| 1. |
- Ferreira, Daniel, et al.
(författare)
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The interactive effect of demographic and clinical factors on hippocampal volume : A multicohort study on 1958 cognitively normal individuals
- 2017
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Ingår i: Hippocampus. - : Wiley. - 1050-9631 .- 1098-1063. ; 27:6, s. 653-667
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease is characterized by hippocampal atrophy. Other factors also influence the hippocampal volume, but their interactive effect has not been investigated before in cognitively healthy individuals. The aim of this study is to evaluate the interactive effect of key demographic and clinical factors on hippocampal volume, in contrast to previous studies frequently investigating these factors in a separate manner. Also, to investigate how comparable the control groups from ADNI, AIBL, and AddNeuroMed are with five population-based cohorts. In this study, 1958 participants were included (100 AddNeuroMed, 226 ADNI, 155 AIBL, 59 BRC, 295 GENIC, 279 BioFiNDER, 398 PIVUS, and 446 SNAC-K). ANOVA and random forest were used for testing between-cohort differences in demographic-clinical variables. Multiple regression was used to study the influence of demographic-clinical variables on hippocampal volume. ANCOVA was used to analyze whether between-cohort differences in demographic-clinical variables explained between-cohort differences in hippocampal volume. Age and global brain atrophy were the most important variables in explaining variability in hippocampal volume. These variables were not only important themselves but also in interaction with gender, education, MMSE, and total intracranial volume. AddNeuroMed, ADNI, and AIBL differed from the population-based cohorts in several demographic-clinical variables that had a significant effect on hippocampal volume. Variability in hippocampal volume in individuals with normal cognition is high. Differences that previously tended to be related to disease mechanisms could also be partly explained by demographic and clinical factors independent from the disease. Furthermore, cognitively normal individuals especially from ADNI and AIBL are not representative of the general population. These findings may have important implications for future research and clinical trials, translating imaging biomarkers to the general population, and validating current diagnostic criteria for Alzheimer's disease and predementia stages.
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| 2. |
- Glans, Isabelle, et al.
(författare)
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Association Between Dietary Habits in Midlife With Dementia Incidence Over a 20-Year Period
- 2023
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Ingår i: Neurology. - : LIPPINCOTT WILLIAMS & WILKINS. - 0028-3878 .- 1526-632X. ; 100:1, s. E28-E37
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Tidskriftsartikel (refereegranskat)abstract
- Background and ObjectivesDementia cases are expected to triple during the next 30 years, highlighting the importance of finding modifiable risk factors for dementia. The aim of this study was to investigate whether adherence to conventional dietary recommendations or to a modified Mediterranean diet are associated with a subsequent lower risk of developing all-cause dementia, Alzheimer disease (AD), vascular dementia (VaD), or with future accumulation of AD-related beta-amyloid (A beta) pathology.MethodsBaseline examination in the prospective Swedish population-based Malmo Diet and Cancer Study took place in 1991-1996 with a follow-up for incident dementia until 2014. Nondemented individuals born 1923-1950 and living in Malmo were invited to participate. Thirty thousand four hundred forty-six were recruited (41% of all eligible). Twenty-eight thousand twenty-five had dietary data and were included in this study. Dietary habits were assessed with a 7-day food diary, detailed food frequency questionnaire, and 1-hour interview. Main outcomes were incident all-cause dementia, AD, or VaD determined by memory clinic physicians. Secondary outcome was A beta-accumulation measured using CSF A beta 42 (n = 738). Cox proportional hazard models were used to examine associations between diet and risk of developing dementia (adjusted for demographics, comorbidities, smoking, physical activity, and alcohol).ResultsSixty-one percent were women, and the mean (SD) age was 58.1 (7.6) years. One thousand nine hundred forty-three (6.9%) were diagnosed with dementia (median follow-up, 19.8 years). Individuals adhering to conventional dietary recommendations did not have lower risk of developing all-cause dementia (hazard ratio [HR] comparing worst with best adherence, 0.93, 95% CI 0.81-1.08), AD (HR 1.03, 0.85-1.23), or VaD (HR 0.93, 0.69-1.26). Neither did adherence to the modified Mediterranean diet lower the risk of developing all-cause dementia (HR 0.93 0.75-1.15), AD (HR 0.90, 0.68-1.19), or VaD (HR 1.00, 0.65-1.55). The results were similar when excluding participants developing dementia within 5 years or those with diabetes. No significant associations were found between diet and abnormal A beta accumulation, conventional recommendations (OR 1.28, 0.74-2.24) or modified Mediterranean diet (OR 0.85, 0.39-1.84).DiscussionIn this 20-year follow-up study, neither adherence to conventional dietary recommendations nor to modified Mediterranean diet were significantly associated with subsequent reduced risk for developing all-cause dementia, AD dementia, VaD, or AD pathology.
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| 3. |
- Glans, Isabelle, et al.
(författare)
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Associations of modifiable and non-modifiable risk factors with cognitive functions - a prospective, population-based, 17 years follow-up study of 3,229 individuals
- 2024
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Ingår i: Alzheimer's Research & Therapy. - : BMC. - 1758-9193. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Although several cardiovascular, demographic, genetic and lifestyle factors have been associated with cognitive function, little is known about what type of cognitive impairment they are associated with. The aim was to examine the associations between different risk factors and future memory and attention/executive functions, and their interaction with APOE genotype. Methods Participants from a large, prospective, population-based, Swedish study were included (n = 3,229). Linear regression models were used to examine baseline hypertension, body mass index (BMI), long-term glucose levels (HbA(1c)), different lipid levels, physical activity, alcohol consumption, smoking, education, APOE genotype, age and sex. All models were adjusted for follow-up time and basic demographics, and, in a second step, all significant predictors were included to examine independent effects. Follow-up outcomes were memory and attention/executive functions. Results The mean age at baseline was 56.1 (SD 5.7) years and 59.7% were women. The mean follow-up time was 17.4 (range 14.3-20.8) years. When examining independent effects, APOE epsilon 4 genotype(p < 0.01), and higher HbA(1c)(p < 0.001), were associated with future low memory function. Higher BMI (p < 0.05), and HbA(1c)(p < 0.05), lower high-density lipoprotein cholesterol (HDL-C)(p < 0.05)and stroke(p < 0.001) were associated with future low attention/executive function. The strongest factors associated with both better memory and attention/executive functions were higher education and alcohol consumption. Further, significant interaction effects between predictors and APOE genotype were found. For memory function, the protective effects of education were greater among epsilon 4-carriers(p < 0.05). For attention/executive function, the protective effects of alcohol were greater among epsilon 2 or epsilon 4-carriers(p < 0.05). Also, attention/executive function was lower among epsilon 4-carriers with higher BMI(p < 0.05) and epsilon 2-carriers with higher HbA1c-levels(p < 0.05). Conclusions Targeting cardiovascular risk factors in mid-life could have greater effect on future attention/executive functions rather than memory, whereas targeting diabetes could be beneficial for multiple cognitive domains. In addition, effects of different risk factors may vary depending on the APOE genotype. The varied cognitive profiles suggest that different mechanisms and brain regions are affected by the individual risk factors. Having detailed knowledge about the specific cognitive effects of different risk factors might be beneficial in preventive health counseling.
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| 4. |
- Gustavsson, Anna-Märta, et al.
(författare)
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Cerebral Microbleeds and White Matter Hyperintensities in Cognitively Healthy Elderly : A Cross-Sectional Cohort Study Evaluating the Effect of Arterial Stiffness
- 2015
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Ingår i: Central and Eastern European Migration Review. - : S. Karger. - 1664-5456 .- 2053-8871. ; 5:2, s. 41-51
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Arterial stiffness reflects the ageing processes in the vascular system, and studies have shown an association between reduced cognitive function and cerebral small vessel disease. Small vessel disease can be visualized as white matter hyperintensities (WMH) and lacunar infarcts but also as cerebral microbleeds on brain magnetic resonance imaging (MRI). We aimed to investigate if arterial stiffness influences the presence of microbleeds, WMH and cognitive function in a population of cognitively healthy elderly.METHODS: The study population is part of the Swedish BioFinder study and consisted of 208 individuals without any symptoms of cognitive impairment, who scored >27 points on the Mini-Mental State Examination. The participants (mean age, 72 years; 59% women) underwent MRI of the brain with visual rating of microbleeds and WMH. Arterial stiffness was measured with carotid-femoral pulse wave velocity (cfPWV). Eight cognitive tests covering different cognitive domains were performed.RESULTS: Microbleeds were detected in 12% and WMH in 31% of the participants. Mean (±standard deviation, SD) cfPWV was 10.0 (±2.0) m/s. There was no association between the presence of microbleeds and arterial stiffness. There was a positive association between arterial stiffness and WMH independent of age or sex (odds ratio, 1.58; 95% confidence interval, 1.04-2.40, p < 0.05), but the effect was attenuated when further adjustments for several cardiovascular risk factors were performed (p > 0.05). Cognitive performance was not associated with microbleeds, but individuals with WMH performed slightly worse than those without WMH on the Symbol Digit Modalities Test (mean ± SD, 35 ± 7.8 vs. 39 ± 8.1, p < 0.05). Linear regression revealed no direct associations between arterial stiffness and the results of the cognitive tests.CONCLUSIONS: Arterial stiffness was not associated with the presence of cerebral microbleeds or cognitive function in cognitively healthy elderly. However, arterial stiffness was related to the presence of WMH, but the association was attenuated when multiple adjustments were made. There was a weak negative association between WMH and performance in one specific test of attention. Longitudinal follow-up studies are needed to further assess the associations.
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| 5. |
- Gustavsson, Anna Märta, et al.
(författare)
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Midlife Atherosclerosis and Development of Alzheimer or Vascular Dementia
- 2020
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Ingår i: Annals of Neurology. - : John Wiley & Sons. - 0364-5134 .- 1531-8249. ; 87:1, s. 52-62
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate whether midlife atherosclerosis is associated with different dementia subtypes and related underlying pathologies.METHODS: Participants comprised the cardiovascular cohort of the Swedish prospective population-based Malmö Diet and Cancer Study (N = 6,103). Carotid plaques and intima media thickness (IMT) were measured at baseline (1991-1994). Dementia incidence until 2014 was obtained from national registers. Diagnoses were reviewed and validated in medical records. In a cognitively unimpaired subcohort (n = 330), β-amyloid42 and tau were quantified in cerebrospinal fluid (CSF), and white matter hyperintensity volume, lacunar infarcts, and cerebral microbleeds were estimated on magnetic resonance imaging (2009-2015).RESULTS: During 20 years of follow-up, 462 individuals developed dementia (mean age at baseline = 57.5 ± 5.9 years, 58% women). Higher IMT in midlife was associated with an increased hazard ratio (HR) of all-cause dementia (adjusted HR = 1.14 [95% confidence interval (CI) = 1.03-1.26]) and vascular dementia (adjusted HR = 1.32 [95% CI = 1.10-1.57]) but not Alzheimer disease (AD) dementia (adjusted HR = 0.95 [95% CI = 0.77-1.17]). Carotid plaques were associated with vascular dementia when assessed as a 3-graded score (adjusted HR = 1.90 [95% CI = 1.07-3.38]). In the cognitively unimpaired subcohort (53.8 ± 4.6 years at baseline, 60% women), higher IMT in midlife was associated with development of small vessel disease (adjusted odds ratio [OR] = 1.47 [95% CI = 1.05-2.06]) but not significantly with abnormal CSF AD biomarkers (adjusted OR = 1.28 [95% CI = 0.87-1.90] for Aβ42 and 1.35 [95% CI = 0.86-2.13] for Aβ42 /p-tau). Carotid plaques revealed no significant association with any of the underlying brain pathologies.INTERPRETATION: Our findings support an association between midlife atherosclerosis and development of vascular dementia and cerebral small vessel disease but not between atherosclerosis and subsequent AD dementia or AD pathology. ANN NEUROL 2019.
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| 6. |
- Nägga, Katarina, et al.
(författare)
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Increased midlife triglycerides predict brain β-amyloid and tau pathology 20 years later
- 2018
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Ingår i: Neurology. - : Lippincott Williams & Wilkins. - 0028-3878 .- 1526-632X. ; 90:1, s. e73-e81
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To evaluate the effect of midlife lipid levels on Alzheimer brain pathology 20 years later in cognitively normal elderly individuals.METHODS: This is a longitudinal cohort study of 318 cognitively normal individuals with data on fasting lipid levels at midlife (mean age 54 years). Presence of β-amyloid (Aβ) and tau pathologies 20 years later (mean age 73 years) were detected by quantifying Alzheimer disease (AD) biomarkers in CSF. In a subset (n = 134), Aβ (18F-flutemetamol) PET was also performed.RESULTS: CSF Aβ42 and Aβ PET revealed Aβ pathology in approximately 20% of the cognitively healthy population and CSF Aβ42/phosphorylated tau (p-tau) ratio indicated both Aβ and tau pathology in 16%. Higher levels of triglycerides in midlife were independently associated with abnormal CSF Aβ42 (odds ratio [OR] 1.34, 95% confidence interval [CI] 1.03-1.75, p = 0.029) and abnormal Aβ42/p-tau ratio (OR 1.46, 95% CI 1.10-1.93; p = 0.009) adjusting for age, sex, APOE ε4, education, and multiple vascular risk factors. Triglycerides were also associated with abnormal Aβ PET in multivariable regression models, but the association was attenuated in the fully adjusted model. Increased levels of medium and large low-density lipoprotein subfractions were significantly associated with abnormal Aβ PET and large high-density lipoprotein particles were associated with decreased risk of abnormal Aβ PET.CONCLUSIONS: Increased levels of triglycerides at midlife predict brain Aβ and tau pathology 20 years later in cognitively healthy individuals. Certain lipoprotein subfractions may also be risk factors for Aβ pathology. These findings further support an involvement of lipids in the very early stages of AD development.
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| 7. |
- Nägga, Katarina, et al.
(författare)
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Prevalence and Ascertainment of Dementia Cases in the Malmö Diet and Cancer Study
- 2022
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Ingår i: Journal of Alzheimer's Disease Reports. - : IOS Press. - 2542-4823. ; 6:1, s. 529-538
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Tidskriftsartikel (refereegranskat)abstract
- Background: Register diagnoses, both hospital-based and from open clinic care, are often used in research studies in Sweden. The validity of such diagnoses has been debated and a validation assessment can improve the diagnostic accuracy for use in research studies.Objective: The aim of this study was to investigate the quality of register-derived dementia diagnoses in the Malmö Diet and Cancer population study (MDCS) and to validate these diagnoses using systematic criteria.Methods: MDCS is a population-based prospective study comprising 30,446 participants. Register diagnoses of dementia for the MDCS population were derived from the Swedish National Patient Register (NPR) and validated through re-evaluation of available medical records by physicians.Results: In the MDCS cohort, 2,206 participants were diagnosed with dementia according to the NPR during a mean follow-up of 18.1 years. The general dementia diagnosis was valid in 96% of the cases, but 40% of the specific dementia diagnoses were changed during the process of reevaluation. The diagnostic validity varied between 25.2% and 82.9% for the different diagnoses. The results from the validity assessment per diagnostic category revealed that the validity of the NPR diagnoses was higher for the more specific diagnoses and lower for unspecified dementia. The major diagnostic shift during the re-evaluation was from unspecified dementia to more specific diagnoses.Conclusion: Validation of dementia diagnoses using medical records results in more precise diagnoses. Dementia diagnoses derived from registers should be validated in order to study associations between influential factors and different dementia diagnoses.
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| 8. |
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| 9. |
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| 10. |
- van Westen, Danielle, et al.
(författare)
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Cerebral white matter lesions - associations with A beta isoforms and amyloid PET
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6:20709
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Tidskriftsartikel (refereegranskat)abstract
- Small vessel disease (SVD) and amyloid deposition may promote each other, with a potential association between SVD and altered production or clearance of beta-amyloid (A beta) affecting its cleavage products. We investigated the relationship between SVD, multiple isoforms of A beta in cerebrospinal fluid (CSF) and cortical A beta in 831 subjects with cognitive performance ranging from normal to Alzheimer's disease (AD) (the Swedish BioFINDER study). SVD was estimated as white matter lesions (WML) and lacunes. 18F-flutemetamol PET was performed in 321 subjects. Lower CSF levels of A beta 38 and A beta 40 were consistently associated with increased WML in all subgroups, while lower levels of CSF A beta 42 were associated with WML mainly in AD. CSF A beta 38 and A beta 40 were associated with regional WML in all regions, while CSF A beta 42 was associated with temporal WML only. A composite measure of 18F-flutemetamol uptake was not associated with WML, and regional 18F-flutemetamol uptake only with temporal WML. Lacunes were not associated with A beta isoforms nor 18F-flutemetamol uptake. Our results suggest that WML may be associated with alterations in the production or clearance of A beta species, particularly of A beta 38 and A beta 40. However, in AD cases, A beta 42 pathology might be associated with WML, especially in the temporal lobe.
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