| 1. |
- Wang, Rui, et al.
(author)
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MRI load of cerebral microvascular lesions and neurodegeneration, cognitive decline, and dementia
- 2018
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In: Neurology. - 0028-3878 .- 1526-632X. ; 91:16, s. 1487-1497
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Journal article (peer-reviewed)abstract
- Objective To explore the differential associations of neurodegeneration and microvascular lesion load with cognitive decline and dementia in older people and the modifying effect of the APOE genotype on these associations. Methods A sample of 436 participants (age >= 60 years) was derived from the population-based Swedish National study on Aging and Care in Kungsholmen, Stockholm, and clinically examined at baseline (2001-2003) and 3 occasions during the 9-year follow-up. At baseline, we assessed microvascular lesion load using a summary score for MRI markers of lacunes, white matter hyperintensities (WMHs), and perivascular spaces and neurodegeneration load for markers of enlarged ventricles, smaller hippocampus, and smaller gray matter. We assessed cognitive function using the Mini-Mental State Examination (MMSE) test and diagnosed dementia following the Diagnostic and Statistical Manual of Mental Disorders, 4th edition criteria. We analyzed data using linear mixed-effects, mediation, and random-effects Cox models. Results During the follow-up, 46 participants were diagnosed with dementia. Per 1-point increase in microvascular lesion and neurodegeneration score (range 0-3) was associated with multiple adjusted beta-coefficients of -0.35 (95% confidence interval, -0.51 to -0.20) and -0.44 (-0.56 to -0.32), respectively, for the MMSE score and multiple adjusted hazard ratios of 1.68 (1.12-2.51) and 2.35 (1.58-3.52), respectively, for dementia; carrying APOE epsilon 4 reinforced the associations with MMSE decline. WMH volume changes during the follow-up mediated 66.9% and 12.7% of the total association of MMSE decline with the baseline microvascular score and neurodegeneration score, respectively. Conclusions Both cerebral microvascular lesion and neurodegeneration loads are strongly associated with cognitive decline and dementia. The cognitive decline due to microvascular lesions is exacerbated by APOE epsilon 4 and is largely attributed to progression and development of microvascular lesions.
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| 2. |
- Cedervall, Ylva, et al.
(author)
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Timed Up-and-Go Dual-Task Testing in the Assessment of Cognitive Function : A Mixed Methods Observational Study for Development of the UDDGait Protocol
- 2020
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In: International Journal of Environmental Research and Public Health. - : MDPI. - 1661-7827 .- 1660-4601. ; 17:5
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Journal article (peer-reviewed)abstract
- New methods to screen for and identify early-stage dementia disorders are highly sought after. The purpose of this pilot study is to develop a study protocol for a dual-task test aimed at aiding the early detection of dementia disorders. We used the Timed Up-and-Go (TUG) test, which is a mobility task involving starting in a sitting position, standing up, walking three meters to cross a line on the floor, turning around, walking back and sitting down again. We combined TUG with the verbal task of naming different animals. Pilot study participants were 43 individuals with and without established dementia diagnoses who attended a clinic for memory assessment. Video-recorded test performances were systematically analysed. Deviant test performances concerning the interplay between test administration and participants' responses to the assessment instructions were revealed and led to refinements being made to the final study protocol. Exploration of the dual-task test outcome measures in a sub-sample of 22 persons, ten with and twelve without dementia, indicated that step-length and number of named animals after the turning point of the dual-task test might constitute appropriate measures for examining this kind of sample. We concluded that the refined study protocol is feasible for testing individuals undergoing initial memory assessments and healthy controls. Follow-up studies with larger samples are being carried out and will bring new knowledge to this area of research. It may also provide an opportunity for further studies exploring possibilities for broad clinical implementation.
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| 3. |
- Liang, Yajun, et al.
(author)
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Migraine, Cognitive Decline, and Dementia in Older Adults : A Population-Based Study.
- 2022
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In: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 88:1, s. 263-271
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Journal article (peer-reviewed)abstract
- BACKGROUND: The potential impact of migraine on cognitive aging among older adults remains controversial.OBJECTIVE: To examine the relationship of migraine and subtypes with cognitive decline and dementia in an older Swedish population.METHODS: This population-based study included 3069 participants (age≥60) from the Swedish National study on Aging and Care in Kungsholmen, Stockholm. Baseline examination was conducted in 2001-2004, and participants were followed every 3 or 6 years until 2013-2016. Data were collected through face-to-face interviews, clinical examinations, laboratory tests, and linkage with registers. Global cognitive function was measured with the Mini-Mental State Examination (MMSE). Dementia was diagnosed according to the DSM-IV criteria. Migraine and subtypes were defined following the international classification system. Data were analyzed using logistic regression, Cox regression, and linear mixed-effects models.RESULTS: At baseline, 305 participants were defined with non-migraine headache and 352 with migraine. The cross-sectional analysis showed that the multivariable-adjusted odds ratio (95% confidence interval) of prevalent dementia was 0.49 (0.20-1.21) for migraine and 0.66 (0.26-1.66) for migraine without aura. The longitudinal analysis showed that the multivariable-adjusted hazard ratios of incident dementia associated with migraine and subtypes ranged 0.68-0.89 (p > 0.05). Furthermore, migraine and subtypes were not significantly associated with either baseline MMSE score or MMSE changes during follow-ups (p > 0.05). The nonsignificant associations did not vary substantially by age, APOEɛ4 allele, cerebrovascular disease, and antimigraine treatment (p for interactions > 0.05).CONCLUSION: This study shows no evidence supporting the associations of migraine and its subtypes with cognitive decline and dementia among older adults.
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| 4. |
- Olivo, G., et al.
(author)
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Immediate effects of a single session of physical exercise on cognition and cerebral blood flow: A randomized controlled study of older adults
- 2021
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In: Neuroimage. - : Elsevier BV. - 1053-8119 .- 1095-9572. ; 225
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Journal article (peer-reviewed)abstract
- Background: Regular physical activity is beneficial for cognitive performance in older age. A single bout of aerobic physical exercise can transiently improve cognitive performance. Researchers have advanced improvements in cerebral circulation as a mediator of long-term effects of aerobic physical exercise on cognition, but the immediate effects of exercise on cognition and cerebral perfusion are not well characterized and the effects in older adults are largely unknown. Methods: Forty-nine older adults were randomized to a 30-min aerobic exercise at moderate intensity or relaxation. Groups were matched on age and cardiovascular fitness (VO2 max). Average Grey Matter Blood Flow (GMBF), measured by a pulsed arterial-spin labeling (pASL) magnetic resonance imaging (MRI) acquisition, and working memory performance, measured by figurative n-back tasks with increasing loads were assessed before and 7 min after exercising/resting. Results: Accuracy on the n-back task increased from before to after exercising/resting regardless of the type of activity. GMBF decreased after exercise, relative to the control (resting) group. In the exercise group, higher n-back performance after exercise was associated with lower GMBF in the right hippocampus, left medial frontal cortex and right orbitofrontal cortex, and higher cardiovascular fitness was associated with lower GMBF. Conclusion: The decrease of GMBF reported in younger adults shortly after exercise also occurs in older adults and relates to cardiovascular fitness, potentially supporting the link between cardiovascular fitness and cerebrovascular reactivity in older age.
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| 5. |
- Gallagher, P, et al.
(author)
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Neurocognitive intra-individual variability in mood disorders : effects on attentional response time distributions.
- 2015
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In: Psychological Medicine. - 0033-2917 .- 1469-8978. ; 45:14, s. 2985-97
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Journal article (peer-reviewed)abstract
- BACKGROUND: Attentional impairment is a core cognitive feature of major depressive disorder (MDD) and bipolar disorder (BD). However, little is known of the characteristics of response time (RT) distributions from attentional tasks. This is crucial to furthering our understanding of the profile and extent of cognitive intra-individual variability (IIV) in mood disorders.METHOD: A computerized sustained attention task was administered to 138 healthy controls and 158 patients with a mood disorder: 86 euthymic BD, 33 depressed BD and 39 medication-free MDD patients. Measures of IIV, including individual standard deviation (iSD) and coefficient of variation (CoV), were derived for each participant. Ex-Gaussian (and Vincentile) analyses were used to characterize the RT distributions into three components: mu and sigma (mean and standard deviation of the Gaussian portion of the distribution) and tau (the 'slow tail' of the distribution).RESULTS: Compared with healthy controls, iSD was increased significantly in all patient samples. Due to minimal changes in average RT, CoV was only increased significantly in BD depressed patients. Ex-Gaussian modelling indicated a significant increase in tau in euthymic BD [Cohen's d = 0.39, 95% confidence interval (CI) 0.09-0.69, p = 0.011], and both sigma (d = 0.57, 95% CI 0.07-1.05, p = 0.025) and tau (d = 1.14, 95% CI 0.60-1.64, p < 0.0001) in depressed BD. The mu parameter did not differ from controls.CONCLUSIONS: Increased cognitive variability may be a core feature of mood disorders. This is the first demonstration of differences in attentional RT distribution parameters between MDD and BD, and BD depression and euthymia. These data highlight the utility of applying measures of IIV to characterize neurocognitive variability and the great potential for future application.
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| 6. |
- Gallo, Federico, et al.
(author)
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Cognitive Trajectories and Dementia Risk : A Comparison of Two Cognitive Reserve Measures.
- 2021
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In: Frontiers in Aging Neuroscience. - : Frontiers Media S.A.. - 1663-4365 .- 1663-4365. ; 13
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Journal article (peer-reviewed)abstract
- Background and Objectives: Cognitive reserve (CR) is meant to account for the mismatch between brain damage and cognitive decline or dementia. Generally, CR has been operationalized using proxy variables indicating exposure to enriching activities (activity-based CR). An alternative approach defines CR as residual variance in cognition, not explained by the brain status (residual-based CR). The aim of this study is to compare activity-based and residual-based CR measures in their association with cognitive trajectories and dementia. Furthermore, we seek to examine if the two measures modify the impact of brain integrity on cognitive trajectories and if they predict dementia incidence independent of brain status.Methods: We used data on 430 older adults aged 60+ from the Swedish National Study on Aging and Care in Kungsholmen, followed for 12 years. Residual-based reserve was computed from a regression predicting episodic memory with a brain-integrity index incorporating six structural neuroimaging markers (white-matter hyperintensities volume, whole-brain gray matter volume, hippocampal volume, lateral ventricular volume, lacunes, and perivascular spaces), age, and sex. Activity-based reserve incorporated education, work complexity, social network, and leisure activities. Cognition was assessed with a composite of perceptual speed, semantic memory, letter-, and category fluency. Dementia was clinically diagnosed in accordance with DSM-IV criteria. Linear mixed models were used for cognitive change analyses. Interactions tested if reserve measures modified the association between brain-integrity and cognitive change. Cox proportional hazard models, adjusted for brain-integrity index, assessed dementia risk.Results: Both reserve measures were associated with cognitive trajectories [β × time (top tertile, ref.: bottom tertile) = 0.013; 95% CI: -0.126, -0.004 (residual-based) and 0.011; 95% CI: -0.001, 0.024, (activity-based)]. Residual-based, but not activity-based reserve mitigated the impact of brain integrity on cognitive decline [β (top tertile × time × brain integrity) = -0.021; 95% CI: -0.043, 0.001] and predicted 12-year dementia incidence, after accounting for the brain-integrity status [HR (top tertile) = 0.23; 95% CI: 0.09, 0.58].Interpretation: The operationalization of reserve based on residual cognitive performance may represent a more direct measure of CR than an activity-based approach. Ultimately, the two models of CR serve largely different aims. Accounting for brain integrity is essential in any model of reserve.
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| 7. |
- Larsson, L. E., et al.
(author)
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Association of Sarcopenia and Its Defining Components with the Degree of Cognitive Impairment in a Memory Clinic Population
- 2023
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In: Journal of Alzheimer's Disease. - : IOS Press BV. - 1387-2877 .- 1875-8908. ; 96:2, s. 777-788
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Journal article (peer-reviewed)abstract
- Background: Sarcopenia and cognitive impairment are two leading causes of disabilities. Objective: The objective was to examine the prevalence of sarcopenia and investigate the association between sarcopenia diagnostic components (muscle strength, muscle mass, and physical performance) and cognitive impairment in memory clinic patients. Methods: 368 patients were included (age 59.0±7.25 years, women: 58.7%), displaying three clinical phenotypes of cognitive impairments, i.e., subjective cognitive impairment (SCI, 57%), mild cognitive impairment (MCI, 26%), and Alzheimer's disease (AD, 17%). Sarcopenia was defined according to diagnostic algorithm recommended by the European Working Group on Sarcopenia in Older People. Components of sarcopenia were grip strength, bioelectrical impedance analysis, and gait speed. They were further aggregated into a score (0-3 points) by counting the numbers of limited components. Multi-nominal logistic regression was applied. Results: Probable sarcopenia (i.e., reduced grip strength) was observed in 9.6% of the patients, and 3.5% were diagnosed with sarcopenia. Patients with faster gait speed showed less likelihood of MCI (odds ratio [OR]: 0.24, 95% confidence interval [CI]: 0.06-0.90) and AD (OR: 0.12, 95% CI: 0.03-0.60). One or more limited sarcopenia components was associated with worse cognitive function. After adjusting for potential confounders, the association remained significant only for AD (OR 4.29, 95% CI 1.45-11.92). Conclusion: The results indicate a connection between the sarcopenia components and cognitive impairments. Limitations in the sarcopenia measures, especially slow walking speed, were related to poorer cognitive outcomes. More investigationsare required to further verify the causal relationship between sarcopenia and cognitive outcomes.
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| 8. |
- Nilsson, Jonna, et al.
(author)
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Naming is not explaining : future directions for the cognitive reserve and brain maintenance theories
- 2018
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In: Alzheimer's Research & Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 10
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Research review (peer-reviewed)abstract
- Contemporary imaging measures of the human brain explain less than half of the differences in cognitive functioning and change among older adults. Researchers have advanced several theories and concepts to guide research that aims to better explain these individual differences in cognitive aging. Taking the fundamental measurement model in the empirical sciences as a starting point, we here scrutinize two such complementary theories, brain maintenance and cognitive reserve, in an attempt to clarify these theories, gauge their usefulness, and identify ways in which they can be further developed. We demonstrate that, although both theories are highly useful for spawning theorizing and empirical work, they can be further developed by detailing the theoretical and operational definitions of the concepts that they propose. We propose a few ways forward in these directions.
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| 9. |
- Wang, Rui, et al.
(author)
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Shared risk and protective factors between Alzheimer's disease and ischemic stroke : A population-based longitudinal study.
- 2021
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In: Alzheimer's & Dementia. - : John Wiley & Sons. - 1552-5260 .- 1552-5279. ; 17:2, s. 191-204
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Journal article (peer-reviewed)abstract
- INTRODUCTION: Stroke, especially ischemic stroke's (IS) link with Alzheimer's disease (AD) remains unclear.METHODS: This prospective cohort study included 2459 AD- and cerebrovascular disease-free older adults at baseline (mean age 71.9 ± 10.3 years, Stockholm, Sweden). Using Cox regressions, shared risk factors (SRFs) and shared protective factors (SPFs) between AD and IS were recognized when their hazard ratios in both AD and IS models were significant and in the same direction.RESULTS: During the follow-up period of up to 15 years, 132 AD and 260 IS mutually exclusive cases were identified. SRFs were low education, sedentary lifestyle, and heart diseases. High levels of psychological well-being, actively engaging in leisure activities, and a rich social network were SPFs. Having ≥1 SPF reduced 47% of AD and 28% of IS risk among people with a low risk profile (<2 SRFs), and 38% of AD and 31% of IS risk with a high risk profile (≥2 SRFs). In total, 57.8% of AD/IS cases could be prevented if individuals have ≥1 SPF and no SRF.DISCUSSION: AD and IS share risk/protective profiles, and SPFs seem to counteract the adverse effects of SRFs on both AD and IS.
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| 10. |
- Xia, Xin, et al.
(author)
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From Normal Cognition to Cognitive Impairment and Dementia : Impact of Orthostatic Hypotension.
- 2021
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In: Hypertension. - : Wolters Kluwer. - 0194-911X .- 1524-4563. ; 78:3, s. 769-778
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Journal article (peer-reviewed)abstract
- The role of orthostatic hypotension (OH) in the continuum of cognitive aging remains to be clarified. We sought to investigate the associations of OH with dementia, cognitive impairment, no dementia (CIND), and CIND progression to dementia in older adults while considering orthostatic symptoms. This population-based cohort study included 2532 baseline (2001–2004) dementia-free participants (age ≥60 years; 62.6% women) in the SNAC-K (Swedish National Study on Aging and Care in Kungsholmen) who were regularly examined over 12 years. We further divided the participants into a baseline CIND-free cohort and a CIND cohort. OH was defined as a decrease by ≥20/10 mmHg in systolic/diastolic blood pressure upon standing and further divided into asymptomatic and symptomatic OH. Dementia was diagnosed following the international criteria. CIND was defined as scoring ≥1.5 SDs below age group-specific means in ≥1 cognitive domain. Data were analyzed with flexible parametric survival models, controlling for confounding factors. Of the 2532 participants, 615 were defined with OH at baseline, and 322 were diagnosed with dementia during the entire follow-up period. OH was associated with an adjusted hazard ratio of 1.40 for dementia (95% CI, 1.10–1.76), 1.15 (0.94–1.40) for CIND, and 1.54 (1.05–2.25) for CIND progression to dementia. The associations of dementia and CIND progression to dementia with asymptomatic OH were similar to overall OH, whereas symptomatic OH was only associated with CIND progression to dementia. Our study suggests that OH, even asymptomatic OH, is associated with increased risk of dementia and accelerated progression from CIND to dementia in older adults.
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