| 61. |
- Garcia-Ptacek, Sara, et al.
(författare)
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Mortality Risk after Dementia Diagnosis by Dementia Type and Underlying Factors : A Cohort of 15,209 Patients based on the Swedish Dementia Registry
- 2014
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 41:2, s. 467-477
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Tidskriftsartikel (refereegranskat)abstract
- Background: Knowledge on survival in dementia is crucial for patients and public health planning. Most studies comparing mortality risk included few different dementia diagnoses. Objectives: To compare mortality risk in the most frequent dementia disorders in a large cohort of patients with an incident diagnosis, adjusting for potential confounding factors. Methods: 15,209 patients with dementia from the national quality database, Swedish Dementia Registry (SveDem), diagnosed in memory clinics from 2008 to 2011, were included in this study. The impact of age, gender, dementia diagnosis, baseline Mini-Mental State Examination (MMSE), institutionalization, coresidency, and medication on survival after diagnosis were examined using adjusted hazard ratios (HR) with 95% confidence intervals (CI). Results: During a mean follow-up of 2.5 years, 4,287 deaths occurred, with 114 (95% CI 111-117) deaths/1,000 person-years. Adjusted HR of death for men was 1.56 (95% CI 1.46-1.66) compared to women. Low MMSE, institutionalization, and higher number of medications were associated with higher HR of death. All dementia diagnoses demonstrated higher HR compared to Alzheimer's disease, with vascular dementia presenting the highest crude HR. After adjusting, frontotemporal dementia had the highest risk with a HR of 1.91 (95% CI 1.52-2.39), followed by Lewy body dementia (HR 1.64; 95% CI 1.39-1.95), vascular dementia (HR 1.55; 95% CI 1.42-1.69), Parkinson's disease dementia (HR 1.47; 95% CI 1.17-1.84), and mixed Alzheimer's disease and vascular dementia (HR 1.32; 95% CI 1.22-1.44). Conclusion: Worse cognition, male gender, higher number of medications, institutionalization, and age were associated with increased death risk after dementia diagnosis. Adjusted risk was lowest in Alzheimer's disease patients and highest in frontotemporal dementia subjects.
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| 62. |
- Ghani, Zartashia, 1980-, et al.
(författare)
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Short Term Economic Evaluation of the Digital Platform "Support, Monitoring and Reminder Technology for Mild Dementia" (SMART4MD) for People with Mild Cognitive Impairment and their Informal Caregivers
- 2022
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Ingår i: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 86:4, s. 1629-1641
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Tidskriftsartikel (refereegranskat)abstract
- Background: A randomized controlled trial of the SMART4MD tablet application was conducted for persons with mild cognitive impairment (PwMCI) and their informal caregivers to improve or maintain quality of life. Objective: The objective was to conduct economic evaluation of SMART4MD compared to standard care in Sweden from a healthcare provider perspective based on a 6-month follow-up period. Methods: Three hundred forty-five dyads were enrolled: 173 dyads in the intervention group and 172 in standard care. The primary outcome measures for PwMCI and informal caregivers were quality-adjusted life years (QALY). The results are presented as incremental cost-effectiveness ratios, and confidence intervals are calculated using non-parametric bootstrap procedure. Results: For PwMCI, the mean difference in total costs between intervention and standard care was (sic)12 (95%CI: -2090 to 2115) (US$ =(sic) 1.19) and the mean QALY change was -0.004 (95%CI: -0.009 to 0.002). For informal caregivers, the cost difference was -(sic)539 (95%CI: -2624 to 1545) and 0.003 (95%CI: -0.002 to 0.008) for QALY. The difference in cost and QALY for PwMCI and informal caregivers combined was -(sic)527 (95%CI: -3621 to 2568) and -0.001 (95%CI: -0.008 to 0.006). Although generally insignificant differences, this indicates that SMART4MD, compared to standard care was: 1) more costly and less effective for PwMCI, 2) less costly and more effective for informal caregivers, and 3) less costly and less effective for PwMCI and informal caregivers combined. Conclusion: The cost-effectiveness of SMART4MD over 6 months is inconclusive, although the intervention might be more beneficial for informal caregivers than PwMCI.
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| 63. |
- Giannakopoulos, Panteleimon, et al.
(författare)
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Personality Impact on Alzheimer's Disease - Signature and Vascular Imaging Markers : A PET-MRI Study
- 2022
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Ingår i: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 85:4, s. 1807-1817
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Tidskriftsartikel (refereegranskat)abstract
- Background: Several studies postulated that personality is an independent determinant of cognitive trajectories in old age. Objective: This study explores the impact of personality on widely used Alzheimer's disease (AD) and vascular imaging markers. Methods: We examined the association between personality and three classical AD imaging markers (centiloid-based-amyloid load, MRI volumetry in hippocampus, and media temporal lobe atrophy), and two vascular MRI parameters (Fazekas score and number of cortical microbleeds) assessed at baseline and upon a 54-month-follow-up. Personality was assessed with the Neuroticism Extraversion Openness Personality Inventory-Revised. Regression models were used to identify predictors of imaging markers including sex, personality factors, presence of APOE epsilon 4 allele and cognitive evolution over time. Results: Cortical GM volumes were negatively associated with higher levels of Conscientiousness both at baseline and follow-up. In contrast, higher scores of Openness were related to better preservation of left hippocampal volumes in these two time points and negatively associated with medial temporal atrophy at baseline. Amyloid load was not affected by personality factors. Cases with higher Extraversion scores displayed higher numbers of cortical microbleeds at baseline. Conclusion: Personality impact on brain morphometry is detected only in some among the routinely used imaging markers. The most robust associations concern the positive role of high levels of Conscientiousness and Openness on AD-signature MRI markers. Higher extraversion levels are associated with increased vulnerability to cortical microbleeds pointing to the fact that the socially favorable traits may have a detrimental effect on brain integrity in old age.
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| 64. |
- Gil-Bea, Francisco J, et al.
(författare)
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Insulin levels are decreased in the cerebrospinal fluid of women with prodomal Alzheimer's disease
- 2010
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Ingår i: Journal of Alzheimer's Disease. - Amsterdam; Washington : IOS Press. - 1387-2877 .- 1875-8908. ; 22:2, s. 405-413
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies have failed to reach consensus on insulin levels in cerebrospinal fluid of Alzheimer's disease (AD) patients and on its relation to pathological features. We performed a new analysis in patients at different stages of AD, and investigated the relationship of insulin levels with biochemical disease markers and with cognitive score. We included 99 patients from our Memory Clinic (Karolinska University Hospital, Sweden), including: 27 patients with mild AD, 13 that progressed from mild cognitive impairment (MCI) to AD in two years time, 26 with MCI stable after two years, and 33 with subjective cognitive impairment. Insulin was significantly decreased in the cerebrospinal fluid of both women and men with mild AD. Insulin deficits were seen in women belonging to both MCI groups, suggesting that this occurs earlier than in men. Insulin was positively associated with amyloid-β 1-42 (Aβ1-42) levels and cognitive score. Furthermore, total-tau/(Aβ1-42*insulin) ratio showed strikingly better sensitivity and specificity than the total-tau/Aβ1-42 ratio for early AD diagnosis in women.
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| 65. |
- Goumidi, Louisa, et al.
(författare)
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Study of estrogen receptor-α and receptor-β gene polymorphisms on Alzheimer's disease.
- 2011
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 26:3, s. 431-9
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Tidskriftsartikel (refereegranskat)abstract
- Estrogen treatment can modulate the risk for developing dementia in women. Therefore, single nucleotide polymorphisms (SNPs) in the estrogen receptor genes may constitute genetic susceptibility factors to Alzheimer's disease (AD). Thus, we investigated the impact of the genetic variability of the estrogen receptor α 1 (ESR1) and estrogen receptor α 2 (ESR2) genes on late onset AD risk. We analyzed 39 SNPs in ESR1 and 5 SNPs in ESR2 in a French case-control study of sporadic AD (1007 cases/647 controls). Individuals carrying the minor allele of rs7450824 had a lower risk of AD than homozygous subjects for the major allele (age, gender, and APOE ε4 allele adjusted odds ratio = 0.71 [0.57-0.89], p = 0.003). However, this association did not resist Bonferroni correction for multiple testing (p-threshold < 0.001). Consistently, no significant association could be detected when considering age of onset. We also tested for possible interactions between the ESR SNPs and APOE status (ε4 allele) or gender but no significant interaction could be observed. Even after stratifying the sample on APOE status or gender, no significant association with AD risk could be detected. Finally, we searched for potential gene-gene interactions between ESR1 and ESR2 SNPs but no significant interaction could be detected. Our results reinforce the notion that SNPs in the ESR1 or ESR2 genes do not seem to play a major role in the genetic susceptibility of AD.
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| 66. |
- Grande, Giulia, et al.
(författare)
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Long-Term Exposure to PM2.5 and Cognitive Decline : A Longitudinal Population-Based Study
- 2021
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 80:2, s. 591-599
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Tidskriftsartikel (refereegranskat)abstract
- Background: A growing but contrasting evidence relates air pollution to cognitive decline. The role of cerebrovascular diseases in amplifying this risk is unclear.Objectives: 1) Investigate the association between long-term exposure to air pollution and cognitive decline; 2) Test whether cerebrovascular diseases amplify this association.Methods: We examined 2,253 participants of the Swedish National study on Aging and Care in Kungsholmen (SNAC-K). One major air pollutant (particulate matter ≤2.5μm, PM2.5) was assessed yearly from 1990, using dispersion models for outdoor levels at residential addresses. The speed of cognitive decline (Mini-Mental State Examination, MMSE) was estimated as the rate of MMSE decline (linear mixed models) and further dichotomized into the upper (25%fastest cognitive decline), versus the three lower quartiles. The cognitive scores were used to calculate the odds of fast cognitive decline per levels of PM2.5 using regression models and considering linear and restricted cubic splines of 10 years exposure before the baseline. The potential modifier effect of cerebrovascular diseases was tested by adding an interaction term in the model.Results: We observed an inverted U-shape relationship between PM2.5 and cognitive decline. The multi-adjusted piecewise regression model showed an increased OR of fast cognitive decline of 81%(95%CI = 1.2–3.2) per interquartile range difference up to mean PM2.5 level (8.6μg/m3) for individuals older than 80. Above such level we observed no further risk increase (OR = 0.89;95%CI = 0.74–1.06). The presence of cerebrovascular diseases further increased such risk by 6%.Conclusion: Low to mean PM2.5 levels were associated with higher risk of accelerated cognitive decline. Cerebrovascular diseases further amplified such risk.
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| 67. |
- Gu, Gucci Jijuan, 1984-, et al.
(författare)
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Elevated MARK2-Dependent Phosphorylation of Tau in Alzheimer's Disease
- 2013
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 33:3, s. 699-713
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Tidskriftsartikel (refereegranskat)abstract
- The appearance of neurofibrillary tangles (NFT), one of the major hallmarks of Alzheimer's disease (AD), is most likely caused by inappropriate phosphorylation and/or dephosphorylation of tau, eventually leading to the accumulation of NFTs. Enhanced phosphorylation of tau on Ser(262) is detected early in the course of the disease and may have a role in the formation of tangles. Several kinases such as microtubule-affinity regulating kinase (MARK), protein kinase A, calcium calmodulin kinase II, and checkpoint kinase 2 are known to phosphorylate tau on Ser(262) in vitro. In this study, we took advantage of the in situ proximity ligation assay to investigate the role of MARK2, one of the four MARK isoforms, in AD. We demonstrate that MARK2 interacts with tau and phosphorylates tau at Ser(262) in stably transfected NIH/3T3 cells expressing human recombinant tau. Staurosporine, a protein kinase inhibitor, significantly reduced the interaction between MARK2 and tau, and also phosphorylation of tau at Ser(262). Furthermore, we observed elevated interactions between MARK2 and tau in post-mortem human AD brains, compared to samples from non-demented elderly controls. Our results from transfected cells demonstrate a specific interaction between MARK2 and tau, as well as MARK2-dependent phosphorylation of tau at Ser(262). Furthermore, the elevated interactions between MARK2 and tau in AD brain sections suggests that MARK2 may play an important role in early phosphorylation of tau in AD, possibly qualifying as a therapeutic target for intervention to prevent disease progression.
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| 68. |
- Gustafson, Deborah, 1966
(författare)
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Adiposity and Cognitive Decline: Underlying Mechanisms
- 2012
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Ingår i: Journal of Alzheimers Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 30:Supplement 2, s. S97-S112
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Tidskriftsartikel (refereegranskat)abstract
- Level of adiposity is linked to manifest dementia and Alzheimer's disease in epidemiological studies. Overweight and obesity in mid- and late-life may increase risk for dementia, whereas decline in body weight or body mass index and underweight in years preceding and at the time of a dementia diagnosis may also relate to dementia. The role of adiposity during the period of cognitive decline is, as yet, not understood; however, some hypotheses relating adipose tissue to brain can be drawn. This review focuses on potential, varied mechanisms whereby adipose tissue may influence or interact with the brain and/or dementia risk during the dynamic period of life characterized by both body weight and cognitive decline. These mechanisms relate to: a) adipose tissue location and cell types, b) body composition, c) endocrine adipose, and d) the interplay among adipose, brain structure and function, and genes. This review will illustrate that adipose tissue is a quintessential, multifunctional tissue of the human body.
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| 69. |
- Gustafson, Deborah, 1966, et al.
(författare)
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New Perspectives on Alzheimer's Disease and Nutrition
- 2015
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Ingår i: Journal of Alzheimers Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 46:4, s. 1111-1127
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Tidskriftsartikel (refereegranskat)abstract
- Accumulating evidence shows nutritional factors influence the risk of developing Alzheimer's disease (AD) and its rate of clinical progression. Dietary and lifestyle guidelines to help adults reduce their risk have been developed. However, the clinical dementia picture remains complex, and further evidence is required to demonstrate that modifying nutritional status can protect the brain and prevent, delay, or reduce pathophysiological consequences of AD. Moreover, there is a pressing need for further research because of the global epidemic of overweight and obesity combined with longer life expectancy of the general population and generally observed decreases in body weight with aging and AD. A new research approach is needed, incorporating more sophisticated models to account for complex scenarios influencing the relationship between nutritional status and AD. Systematic research should identify and address evidence gaps. Integrating longitudinal epidemiological data with biomarkers of disease, including brain imaging technology, and randomized controlled interventions may provide greater insights into progressive and subtle neurological changes associated with dietary factors in individuals at risk for or living with AD. In addition, greater understanding of mechanisms involved in nutritional influences on AD risk and progression, such as oxidative stress and loss of neuronal membrane integrity, will better inform possible interventional strategies. There is consensus among the authors that nutritional deficits, and even states of excess, are associated with AD, but more work is needed to determine cause and effect. Appropriately designed diets or nutritional interventions may play a role, but additional research is needed on their clinical-cognitive effectiveness.
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| 70. |
- Gyllenhammar, Måns, et al.
(författare)
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The Association Between Temporal Atrophy and Episodic Memory Is Moderated by Education in a Multi-Center Memory Clinic Sample
- 2023
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 92:2, s. 605-614
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cognitive reserve (CR) is hypothesized to partially explain the discrepancy between Alzheimer’s disease related brain pathology and cognitive performance. Educational attainment is often used as a proxy for CR.Objective: To examine the association of years of education and the relationship between atrophy in the medial temporal lobe and episodic memory, in a cross-sectional ecological multi-center memory clinic cohort.Methods: Included patients (n = 702) had undergone memory clinic examination and were diagnosed with subjective cognitive impairment (n = 99), mild cognitive impairment (n = 471), or dementia (n = 132). Total years of education were used as a moderating variable and neuropathology was operationalized as visual ratings of medial temporal lobe atrophy (MTA) on magnetic resonance imaging and computer tomography images. Weighted least squares regression and multiple regression were used to analyze moderation and the effect of education separately by diagnostic group. A composite score of two episodic memory tests constituted the dependent variable.Results: After controlling for age and gender the interaction term between MTA and years of education was significant indicating moderation. In particular, the regression model showed that at low levels of MTA, high education individuals had better episodic memory performance. However, at higher MTA levels, high education individuals had the lowest episodic memory performance. Education had a significant positive effect on episodic memory in SCI and MCI, but not dementia.Conclusion: These results extend the findings of education moderating the effect of MTA on cognition to a naturalistic memory clinic setting. Implications of the findings for theories on CR are discussed.
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