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- 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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The Associations Between Serum Insulin-like Growth Factor-I, Brain White Matter Volumes, and Cognition in Mild Cognitive Impairment and Alzheimer's Disease
- 2024
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Ingår i: JOURNAL OF ALZHEIMERS DISEASE. - 1387-2877 .- 1875-8908. ; 99:2, s. 609-622
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Tidskriftsartikel (refereegranskat)abstract
- Background: Insulin-like growth factor-I (IGF-I) regulates myelin, but little is known whether IGF-I associates with white matter functions in subjective and objective mild cognitive impairment (SCI/MCI) or Alzheimer's disease (AD). Objective: To explore whether serum IGF-I is associated with magnetic resonance imaging - estimated brain white matter volumes or cognitive functions. Methods: In a prospective study of SCI/MCI (n = 106) and AD (n = 59), we evaluated the volumes of the total white matter, corpus callosum (CC), and white matter hyperintensities (WMHs) as well as Mini-Mental State Examination (MMSE), Trail Making Test A and B (TMT-A/B), and Stroop tests I-III at baseline, and after 2 years. Results: IGF-I was comparable in SCI/MCI and AD (113 versus 118 ng/mL, p = 0.44). In SCI/MCI patients, the correlations between higher baseline IGF-I and greater baseline and 2-year volumes of the total white matter and total CC lost statistical significance after adjustment for intracranial volume and other covariates. However, after adjustment for covariates, higher baseline IGF-I correlated with better baseline scores of MMSE and Stroop test II in SCI/MCI and with better baseline results of TMT-B and Stroop test I in AD. IGF-I did not correlate with WMH volumes or changes in any of the variables. Conclusions: Both in SCI/MCI and AD, higher IGF-I was associated with better attention/executive functions at baseline after adjustment for covariates. Furthermore, the baseline associations between IGF-I and neuropsychological test results in AD may argue against significant IGF-I resistance in the AD brain.
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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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