for testing these hypotheses. Eight blood plasma samples pooled from 218 individuals suffering from either mild cognitive impairment (MCI) …or AD were analyzed by tandem mass spectrometry using electron transfer dissociation. Based on specific fragmentation pattern of isoAsp, the healthy controls were found to contain lower level of isoAsp compared with age-matched MCI and AD patients (p = 0.03). This result was further validated (p = 0.05) by 96 individual sample analyses, giving the combined value of p ≈ 0.01. Female pooled samples were found to contain higher level of isoAsp than male in both pooled and individual samples, with overall p ≈ 0.01. These findings verify the above hypotheses, and provide protein candidates for further investigation of the link between isoAsp and AD. Show more

Keywords: Aspartyl isomerization, blood plasma, electron capture dissociation, label-free quantification, tandem mass spectrometry

DOI: 10.3233/JAD-2011-110626

Citation: Journal of Alzheimer's Disease, vol. 27, no. 1, pp. 113-118, 2011

Authors: Alafuzoff, Irina | Overmyer, Margit | Helisalmi, Seppo | Soininen, Hilkka

Article Type: Research Article

Abstract: Epidemiological studies have indicated that non-steroidal anti-inflammatory drugs (NSAID) may have some therapeutic effect in Alzheimer's disease (AD) and experimental studies have shown that microglia activation by Aβ-peptide (Aβ) can be influenced by NSAIDs. We analysed 42 clinically and histopathologically verified demented patients fulfilling the histopathological CERAD criteria for definite AD, representing the terminal stage of brain degeneration. Our results indicate that regular NSAID use has a significant influence on the load of Aβ-peptide. Furthermore, our results indicate that regular NSAID use is associated with significantly lower counts of astrocytes and a trend of lower counts of activated microglia in …the brain tissue. The influence of NSAID use was noted in all ApoE genotypes however the trend of lower counts of glial cells with regular NSAID use was more marked in patients carrying the ApoE ε4/4 alleles. Based on our results one would anticipate that regular NSAID dosing could have a beneficial effect on the progression of the disease. However, the fact that we failed to observe significant differences for activated microglia might indicate an age or stage dependent difference in the glial response i.e. in their activation rate. More studies into age and stage related factors influencing the glial response are required if one is to devise novel pharmacological treatment strategies for AD. Show more

DOI: 10.3233/JAD-2000-2105

Citation: Journal of Alzheimer's Disease, vol. 2, no. 1, pp. 37-46, 2000

Authors: Imtiaz, Bushra | Tolppanen, Anna Maija | Solomon, Alina | Soininen, Hilkka | Kivipelto, Miia

Article Type: Short Communication

Abstract: Cardiovascular Risk factors, Aging and Dementia (CAIDE) is a Finnish population-based study. 731 cognitively normal women had self-reported hormone therapy (HT) data in 1998 as: no use, use ≤5 years, and >5 years. Information on type of HT was only available from 1995–1998 (Prescription Register). Cognition was assessed in 1998 and 2005–2008. Long-term (>5 years) HT use, especially use of estradiol alone among women having hysterectomy with bilateral oophorectomy, was associated with better episodic memory in 1998, but not in 2005–2008. Although a strong evidence for protective effect of estradiol on cognition was not observed in our study, improved global …cognition among long-term users suggests that long-term postmenopausal HT may be beneficial for some cognitive domains. Show more

Keywords: Cognition, dementia, estradiol, hormone therapy, menopause

DOI: 10.3233/JAD-160643

Citation: Journal of Alzheimer's Disease, vol. 56, no. 2, pp. 453-458, 2017

Authors: Wallin, Karin | Solomon, Alina | Kåreholt, Ingemar | Tuomilehto, Jaakko | Soininen, Hilkka | Kivipelto, Miia

Article Type: Research Article

Abstract: Inflammation has been associated with Alzheimer's disease (AD) and dementia. The association between rheumatoid arthritis (RA) or arthritis and dementia/AD has been investigated in several case-control or hospital- and register-based studies with mixed results. This long-term population-based study investigates the association between presence of joint disorders (RA and other joint disorders) in midlife and cognitive status later in life. 1,449 participants were first evaluated in 1972, 1977, 1982, and 1987 and follow-up was performed after 21 years. A self-administered questionnaire including questions on joint disorders was used at both evaluations. Cognitive status (control, mild cognitive impairment, dementia/AD) was assessed at …follow-up. The presence of any joint disorder in midlife was significantly associated with a worse cognitive status later in life: OR (95% CI) in an ordinal logistic regression analysis adjusted for age, gender, follow-up time, education, APOEε4, body mass index, smoking, drug treatment, and diabetes was 1.96 (1.17–3.28). For RA only, OR (95% CI) was 2.77 (1.26–6.10). The correlation remained significant for RA when AD was considered instead of dementia OR (95% CI) 2.49 (1.09–5.67). The presence of joint disorders, especially RA, at midlife seems to be associated with a worse cognitive status later in life. Given the chronic inflammatory component of RA, this study suggests that inflammatory mechanisms may have an important role in increasing the risk of cognitive impairment and dementia/AD. Show more

Keywords: Alzheimer's disease, cognitive impairment, dementia, epidemiology, inflammation, joint disorders, longitudinal, rheumatoid arthritis

DOI: 10.3233/JAD-2012-111736

Citation: Journal of Alzheimer's Disease, vol. 31, no. 3, pp. 669-676, 2012

Authors: Yang, Hongqian | Lyutvinskiy, Yaroslav | Herukka, Sanna-Kaisa | Soininen, Hilkka | Rutishauser, Dorothea | Zubarev, Roman A.

Article Type: Research Article

Abstract: Background: Patients with mild cognitive impairment (MCI) have varying risks of progression to Alzheimer’s disease (AD). Objective: To test the utility of the relative abundances of blood plasma polypeptides for predicting the risk of AD progression. Methods: 119 blood plasma samples of patients with MCI with different outcomes (stable MCI and progressive MCI) were analyzed by untargeted, label-free shotgun proteomics. Predictive biomarkers of progressive MCI were selected by multivariate analysis, followed by cross-validation of the predictive model. Results: The best model demonstrated the accuracy of ca. 79% in predicting progressive MCI. Sex differences of the predictive biomarkers were also assessed. …We have identified some sex-specific protein biomarkers, e.g., alpha-2-macrogloblin (A2M), which strongly correlates with female AD progression but not with males. Conclusion: Significant sex bias in AD-specific biomarkers underscores the necessity of selecting sex-balanced cohort in AD biomarker studies, or using sex-specific models. Blood protein biomarkers are found to be promising for predicting AD progression in clinical settings. Show more

Keywords: Biomarkers, human blood plasma, label-free quantification, mass spectrometry

DOI: 10.3233/JAD-132102

Citation: Journal of Alzheimer's Disease, vol. 40, no. 3, pp. 659-666, 2014