| 1. |
- Gil-Bea, Francisco J, et al.
(författare)
-
Insulin levels are decreased in the cerebrospinal fluid of women with prodomal Alzheimer's disease
- 2010
-
Ingår i: Journal of Alzheimer's Disease. - Amsterdam; Washington : IOS Press. - 1387-2877 .- 1875-8908. ; 22:2, s. 405-413
-
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.
|
|
| 2. |
- Imtiaz, Bushra, et al.
(författare)
-
Estradiol and Cognition in the Cardiovascular Risk Factors, Aging and Dementia (CAIDE) Cohort Study
- 2017
-
Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 56:2, s. 453-458
-
Tidskriftsartikel (refereegranskat)abstract
- Cardiovascular Risk factors, Aging and Dementia (CAIDE) is a Finnish population-based study. 731 cognitively normal women had self-reported hormone therapy (HT) data in 1998 as: no use, use <= 5 years, and >5 years. Information on type of HT was only available from 1995-1998 (Prescription Register). Cognition was assessed in 1998 and 2005-2008. Longterm (>5 years) HT use, especially use of estradiol alone among women having hysterectomy with bilateral oophorectomy, was associated with better episodic memory in 1998, but not in 2005-2008. Although a strong evidence for protective effect of estradiol on cognition was not observed in our study, improved global cognition among long-term users suggests that long-term postmenopausal HT may be beneficial for some cognitive domains.
|
|
| 3. |
- Leoni, Valerio, et al.
(författare)
-
Diagnostic Power of 24S-Hydroxycholesterol in Cerebrospinal Fluid: Candidate Marker of Brain Health
- 2013
-
Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 36:4, s. 739-747
-
Tidskriftsartikel (refereegranskat)abstract
- We evaluated the diagnostic potential of 24S-hydroxycholesterol (24OHC) in cerebrospinal fluid. At a memory clinic, we investigated subjects with subjective cognitive impairment (SCI, n = 33), mild cognitive impairment (MCI) patients (n = 27), MCI patients with later progression into Alzheimer dementia at follow up (n = 10), and patients with AD (n = 24). We also had a control group of healthy volunteers who did not later develop cognitive problems (n = 13). The fraction of the population with pathological levels of 24OHC was 8% in controls, 34% in SCI, 37% in MCI, 80% in MCI with progression, and 42% in AD. The corresponding fractions for T-tau, P-tau, and A beta(42) were lower in the case of SCI and MCI but higher in the case of controls and AD. In case of MCI with progression, the fraction of pathological levels of 24OHC and A beta(42) were 80% and 63% respectively. We also studied a population of old healthy subjects age 75-99 years (n = 25). The fraction of individuals in this population with pathological levels of 24OHC was 0% whereas the fraction of individuals with pathological level of at least one of the other three biomarkers was 40%. The diagnostic power of 24OHC in cerebrospinal fluid seems to be similar to or lower than that of the established biomarkers T-tau, P-tau, and A beta(42) in the diagnosis of established AD. Our data suggest that 24OHC may be more sensitive than the classical biomarkers in an early phase of the neurodegenerative process and a better marker for "brain health" in old age.
|
|
| 4. |
- Luikku, Antti J., et al.
(författare)
-
Predicting Development of Alzheimer's Disease in Patients with Shunted Idiopathic Normal Pressure Hydrocephalus
- 2019
-
Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 71:4, s. 1233-1243
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Idiopathic normal pressure hydrocephalus (iNPH) patients often develop Alzheimer's disease (AD) related brain pathology. Disease State Index (DSI) is a method to combine data from various sources for differential diagnosis and progression of neurodegenerative disorders.Objective: To apply DSI to predict clinical AD in shunted iNPH-patients in a defined population.Methods: 335 shunted iNPH-patients (median 74 years) were followed until death (n = 185) or 6/2015 (n = 150). DSI model (including symptom profile, onset age of NPH symptoms, atrophy of medial temporal lobe in CT/MRI, cortical brain biopsy finding, and APOE genotype) was applied. Performance of DSI model was evaluated with receiver operating characteristic (ROC) curve analysis.Results: A total of 70 (21%) patients developed clinical AD during median follow-up of 5.3 years. DSI-model predicted clinical AD with moderate effectiveness (AUC= 0.75). Significant factors were cortical biopsy (0.69), clinical symptoms (0.66), and medial temporal lobe atrophy (0.66).Conclusion: We found increased occurrence of clinical AD in previously shunted iNPH patients as compared with general population. DSI supported the prediction of AD. Cortical biopsy during shunt insertion seems indicated for earlier diagnosis of comorbid AD.
|
|
| 5. |
- Pekkala, Timo, et al.
(författare)
-
Association of Peripheral Insulin Resistance and Other Markers of Type 2 Diabetes Mellitus with Brain Amyloid Deposition in Healthy Individuals at Risk of Dementia
- 2020
-
Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 76:4, s. 1243-1248
-
Tidskriftsartikel (refereegranskat)abstract
- We explored the association of type 2 diabetes related blood markers with brain amyloid accumulation on PiB-PET scans in 41 participants from the FINGER PET sub-study. We built logistic regression models for brain amyloid status with12 plasma markers of glucose and lipid metabolism, controlled for diabetes and APOE ɛ4 carrier status. Lower levels of insulin, insulin resistance index (HOMA-IR), C-peptide, and plasminogen activator (PAI-1) were associated with amyloid positive status, although the results were not significant after adjusting for multiple testing. None of the models found evidence for associations between amyloid status and fasting glucose or HbA1c.
|
|
| 6. |
- Pentikainen, Heikki, et al.
(författare)
-
Cardiorespiratory Fitness and Cognition : Longitudinal Associations in the FINGER Study
- 2019
-
Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 68:3, s. 961-968
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Previous studies have found positive associations between cardiorespiratory fitness (CRF) and cognitive performance in older people but data are inconsistent and have methodological limitations. Objective: Our aimwas to study the longitudinal associations of CRF with executive functions, processing speed and memory as well as with the overall cognitive function in older people at risk for cognitive impairment. Methods: Participants (n = 421), mean age 69.0, were a sub-sample of The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER). To be eligible, individuals were required to be 60-77 years old with a CAIDE (Cardiovascular Risk Factors, Aging and Dementia) Dementia Risk Score of at least 6 points and cognition at mean level or slightly lower than expected for age. CRF was assessed as peak oxygen uptake (VO2peak, L/min) measured directly in a symptom-limited maximal exercise test on cycle ergometer at baseline and at 24 months. Cognitive performance was assessed using an extensive neuropsychological test battery (NTB) at baseline and at 24 months. NTB data were standardized to Z scores, and analyzed with the linear mixed model. Results: Over two years, VO2peak was associated with NTB total score (beta = 0.12, p = 0.01), executive functions (beta = 0.16, p = 0.01), and processing speed (beta = 0.25, p < 0.001), but not with memory (beta = 0.11, p = 0.12). Conclusion: Over two years follow-up, CRF was associated with executive functions and processing speed, and was related also to the overall cognitive function.
|
|
| 7. |
- Solomon, Alina, et al.
(författare)
-
Prevention of Alzheimer's Disease : Backward through the Lifespan
- 2013
-
Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 33, s. s465-S469
-
Forskningsöversikt (refereegranskat)abstract
- This is a brief summary of experiences from Finland related to Alzheimer's disease (AD) prevention research. The first signals that AD may have vascular modifiable risk factors came from studies on cardiovascular conditions and diabetes. Cardiovascular prevention projects such as North Karelia Project and WHO-MONICA in the 1970-1980s were focused on younger populations, which led to the idea of looking for risk factors as far back as middle age. Cardiovascular Risk Factors, Aging and Incidence of Dementia (CAIDE) is one of the few studies in the world focusing on late-life cognition with a large and representative population-based cohort, baseline examination at midlife, and follow-up time up to three decades. Since 1998, it has identified several modifiable risk factors for cognitive impairment/dementia, and produced the first risk score for estimating dementia risk based on midlife profiles. The CAIDE Dementia Risk Score has been used to select participants in the Finnish Geriatric Intervention Study to prevent cognitive impairment and disability (FINGER). FINGER is an ongoing multicenter RCT involving 1,200 participants aged 60-77 years, and testing the effects of a two-year multi-domain intervention targeting several risk factors simultaneously. It started in September 2009 and will be completed at the end of 2013. The FINGER study is at the forefront of international collaborative efforts to solve the clinical and public health problems of early identification of individuals at increased risk of late-life cognitive impairment, and of developing intervention strategies to prevent or delay the onset of cognitive impairment and dementia.
|
|
| 8. |
- Tolppanen, Anna-Maija, et al.
(författare)
-
Midlife Vascular Risk Factors and Alzheimer's Disease : Evidence from Epidemiological Studies
- 2012
-
Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 32:3, s. 531-540
-
Forskningsöversikt (refereegranskat)abstract
- The shared risk factor profile between cardiovascular diseases and Alzheimer's disease (AD), observations on vascular pathology in AD, and altered cerebral blood flow in AD brains have led to the suggestion that AD might be a vascular disorder with neurodegenerative consequences. Targeting vascular and metabolic risk factors could be an effective way to prevent AD. Higher body mass index, elevated blood pressure, serum cholesterol concentrations, and impaired glucose regulation have been associated with increased risk of AD. Interestingly, the associations between these factors measured at mid-life are stronger, or even opposite, than with the risk factors measured at late-life. This may reflect true differences in the association (i.e., mid-life risk factors being a better measure of vascular load during adulthood), reverse causality, or bias. The vascular risk factors can directly increase the susceptibility to AD, or the effect can be mediated via cardio- and cerebrovascular diseases.
|
|
| 9. |
- Wallin, Karin, et al.
(författare)
-
Midlife rheumatoid arthritis increases the risk of cognitive impairment two decades later : a population based study
- 2012
-
Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 31:3, s. 669-676
-
Tidskriftsartikel (refereegranskat)abstract
- Inflammation has been associated with Alzheimer's disease (AD) and dementia. The association between rheumatoid arthritis (RA) or arthritis and dementia/AD has been investigated in several case-control or hospital- and register-based studies with mixed results. This long-term population-based study investigates the association between presence of joint disorders (RA and other joint disorders) in midlife and cognitive status later in life. 1,449 participants were first evaluated in 1972, 1977, 1982, and 1987 and follow-up was performed after 21 years. A self-administered questionnaire including questions on joint disorders was used at both evaluations. Cognitive status (control, mild cognitive impairment, dementia/AD) was assessed at follow-up. The presence of any joint disorder in midlife was significantly associated with a worse cognitive status later in life: OR (95% CI) in an ordinal logistic regression analysis adjusted for age, gender, follow-up time, education, APOE epsilon 4, body mass index, smoking, drug treatment, and diabetes was 1.96 (1.17-3.28). For RA only, OR (95% CI) was 2.77 (1.26-6.10). The correlation remained significant for RA when AD was considered instead of dementia OR (95% CI) 2.49 (1.09-5.67). The presence of joint disorders, especially RA, at midlife seems to be associated with a worse cognitive status later in life. Given the chronic inflammatory component of RA, this study suggests that inflammatory mechanisms may have an important role in increasing the risk of cognitive impairment and dementia/AD.
|
|
| 10. |
- Zhang, Yanlei, et al.
(författare)
-
Cost-effectiveness of a health intervention program with risk reductions for getting demented : results of a Markov model in a Swedish/Finnish setting
- 2011
-
Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 26:4, s. 735-744
-
Tidskriftsartikel (refereegranskat)abstract
- Risk scores based on modifiable factors have recently been developed for dementia. This study aims to estimate the cost-effectiveness of a potential preventive intervention program meant to lower the score related to increased dementia risk. Analyses were based on a Markov model adapted to Swedish circumstances. Risk score categories and risk probabilities were derived from the Cardiovascular Risk Factors, Aging and Incidence of Dementia (CAIDE) study in Finland. Figures of costs, utilities, and mortality were obtained from literature or databases. One-way sensitivity analysis and probabilistic sensitivity analysis were carried out to investigate the robustness of the model and to identify which model inputs had most impact on the results. In the base case, the usual care had a cost of 621,000 SEK and utilities of 11.8438 quality-adjusted life year (QALYs). The intervention had a cost of 599, 026 SEK and utilities of 11.8950 QALYs. The cost was 21,974 SEK lower in the intervention with 0.0511 QALYs gained over a 20 years horizon, indicating absolute dominance. The support for cost-effectiveness was insensitive to changes in the value of QALY for demented, mortality, and risk of dementia. If the intervention program was assumed to run every year, the incremental cost-effectiveness ratio did not show absolute dominance but was still under the willingness-to-pay level. The probabilistic sensitivity analysis indicated cost effectiveness in 67% of the samplings given a willingness-to-pay level of 600,000 SEK/year. This is a promising outlook for future research on preventive interventions in dementia, emphasizing the need of conducting multi-domain randomized trials.
|
|
