1.
Parrado-Fernández, Cristina, et al.
(författare)
Reduction of PINK1 or DJ-1 impair mitochondrial motility in neurites and alter ER-mitochondria contacts
2018
Ingår i: Journal of Cellular and Molecular Medicine (Print). - : Wiley. - 1582-1838 .- 1582-4934. ; 22:11, s. 5439-5449
Tidskriftsartikel (refereegranskat) abstract
Subcellular distribution of mitochondria in neurons is crucial for meeting the energetic demands, as well as the necessity to buffer Ca2+ within the axon, dendrites and synapses. Mitochondrial impairment is an important feature of Parkinson disease (PD), in which both familial parkinsonism genes DJ-1 and PINK1 have a great impact on mitochondrial function. We used differentiated human dopaminergic neuroblastoma cell lines with stable PINK1 or DJ-1 knockdown to study live motility of mitochondria in neurites. The frequency of anterograde and retrograde mitochondrial motility was decreased in PINK1 knockdown cells and the frequency of total mitochondrial motility events was reduced in both cell lines. However, neither the distribution nor the size of mitochondria in the neurites differed from the control cells even after downregulation of the mitochondrial fission protein, Drp1. Furthermore, mitochondria from PINK1 knockdown cells, in which motility was most impaired, had increased levels of GSK3 beta Ser9 and higher release of mitochondrial Ca2+ when exposed to CCCP-induced mitochondrial uncoupling. Further analysis of the ER-mitochondria contacts involved in Ca2+ shuttling showed that PINK1 knockdown cells had reduced contacts between the two organelles. Our results give new insight on how PINK1 and DJ-1 influence mitochondria, thus providing clues to novel PD therapies.
2.
Enache, Daniela, et al.
(författare)
CAIDE Dementia Risk Score and biomarkers of neurodegeneration in memory clinic patients without dementia
2016
Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 42, s. 124-131
Tidskriftsartikel (refereegranskat) abstract
The aim of this study was to explore cross-sectional associations between Cardiovascular Risk Factors, Aging and Dementia Study (CAIDE) Dementia Risk Score and dementia-related cerebrospinal fluid and neuroimaging biomarkers in 724 patients without dementia from the Memory Clinic at Karolinska University Hospital, Huddinge, Sweden. We additionally evaluated the score's capacity to predict dementia. Two risk score versions were calculated: one including age, gender, obesity, hyperlipidemia, and hypertension; and one additionally including apolipoprotein E (APOE) ε4 carrier status. Cerebrospinal fluid was analyzed for amyloid β (Aβ), total tau, and phosphorylated tau. Visual assessments of medial temporal lobe atrophy (MTA), global cortical atrophy-frontal subscale, and Fazekas scale for white matter changes (WMC) were performed. Higher CAIDE Dementia Risk Score (version without APOE) was significantly associated with higher total tau, more severe MTA, WMC, and global cortical atrophy-frontal subscale. Higher CAIDE Dementia Risk Score (version with APOE) was associated with reduced Aβ, more severe MTA, and WMC. CAIDE Dementia Risk Score version with APOE seemed to predict dementia better in this memory clinic population with short follow-up than the version without APOE.
3.
Holleman, Jasper, et al.
(författare)
Life-course stress, cognition, and diurnal cortisol in memory clinic patients without dementia
2024
Ingår i: Archives of gerontology and geriatrics (Print). - : Elsevier. - 0167-4943 .- 1872-6976. ; 119
Tidskriftsartikel (refereegranskat) abstract
AIMS: To examine associations of life-course stress with cognition and diurnal cortisol patterns in older adulthood, as well as potential mediation effects of diurnal cortisol patterns and perceived stress on the association between life-course stress and cognition.METHODS: 127 participants without dementia were selected from a cohort of Swedish memory clinic patients. Cross-sectional associations between scores on two chronic stress questionnaires (perceived stress, stressful life events (SLEs)), five cognitive domains (overall cognition, memory, working memory, processing speed, perceptual reasoning), and two measures of diurnal cortisol patterns (total daily output, diurnal cortisol slope), as well as potential mediation effects of diurnal cortisol patterns and perceived stress on associations between life-course stress and cognition, were assessed using linear regressions.RESULTS: Greater lifetime exposure to SLEs was associated with worse memory, working memory, and processing speed performance, but not with diurnal cortisol patterns. A greater number of SLEs in late childhood was associated with worse working memory and processing speed, while a greater number of SLEs in non-recent adulthood were associated with better overall cognition and perceptual reasoning. Greater perceived stress was associated with a flattened diurnal cortisol slope, but not with cognition. No evidence for interplay between self-reported and physiological stress markers was found in relation to cognition, although there appeared to be a significant positive indirect association between economic/legal SLEs and the diurnal cortisol slope via perceived stress.CONCLUSIONS: The associations between SLEs and cognition depend on the period during which SLEs occur, but seem independent of late-life cortisol dysregulation.
4.
Håkansson, Krister, 1952-, et al.
(författare)
BDNF Responses in Healthy Older Persons to 35 Minutes of Physical Exercise, Cognitive Training, and Mindfulness : Associations with Working Memory Function
2017
Ingår i: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 55:2, s. 645-657
Tidskriftsartikel (refereegranskat) abstract
Brain-derived neurotrophic factor (BDNF) has a central role in brain plasticity by mediating changes in cortical thickness and synaptic density in response to physical activity and environmental enrichment. Previous studies suggest that physical exercise can augment BDNF levels, both in serum and the brain, but no other study has examined how different types of activities compare with physical exercise in their ability to affect BDNF levels. By using a balanced cross over experimental design, we exposed nineteen healthy older adults to 35-minute sessions of physical exercise, cognitive training, and mindfulness practice, and compared the resulting changes in mature BDNF levels between the three activities. We show that a single bout of physical exercise has significantly larger impact on serum BDNF levels than either cognitive training or mindfulness practice in the same persons. This is the first study on immediate BDNF effects of physical activity in older healthy humans and also the first study to demonstrate an association between serum BDNF responsivity to acute physical exercise and working memory function. We conclude that the BDNF increase we found after physical exercise more probably has a peripheral than a central origin, but that the association between post-intervention BDNF levels and cognitive function could have implications for BDNF responsivity in serum as a potential marker of cognitive health.
5.
Miralbell, Julia, et al.
(författare)
Grey matter and cognitive patterns in cognitive impaired subjects using CSF biomarker cut-offs
2012
Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 29:4, s. 741-749
Tidskriftsartikel (refereegranskat) abstract
The aim of this study was to investigate brain tissue volumes, grey matter (GM) distribution, and cognitive performance for cognitively impaired subjects using cerebrospinal fluid (CSF) biomarker cut-offs as grouping criteria. 41 subjects attending the Memory Clinic, Karolinska University Hospital, Huddinge, Sweden, were divided into groups based on normal or abnormal CSF levels of Aβ1-42, t-tau, and p-tau181. SIENAX algorithms were employed for brain tissue volumes estimation and voxel-based morphometry (VBM) for mapping the differences in GM patterns. VBM revealed significant lower GM volumes in temporo-parietal, occipital, and prefrontal cortices for those subjects belonging to abnormal CSF t-tau and p-tau181 groups. No differences were found between groups according to CSF Aβ1-42 cut-offs. Patients with abnormal CSF p-tau181 showed lower cognitive performance compared to those with normal levels. Patients with abnormal levels of CSF tau (but not Aβ1-42) showed an Alzheimer's disease-like pattern for both GM distribution and cognitive profile, compared to those with normal levels. These results support the hypothesis that CSF t-tau or p-tau181 levels may be of direct value for the evaluation of disease severity.
6.
Ren, Yifei, et al.
(författare)
Multimorbidity, cognitive phenotypes, and Alzheimer's disease plasma biomarkers in older adults : A population-based study
2024
Ingår i: Alzheimer's & Dementia. - 1552-5260 .- 1552-5279. ; 20:3, s. 1550-1561
Tidskriftsartikel (refereegranskat) abstract
INTRODUCTION: To examine the burden and clusters of multimorbidity in association with mild cognitive impairment (MCI), dementia, and Alzheimer's disease (AD)-related plasma biomarkers among older adults.METHODS: This population-based study included 5432 participants (age ≥60 years); of these, plasma amyloid beta (Aβ), total tau, and neurofilament light chain (NfL) were measured in a subsample (n = 1412). We used hierarchical clustering to generate five multimorbidity clusters from 23 chronic diseases. We diagnosed dementia and MCI following international criteria. Data were analyzed using logistic and linear regression models.RESULTS: The number of chronic diseases was associated with dementia (multivariable-adjusted odds ratio = 1.22; 95% confidence interval [CI] = 1.11 to 1.33), AD (1.13; 1.01 to 1.26), vascular dementia (VaD) (1.44; 1.25 to 1.64), and non-amnestic MCI (1.25; 1.13 to 1.37). Metabolic cluster was associated with VaD and non-amnestic MCI, whereas degenerative ocular cluster was associated with AD (p < 0.05). The number of chronic diseases was associated with increased plasma Aβ and NfL (p < 0.05).DISCUSSION: Multimorbidity burden and clusters are differentially associated with subtypes of dementia and MCI and AD-related plasma biomarkers in older adults.
7.
Vaskivuo, Laura, et al.
(författare)
Associations between prospective and retrospective subjective memory complaints and neuropsychological performance in older adults : The finger study
2018
Ingår i: Journal of the International Neuropsychological Society. - : Cambridge University Press. - 1355-6177 .- 1469-7661. ; 24:10, s. 1099-1109
Tidskriftsartikel (refereegranskat) abstract
Objectives: Subjective memory complaints (SMCs) are among the key concerns in the elderly, but their role in detecting objective cognitive problems is unclear. The aim of this study was to clarify the association between SMCs (both prospective and retrospective memory complaints) and neuropsychological test performance in older adults at risk of cognitive decline. Methods: This investigation is part of the FINGER project, a multicenter randomized controlled trial aiming at preventing cognitive decline in high-risk individuals. The cognitive assessment of participants was conducted at baseline using a modified neuropsychological test battery (NTB). SMCs were evaluated with the Prospective and Retrospective Memory Questionnaire (PRMQ) in a sub-sample of 560 participants (mean age, 69.9 years). Results: Having more prospective SMCs was associated with slower processing speed, but not with other NTB domains. Retrospective SMCs were linked to poorer function on NTB total score, processing speed, and memory. Executive function domain was not associated with any PRMQ ratings. Depressive symptoms and poor quality of life diluted the observed associations for NTB total score and memory. However, the association between PRMQ and processing speed remained even after full adjustments. Conclusions: Our results indicate that self-reported memory problems, measured with PRMQ, are associated with objectively measured cognitive performance. Such complaints in healthy elderly people also seem to reflect reduced mental tempo, rather than memory deficits. Slowing of processing speed may thus be negatively related to memory self-efficacy. It is also important to consider affective factors among those who report memory problems.
8.
Vaskivuo, Laura, et al.
(författare)
Self and Informant Memory Reports in FINGER : Associations with Two-Year Cognitive Change
2019
Ingår i: Journal of Alzheimer's Disease. - : IOS PRESS. - 1387-2877 .- 1875-8908. ; 71:3, s. 785-795
Tidskriftsartikel (refereegranskat) abstract
Background: Subjective memory complaints (SMCs) may be the first sign of cognitive decline in aging. Objective: To examine whether SMCs reported by oneself and informant predict cognitive change over 2 years among at-risk elderly people, and to determine the relationship of different types of SMCs (prospective and retrospective memory complaints) and change in cognitive function. Methods: This investigation is part of the FINGER project, which is a multicenter randomized controlled trial aiming at preventing cognitive decline in cognitively healthy older adults with increased risk of dementia. A subsample of 303 controlgroup participants (aged 60-80 years) and their informants (n = 261) rated the frequency of SMCs, using the Prospective and Retrospective Memory Questionnaire (PRMQ). Cognitive performance was measured at baseline and at 1- and 2-year follow-up visits using a neuropsychological test battery. Results: Participants who reported more SMCs improved less in global cognition, executive function, and memory during the subsequent 2 years in the fully-adjusted analyses. Self-reported retrospective memory problems predicted less improvement in all cognitive domains, whereas prospective memory problems did not. Informant-reported memory problems were not linked to subsequent change in cognition. Conclusion: Our results indicate that self-reported SMCs, measured with PRMQ, predict future cognitive change in several cognitive domains. By contrast, reports by informants were not linked to changes in cognition. Among cognitively healthy at-risk elderly individuals, the persons themselves observe more easily problems relevant for their future cognitive trajectories than their informants.
9.
Vuorinen, Miika, et al.
(författare)
Changes in vascular factors 28 years from midlife and late-life cortical thickness
2013
Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 34:1, s. 100-109
Tidskriftsartikel (refereegranskat) abstract
We assessed midlife blood pressure (BP), body mass index, total cholesterol, and their changes over time in relation to cortical thickness on magnetic resonance imaging 28 years later in 63 elderly at risk of dementia. Participants in the population-based Cardiovascular Risk Factors, Aging, and Dementia study were first examined at midlife. A first follow-up was conducted after 21 years, and a second follow-up after an additional 7 years. Magnetic resonance images from the second follow-up were analyzed using algorithms developed at McGill University, Montreal, Canada. Midlife hypertension was related to thinner cortex in several brain areas, including insular, frontal, and temporal cortices. In elderly with thinner insular cortex, there was a continuous decline in systolic BP and an increase in pulse pressure after midlife, while in elderly with thicker insular cortex the decline in systolic BP started at older ages, paralleled by a decline in pulse pressure. No associations were found between body mass index, cholesterol, or apolipoprotein E ε4 allele and cortical thickness in this group of elderly at risk individuals.
10.
Vuorinen, Miika, et al.
(författare)
Changes in vascular risk factors from midlife to late life and white matter lesions : a 20-year follow-up study
2011
Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 31:2, s. 119-25
Tidskriftsartikel (refereegranskat) abstract
Background/Aims: This study investigated the relation of midlife blood pressure, total cholesterol, body mass index (BMI), their changes over time, apolipoprotein E, and white matter lesions (WML). Methods: Participants of the Cardiovascular Risk Factors, Aging and Incidence of Dementia study were derived from random, population-based samples previously surveyed in 1972, 1977, 1982 or 1987. In 1998, 1,449 (73%) individuals aged 65-79 years were re-examined (average follow-up 21 years). A subpopulation (n = 112) was scanned with a 1.5-tesla MRI scanner in 1998, and WML were assessed from fluid-attenuated inversion recovery images using a semi-quantitative visual rating scale. Results: Risk of late-life WML was related to midlife overweight (relative risk = 2.53; 95% CI = 1.70-2.89), obesity (2.94; 2.44-3.03), and hypertension (2.73; 1.81-3.08), even after adjustments for several confounding factors. Elevated BMI (>25) (2.26; 1.42-2.62) and hypertension (3.14; 1.83-3.40) from midlife to late life also increased the risk of WML. In addition, an association with WML was seen for decreasing blood pressure (hypertension at midlife but not at late life) (3.25; 2.46-3.41), even after controlling for antihypertensive treatment. Lipid-lowering drugs had a protective effect against WML (0.13; 0.020.59). Conclusions: These results indicate that early and sustained vascular risk factor control is associated with a lower likelihood of having more severe WML in late life.
