| 1. |
- Horvath, Alexandra, et al.
(författare)
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Low Serum Insulin-like Growth Factor-I Is Associated with Decline in Hippocampal Volume in Stable Mild Cognitive Impairment but not in Alzheimer's Disease
- 2022
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Ingår i: Journal of Alzheimers Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 88:3, s. 1007-1016
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Tidskriftsartikel (refereegranskat)abstract
- Background: Serum insulin-like growth factor-I (IGF-I) has shown some association with hippocampal volume in healthy subjects, but this relation has not been investigated in stable mild cognitive impairment (sMCI) or Alzheimer's disease (AD). Objective: At a single memory clinic, we investigated whether serum IGF-I was associated with baseline magnetic resonance imaging (MRI)-estimated brain volumes and longitudinal alterations, defined as annualized changes, up to 6 years of followup. Methods: A prospective study of patients with sMCI (n = 110) and AD (n = 60). Brain regions included the hippocampus and amygdala as well as the temporal, parietal, frontal, and occipital lobes, respectively. Results: Serum IGF-I was statistically similar in sMCI and AD patients (112 versus 123 ng/mL, p = 0.31). In sMCI, serum IGF-I correlated positively with all baseline MRI variables except for the occipital lobe, and there was also a positive correlation between serum IGF-I and the annualized change in hippocampal volume ( rs = 0.32, p = 0.02). Furthermore, sMCI patients having serum IGF-I above the median had lower annual loss of hippocampal volume than those with IGF-I below the median (p = 0.02). In contrast, in AD patients, IGF-I did not associate with baseline levels or annualized changes in brain volumes. Conclusion: In sMCI patients, our results suggest that IGF-I exerted neuroprotective effects on the brain, thereby maintaining hippocampal volume. In AD, serum IGF-I did not associate with brain volumes, indicating that IGF-I could not induce neuroprotection in this disease. This supports the notion of IGF-I resistance in AD.
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| 2. |
- Horvath, Alexandra, et al.
(författare)
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Patients with Alzheimer's Disease Have Increased Levels of Insulin-like Growth Factor-I in Serum but not in Cerebrospinal Fluid
- 2020
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877. ; 75:1, s. 289-298
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Tidskriftsartikel (refereegranskat)abstract
- Background: Insulin-like growth factor-I (IGF-I) is important for amyloid-β (Aβ) metabolism, and also interacts with the brain vasculature. In previous IGF-I studies, it has not been evaluated whether Alzheimer's disease (AD) patients had vascular comorbidities. Objective and Methods: A cross-sectional study of 40 consecutive non-diabetic AD patients and 36 healthy controls. We measured IGF-I in serum and cerebrospinal fluid (CSF) and also serum insulin. Mixed forms of AD and vascular dementia were excluded. Results: After adjustment for covariates including age, serum IGF-I level was higher in the AD group than in the controls, whereas CSF IGF-I and serum insulin were unchanged. Binary logistic regression confirmed that high serum IGF-I was associated with increased prevalence of AD [adjusted Odds Ratio (OR):=:1.83, 95% confidence interval (CI): 1.005-3.32 per standard deviation (SD) increase in serum IGF-I]. This association was more robust after exclusion of patients receiving treatment with acetylcholinesterase inhibitors or N-methyl D-aspartate (NMDA) receptor antagonists (OR:=:2.23, 95 % CI: 1.10-4.48). In the total study population (n:=:76) as well in the AD group (n:=:40), serum IGF-I correlated negatively with CSF Aβ1-42, and CSF IGF-I correlated positively with CSF/serum albumin ratio, CSF total tau, and CSF phosphorylated tau. Conclusion: In AD patients without major brain vascular comorbidities, serum but not CSF levels of IGF-I were increased after correction for covariates. This association was strengthened by exclusion of patients receiving medical treatment. Overall, the results support the notion of IGF-I resistance in mild AD dementia. © 2020 - IOS Press and the authors. All rights reserved.
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| 3. |
- Quinlan, Patrick, et al.
(författare)
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Altered thyroid hormone profile in patients with Alzheimer's disease
- 2020
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Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530. ; 121
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Tidskriftsartikel (refereegranskat)abstract
- Background: Epidemiological studies have linked higher levels of thyroid hormones (THs) to increased risk of Alzheimer's disease (AD), whereas in advanced AD, THs have been unchanged or even decreased. In early AD dementia, little is known whether THs are related to AD neuropathology or brain morphology. Methods: This was a cross-sectional study of 36 euthyroid AD patients and 34 healthy controls recruited at a single memory clinic. Levels of THs were measured in serum and cerebrospinal fluid (CSF). In addition, we determined AD biomarkers (amyloid-beta(1-42), total tau and phosphorylated tau) in CSF and hippocampal and amygdalar volumes using magnetic resonance imaging.2 Results: Serum free thyroxine (FT4) levels were elevated, whereas serum free triiodothyronine (FT3)/FT4 and total T3 (TT3)/total T4 (TT4) ratios were decreased, in AD patients compared to controls. In addition, serum TT4 was marginally higher in AD (p = 0.05 vs. the controls). Other TH levels in serum as well as CSF concentrations of THs were similar in both groups, and there were no correlations between THs and CSF AD biomarkers. However, serum FT3 correlated positively with left amygdalar volume in AD patients and serum TT3 correlated positively with left and right hippocampal volume in controls. Conclusions: Thyroid hormones were moderately altered in mild AD dementia with increased serum FT4, and in addition, the reduced T3/T4 ratios may suggest decreased peripheral conversion of T4 to T3. Furthermore, serum T3 levels were related to brain structures involved in AD development.
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| 4. |
- Quinlan, Patrick, et al.
(författare)
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Higher thyroid function is associated with accelerated hippocampal volume loss in Alzheimer's disease
- 2022
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Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530. ; 139
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Tidskriftsartikel (refereegranskat)abstract
- Background: In epidemiological studies, higher thyroid hormone (TH) levels have been associated with lower brain volume and increased risk of Alzheimer's disease (AD) in elderly individuals. However, the relationships between serum THs and hippocampal atrophy rates have previously not been investigated. Methods: A prospective study of patients with AD (n = 55), stable mild cognitive impairment (sMCI; n = 84) and healthy controls (n = 29) recruited at a single memory clinic. We investigated whether serum THs were associated with magnetic resonance imaging (MRI)-estimated hippocampal volumes at baseline and with longitudinal alterations, defined as annualized percent changes. Results: Serum levels of free triiodothyronine (FT3) and FT3/free thyroxine (FT4) ratio were reduced in AD and sMCI patients compared with the controls (p < 0.05). Hierarchical linear regression analyses showed that higher serum FT3/FT4 ratio was associated with greater baseline hippocampal volume in all study groups. Only in AD patients, higher serum FT4 was associated with lower baseline volume of the left hippocampus. Finally, exclusively in the AD group, higher serum levels of FT3 and FT3/FT4 ratio, and lower serum TSH levels, were associated with greater annual hippocampal volume loss. Conclusions: In all study groups, FT3/FT4 ratio was related to baseline hippocampal volume. However, only in AD patients, higher levels of THs were associated with greater annual loss of hippocampal volume, suggesting that excessive TH levels exert a deleterious effect on the hippocampus in the presence of existing AD neuropathology. © 2022 The Authors
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| 5. |
- Quinlan, Patrick, et al.
(författare)
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Low serum concentration of free triiodothyronine (FT3) is associated with increased risk of Alzheimer's disease.
- 2019
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Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 1873-3360 .- 0306-4530. ; 99, s. 112-119
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Tidskriftsartikel (refereegranskat)abstract
- In epidemiological studies, thyroid hormones (THs) have been associated with the risk of dementia. However, little is known of the relation between THs and risk of Alzheimer's disease (AD) or vascular dementia (VaD) in a memory clinic population.In a mono-center study, serum concentrations of thyroid-stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) were assessed in 302 patients. All patients had subjective or objective mild cognitive impairment and none received treatment with THs. Cox proportional hazards regression analyses was used to determine whether THs at baseline were associated with the risk of conversion to all-cause dementia, AD or VaD.During the follow-up (mean 2.8 years), 82 (28%) of the patients progressed to dementia [AD, n = 55 (18%) and VaD, n = 17 (6%)]. Serum concentrations of TSH, FT4, and FT3 did not associate with all-cause dementia or VaD. Higher serum FT3 was associated with lower risk of conversion to AD [hazard ratio (HR) = 054; 95% confidence interval (CI): 0.32-0.92 per 1 pmol/L increase]. Furthermore, patients in the lowest serum FT3 quartile had a twofold increased risk of AD compared to those in the highest quartile (HR = 2.63; 95% CI: 1.06-6.47). These associations remained after adjustment for multiple covariates.In a memory clinic population, there was an inverse, linear association between serum FT3 and risk of AD whereas THs did not associate with all-cause dementia or VaD. Further studies are needed to determine the underlying mechanisms as well as the clinical significance of these findings.
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| 6. |
- Quinlan, Patrick, et al.
(författare)
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Low serum insulin-like growth factor-I (IGF-I) level is associated with increased risk of vascular dementia
- 2017
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Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530. ; 86, s. 169-175
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Tidskriftsartikel (refereegranskat)abstract
- Background Insulin-like growth factor-I (IGF-I) is important for the adult brain, but little is known of the role of IGF-I in Alzheimeŕs disease (AD) or vascular dementia (VaD). Methods A prospective study of 342 patients with subjective or objective mild cognitive impairment recruited at a single memory clinic. We determined whether serum IGF-I concentrations at baseline were associated with the risk of all-cause dementia, AD, or VaD. Patients developing mixed forms of AD and VaD were defined as suffering from VaD. The statistical analyses included Cox proportional hazards regression analysis. Results During the follow-up (mean 3.6 years), 95 (28%) of the patients developed all-cause dementia [AD, n = 37 (11%) and VaD, n = 42 (12%)]. Low as well as high serum IGF-I (quartile 1 or 4 vs. quartiles 2–3) did not associate with all-cause dementia [crude hazard ratio (HR) 1.30, 95% confidence interval (CI): 0.81–2.08 and crude HR 1.05, 95% CI: 0.63–1.75, respectively] or AD (crude HR 0.79, 95% CI: 0.35–1.79 and crude HR 0.94, 95% CI: 0.43–2.06, respectively]. In contrast, low serum IGF-I concentrations were associated with increased risk of VaD (quartile 1 vs. quartiles 2–3, crude HR 2.22, 95% CI: 1.13–4.36). The latter association remained significant also after adjustment for multiple covariates. Conclusions In a memory clinic population, low serum IGF-I was a risk marker for subsequent VaD whereas low IGF-I did not associate with the risk of AD. High serum IGF-I was not related to the risk of conversion to dementia. © 2017 Elsevier Ltd
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