| 1. |
- Farnsworth von Cederwald, Bryn, et al.
(författare)
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Association of cardiovascular risk trajectory with cognitive decline and incident dementia
- 2022
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Ingår i: Neurology. - : Wolters Kluwer. - 0028-3878 .- 1526-632X. ; 98:20, s. e2013-e2022
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objectives: Cardiovascular risk factors have a recently established association with cognitive decline and dementia, yet most studies examine this association through cross-sectional data, precluding an understanding of the longitudinal dynamics of such risk. The current study aims to explore how the ongoing trajectory of cardiovascular risk affects subsequent dementia and memory decline risk. We hypothesize that an accelerated, long-term accumulation of cardiovascular risk, as determined by the Framingham Risk Score (FRS), will be more detrimental to cognitive and dementia state outcomes than a stable cardiovascular risk.Methods: We assessed an initially healthy, community-dwelling sample recruited from the prospective cohort Betula study. Cardiovascular disease risk, as assessed by the FRS, episodic memory performance, and dementia status were measured at each 5-year time point (T) across 20 to 25 years. Analysis was performed with bayesian additive regression tree, a semiparametric machine-learning method, applied herein as a multistate survival analysis method.Results: Of the 1,244 participants, cardiovascular risk increased moderately over time in 60% of sample, with observations of an accelerated increase in 18% of individuals and minimal change in 22% of individuals. An accelerated, as opposed to a stable, cardiovascular risk trajectory predicted an increased risk of developing Alzheimer disease dementia (average risk ratio [RR] 3.3–5.7, 95% CI 2.6–17.5 at T2, 1.9–6.7 at T5) or vascular dementia (average RR 3.3–4.1, 95% CI 1.1–16.6 at T2, 1.5–7.6 at T5) and was associated with an increased risk of memory decline (average RR 1.4–1.2, 95% CI 1–1.9 at T2, 1–1.5 at T5). A stable cardiovascular risk trajectory appeared to partially mitigate Alzheimer disease dementia risk for APOE ε4 carriers.Discussion: The findings of the current study show that the longitudinal, cumulative trajectory of cardiovascular risk is predictive of dementia risk and associated with the emergence of memory decline. As a result, clinical practice may benefit from directing interventions at individuals with accelerating cardiovascular risk.
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| 2. |
- Karalija, Nina, 1984-, et al.
(författare)
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Longitudinal Dopamine D2 Receptor Changes and Cerebrovascular Health in Aging
- 2022
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Ingår i: Neurology. - 1526-632X .- 0028-3878. ; 99
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVES: Cross-sectional studies suggest marked dopamine (DA) decline in aging, but longitudinal evidence is lacking. The aim of this study was to estimate within-person decline rates for DA D2-like receptors (DRD2) in aging and examine factors that may contribute to individual differences in DRD2 decline rates. METHODS: We investigated 5-year within-person changes in DRD2 availability in a sample of older adults. At both occasions, PET with 11C-raclopride and MRI were used to measure DRD2 availability in conjunction with structural and vascular brain integrity. RESULTS: Longitudinal analyses of the sample (baseline: n = 181, ages: 64-68 years, 100 men and 81 women; 5-year follow-up: n = 129, 69 men and 60 women) revealed aging-related striatal and extrastriatal DRD2 decline, along with marked individual differences in rates of change. Notably, the magnitude of striatal DRD2 decline was ∼50% of past cross-sectional estimates, suggesting that the DRD2 decline rate has been overestimated in past cross-sectional studies. Significant DRD2 reductions were also observed in select extrastriatal regions, including hippocampus, orbitofrontal cortex (OFC), and anterior cingulate cortex (ACC). Distinct profiles of correlated DRD2 changes were found across several associative regions (ACC, dorsal striatum, and hippocampus) and in the reward circuit (nucleus accumbens and OFC). DRD2 losses in associative regions were associated with white matter lesion progression, whereas DRD2 losses in limbic regions were related to reduced cortical perfusion. DISCUSSION: These findings provide the first longitudinal evidence for individual and region-specific differences of DRD2 decline in older age and support the hypothesis that cerebrovascular factors are linked to age-related dopaminergic decline.
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| 3. |
- Persson, J, et al.
(författare)
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Altered brain white-matter integrity in non-demented carriers of the APOE ε4 allele: A risk for Alzheimer’s disease.
- 2006
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Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 66:7, s. 1029-1033
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Tidskriftsartikel (refereegranskat)abstract
- Previous research has shown that polymorphisms of the apolipoprotein E (APOE) represent genetic risk factors for dementia and for cognitive impairment in the elderly. The neural mechanisms by which these genetic variations influence behavioral performance or clinical severity are not well understood. We used diffusion tensor imaging to investigate ultrastructural properties in brain white-matter to detect pathological processes that modify tissue integrity. Sixty participants were included in the study of which 30 were homozygous for the APOE ε3 allele, 10 were homozygous for the APOE ε4 allele, and 20 had the APOE ε34 allele combination. All individuals were non-demented, and the groups were matched on demographic variables and cognitive performance. The results showed a decline in fractional anisotropy, a marker for white-matter integrity, in the posterior corpus callosum of ε4 carriers compared to non-carriers. Additional sites of altered white-matter integrity included the medial temporal lobe. Conclusions: Although the mechanism underlying vulnerability of white matter tracts in APOE ε4 carriers is still unknown, our findings suggest that increased genetic risk for developing AD is associated with changes in microscopic white-matter integrity well before the onset of dementia.
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| 4. |
- Vilaplana, Eduard, et al.
(författare)
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Cortical microstructural correlates of astrocytosis in autosomal-dominant Alzheimer disease
- 2020
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Ingår i: Neurology. - : LIPPINCOTT WILLIAMS & WILKINS. - 0028-3878 .- 1526-632X. ; 94:19, s. e2026-E2036
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To study the macrostructural and microstructural MRI correlates of brain astrocytosis, measured with C-11-deuterium-L-deprenyl (C-11-DED)-PET, in familial autosomal-dominant Alzheimer disease (ADAD).Methods: The total sample (n = 31) comprised ADAD mutation carriers (n = 10 presymptomatic, 39.2 10.6 years old; n = 3 symptomatic, 55.5 2.0 years old) and noncarriers (n = 18, 44.0 +/- 13.7 years old) belonging to families with mutations in either the presenilin-1 or amyloid precursor protein genes. All participants underwent structural and diffusion MRI and neuropsychological assessment, and 20 participants (6 presymptomatic and 3 symptomatic mutation carriers and 11 noncarriers) also underwent C-11-DED-PET.Results: Vertex-wise interaction analyses revealed a differential relationship between carriers and noncarriers in the association between C-11-DED binding and estimated years to onset (EYO) and between cortical mean diffusivity (MD) and EYO. These differences were due to higher C-11-DED binding in presymptomatic carriers, with lower binding in symptomatic carriers compared to noncarriers, and to lower cortical MD in presymptomatic carriers, with higher MD in symptomatic carriers compared to noncarriers. Using a vertex-wise local correlation approach, C-11-DED binding was negatively correlated with cortical MD and positively correlated with cortical thickness.Conclusions: Our proof-of-concept study is the first to show that microstructural and macrostructural changes can reflect underlying neuroinflammatory mechanisms in early stages of Alzheimer disease (AD). The findings support a role for neuroinflammation in AD pathogenesis, with potential implications for the correct interpretation of neuroimaging biomarkers as surrogate endpoints in clinical trials.
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| 5. |
- Xu, W. L., et al.
(författare)
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Midlife overweight and obesity increase late-life dementia risk : a population-based twin study
- 2011
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Ingår i: Neurology. - 0028-3878 .- 1526-632X. ; 76:18, s. 1568-1574
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The relation of overweight to dementia is controversial. We aimed to examine the association of midlife overweight and obesity with dementia, Alzheimer disease (AD), and vascular dementia (VaD) in late life, and to verify the hypothesis that genetic and early-life environmental factors contribute to the observed association.Methods: From the Swedish Twin Registry, 8,534 twin individuals aged ≥65 (mean age 74.4) were assessed to detect dementia cases (DSM-IV criteria). Height and weight at midlife (mean age 43.4) were available in the Registry. Data were analyzed as follows: 1) unmatched case-control analysis for all twins using generalized estimating equation (GEE) models and 2) cotwin matched case-control approach for dementia-discordant twin pairs by conditional logistic regression taking into account lifespan vascular disorders and diabetes.Results: Among all participants, dementia was diagnosed in 350 subjects, and 114 persons had questionable dementia. Overweight (body mass index [BMI] >25-30) and obesity (BMI >30) at midlife were present in 2,541 (29.8%) individuals. In fully adjusted GEE models, compared with normal BMI (20-25), overweight and obesity at midlife were related to dementia with odds ratios (ORs) (95% CIs) of 1.71 (1.30-2.25) and 3.88 (2.12-7.11), respectively. Conditional logistic regression analysis in 137 dementia-discordant twin pairs led to an attenuated midlife BMI-dementia association. The difference in ORs from the GEE and the matched case-control analysis was statistically significant (p = 0.019).Conclusions: Both overweight and obesity at midlife independently increase the risk of dementia, AD, and VaD. Genetic and early-life environmental factors may contribute to the midlife high adiposity-dementia association.
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| 6. |
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| 7. |
- Johansson, Boo, et al.
(författare)
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Sensitivity and specificity of dementia coding in two Swedish disease registries
- 2004
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Ingår i: Neurology. - 0028-3878. ; 63:4, s. 739-41
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Tidskriftsartikel (refereegranskat)abstract
- The authors investigated the sensitivity and specificity of dementia identification in two Swedish disease registries by using clinical diagnoses from two population-based studies as gold standards. The probability of dementia detected by the Inpatient Discharge Registry was 55% for prevalent patients and 31% for incident patients and was higher than detection by the Cause of Death Registry. Specificity was 98% for the Inpatient Discharge Registry and 100% for the Cause of Death Registry.
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| 8. |
- Sacuicu, S, et al.
(författare)
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Prodromal cognitive signs of dementia in 85-year-olds using four sources of information
- 2005
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Ingår i: Neurology. - 0028-3878. ; 65:12, s. 1894-1900
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Tidskriftsartikel (refereegranskat)abstract
- The objective was to evaluate the utility of assessing four cognitive domains ob-tained from four information sources to identify individuals at risk for developing dementia, Alzheimer disease (AD), and vascular dementia (VaD). METHODS: A representative population sample of nondemented 85-year-olds (n = 313) from Gothenburg, Sweden, was examined regarding memory, language, and visuospa-tial and executive functions, using self- and key informant reports and neuropsy-chiatric and psychometric examinations. The sample was followed 3 years for in-cident dementia, AD, or possible VaD. RESULTS: All cases of dementia, AD, and VaD were preceded by low performance in most domains irrespective of informa-tion source. Isolated low memory performance or low cognitive performance with unimpaired memory did not predict dementia. Positive predictive values in-creased with number of domains affected. Self- and key informant reports were less useful for predicting dementia than neuropsychiatric and psychometric ex-aminations. The best positive predictive value (88%) was for low cognitive per-formance in all domains using neuropsychiatric and psychometric examinations; however, sensitivity was only 18%. CONCLUSIONS: Although memory impair-ment was necessary to predict dementia, it was not sufficient. Other cognitive domains needed to be affected. Relying on self-reports or key informants for early detection of dementia excluded a large group at risk. In addition, vascular de-mentia appeared to have a prodromal stage.
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| 9. |
- Sacuiu, Simona, 1971, et al.
(författare)
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Secular changes in cognitive predictors of dementia and mortality in 70-year-olds.
- 2010
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Ingår i: Neurology. - 1526-632X. ; 75:9, s. 779-85
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Successive elderly birth cohorts improved in cognitive performance during the 20th century. It is not clear whether this influences cognitive predictors of dementia and mortality. OBJECTIVE: In 2 longitudinal population studies, representing 2 cohorts of 70-year-olds examined 30 years apart, we investigated the relation between baseline cognitive function and 5-year occurrence of dementia and mortality. METHODS: Two representative cohorts of 70-year-olds initially free from dementia born in 1901-1902 (cohort 1901-1902: n = 381) and 1930 (cohort 1930: n = 551) from Gothenburg, Sweden, were examined in 1971-1972 and 2000-2001 and after 5 years for the outcome of dementia and death. Recent memory was evaluated during psychiatric examinations, and nonmemory domains using psychometric tests. RESULTS: At age 70, cohort 1930 performed better on psychometric tests, and had fewer recent memory problems compared to cohort 1901-1902. During 5-year follow-up, 5.0% in cohort 1901-1902 and 4.4% in cohort 1930 (p = 0.742) developed dementia, and 15.7% in cohort 1901-1902 and 4.4% in cohort 1930 died (p < 0.001). Recent memory was associated with incident dementia in both cohorts. Low scores in nonmemory tests were associated with incident dementia in cohort 1901-1902, but not in cohort 1930. Recent memory problems and lower scores in nonmemory tests were associated with 5-year mortality in cohort 1901-1902, but not in cohort 1930. CONCLUSIONS: Secular changes in cognitive performance may influence cognitive predictors of dementia and mortality, despite similar incidence of dementia. The findings should be taken cautiously due to differences between cohorts in refusal rates, quality of education, and dementia recognition in medical records.
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