The association between white matter hyperintensities (WMH) and amyloid accumulation over time in cognitively normal, amyloid-negative elderly people remains largely unexplored. In order to study ...whether baseline WMH were associated with longitudinal subthreshold amyloid accumulation, 159 cognitively normal participants from the Alzheimer’s Disease Neuroimaging Initiative who were amyloid-negative at baseline were examined. All the participants underwent a T1 and a Fluid-Attenuated Inversion Recovery MRI scan at baseline. Amyloid PET imaging was performed at baseline and follow-up visits in 2-year intervals for up to 8 years. Partial volume correction was applied for quantifying cortical Standardised Uptake Value Ratios (SUVR). The associations between global and regional WMH burden and amyloid accumulation were assessed using linear mixed models adjusted by demographic characteristics and baseline SUVR. Partial volume correction increased the measured annual rate of change (+2.4%) compared to that obtained from non-corrected data (+0.5%). There were no significant correlations between baseline WMHs and baseline subthreshold cortical amyloid uptake. In a longitudinal analysis, increased baseline cortical SUVR and increased baseline burden of global (p = 0.006), frontal (p = 0.006), and parietal WMH (p = 0.003) were associated with faster amyloid accumulation. WMH-related amyloid accumulation occurred in parietal, frontal, and, to a lesser extent, cingulate cortices. These results remained unchanged after a sensitivity analysis excluding participants with the highest cortical SUVRs. This is the first study to identify a specific spatial distribution of WMH which is associated with future amyloid accumulation in cognitively normal elderly subjects without PET-detectable amyloid pathology. These findings may have important implications in prevention trials for the early identification of amyloid accumulation.
•The relation between white matter lesions and amyloid accumulation is unclear.•Longitudinal Aβ-PET scans in Aβ-negative, normal elderly for up to 8 years.•A spatial pattern of WMH relates to amyloid accrual in Aβ-negative, normal elderly.•WMH patterns might help identify amyloid “accumulators”.
Background
Apolipoprotein E ε4 allele (APOEε4) is considered the major genetic risk factor of Alzheimer´s Disease (AD). Structural magnetic resonance imaging (sMRI) studies demonstrated that, ...compared to APOEε4 non‐carriers, APOEε4 carriers display structural changes in lateral and medial temporal lobe (MTL). However, the knowledge about the impact of this genotype on hippocampal subfields is still limited. The present sMRI study aimed to evaluate volumetric and cortical thickness differences between adults with mild cognitive impairment (MCI) APOEε4 non‐carriers compared with MCI‐APOEε4 carriers.
Method
Twelve MCI‐APOEε4 non‐carriers (mean age: 70.33 years, SD: 5.12) and ten MCI‐APOEε4 carriers (mean age: 72.70 years, SD: 6.38), diagnosed as MCI according Petersen criteria (Petersen, 2004; Albert et al., 2011), underwent neuropsychological assessment, cerebrospinal fluid, genetic and MRI examinations. MRI surface‐based morphometry analyses was conducted with the FreeSurfer software to evaluate volumetric and thickness differences in the hippocampal subfields and its surrounding MTL areas.
Result
Compared with MCI‐APOEε4 non‐carriers, the MCI‐APOEε4 carriers group showed a significant reduced volume in several areas of the left hemisphere. Specifically, in this hemisphere volumetric changes were found in the entorhinal cortex, the whole hippocampus and in its head, body and tail; the head of presubiculum, the head and body of subiculum, the CA1, CA3, CA4 subfields, the granulate cell of the molecular layer of dentate gyrus and the molecular layer of the hippocampus. This group also displayed a significant reduced volume in the right body of CA3 subfield.
Conclusion
These results suggest that, in MCI adults, the presence of the APOEε4 genotype may have an additional neuropathological impact on the structure of brain regions of the MTL with a critical functional role in episodic memory, the most affected neurocognitive system in Alzheimer’s disease (AD). Particularly, the left MTL would show higher vulnerability to neurodegenerative changes in the prodromal stage of AD.
Depression and cognitive impairment are intimately associated, especially in elderly people. However, the association between late-life depression (LLD) and mild cognitive impairment (MCI) is complex ...and currently unclear. In general, it can be said that LLD and cognitive impairment can be due to a common cause, such as a vascular disease, or simply co-exist in time but have different causes. To contribute to the understanding of the evolution and prognosis of these two diseases, this study’s primary intent was to explore the ability of artificial neural networks (ANNs) to identify an MCI subtype associated with depression as an entity by using the scores of an extensive neurological examination. The sample consisted of 96 patients classified into two groups: 42 MCI with depression and 54 MCI without depression. According to our results, ANNs can identify an MCI that is highly associated with depression distinguishable from the non-depressed MCI patients (accuracy = 86%, sensitivity = 82%, specificity = 89%). These results provide data in favor of a cognitive frontal profile of patients with LLD, distinct and distinguishable from other cognitive impairments. Therefore, it should be taken into account in the classification of MCI subtypes for future research, including depression as an essential variable in the classification of a patient with cognitive impairment.
Background
Our aim was to investigate the association of the NPS trajectories in time measured by MBI‐C for MCI patients with the CSF biomarkers and temporal lobe atrophy detected at baseline.
Method
...CSF biomarkers at baseline were obtained from 71 patients with MCI belonging to Compostela Aging Study (CompAS) (Spain). Positivity for A (β‐amyloid), T (p‐Tau), and N (t‐Tau) was defined by cut‐off levels. Structural MRI was employed to evaluate cortical thickness and volume. Mild behavioral impairment was assessed using the validated Spanish‐language MBI‐C (Mallo et al., 2018) at baseline, 24 months, and 60 months follow‐up. Spearman correlations were performed to evaluate the relationships between CSF biomarkers at baseline and MBI‐C scores for the three evaluations. Logistic regressions were used to test the predictive value of the MBI‐C scores at each evaluation on the biomarkers’ positivity at baseline, and linear regression analyses to test the relationships between cortical thickness and volume at baseline and the three MBI‐C scorings.
Results
Spearman correlations showed no significant relations between MBI‐C and β‐amyloid, pTau, tTau and tTau/β‐amyloid ratio at baseline. However, significant positive correlations appeared between MBI‐C at 24‐month follow‐up and pTau (rho = .371), tTau (rho = .282) and tTau/β‐amyloid ratio at baseline but not with β‐amyloid. MBI‐C scores at the 60‐month follow‐up only significantly correlated with tTau/β‐amyloid ratio (rho = ‐.418). MBI‐C at 24 months and at 60 months were respectively predicted by pTau and tTau (Table 1). Linear regression analyses showed that MBI‐C at 24 months was predicted by cortical thickness of entorhinal, fusiform, inferior temporal, inferior parietal, middle and supramarginal gyri. MBI‐C at 24 and 60 months were predicted by Volume of entorhinal, inferior temporal, precuneus and whole hippocampus (Table 2).
Conclusion
The markers of atrophy in structures of the medial temporal lobe and the lateral and parietal temporal lobe, and pTau+ or tTau+ in MCI patients at baseline were associated with worsening of neuropsychiatric symptoms at 24 and/or 60 months.
Abstract
Background
Mild cognitive impairment (MCI), clinically considered an intermediate state between the cognitive changes of normal aging and early dementia (Petersen, 2016), progress frequently ...to Alzheimer´s clinical syndrome. Alzheimer Disease (AD) biomarkers are used to evaluate the etiology and progression of MCI. In this study, we evaluated whether MCI participants with different profiles of CSF biomarkers (proposed by the National Institute on Aging and Alzheimer's Association ‐Jack et al., 2018‐) show differences in cortical thickness measures of the parahippocampal gyrus subregions.
Method
Seventy‐eight patients from the Compostela Aging Study diagnosed as MCI according to the Petersen criteria (Petersen, 2004; Albert et al., 2011) underwent neuropsychological assessment, CSF (β‐amyloid, p‐tau and t‐tau), and MRI cortical thickness measures of the parahippocampal gyrus. Subcortical segmentation of T1‐weighted MR images was conducted with FreeSurfer (6.0 version) using the “recon‐all” pipeline to obtain the mean thickness measures of the parahippocampal and the entorhinal cortex of each participant. Participants were classified into four groups according to CSF biomarkers: Group 1: Normal AD with MCI; Group 2: Alzheimer’s pathologic change with MCI; Group 3: Alzheimer’s disease with MCI (Prodromal AD); and Group 4: non‐Alzheimer’s pathologic change with MCI. General lineal models were performed to evaluate Group differences in the cortical thickness measures.
Results
The MCI Group 1 showed significantly higher cortical thickness than: a) Group 3 in right and left parahippocampal cortex, and b) Group 2 in right entorhinal cortex (Table 1 and Figure 1). No other significant differences were obtained.
Conclusions
The MCI CSF profile groups 3 (“prodromal AD”) and 2 (“Alzheimer´s pathologic change”) showed significant parahippocampal gyrus atrophy compared with MCI group 1 (“normal AD”). These results support MCI profiles proposed by Jack et al. (2018). Moreover, considering the degeneration of medial temporal lobe in AD, the aforementioned changes might have an AD diagnostic and prognostic value for both MCI groups.
Abstract
Background
Characterization of mild cognitive impairment (MCI) for clinical and research purposes involves identification of biological and neuropsychological markers in order to predict ...possible progression to dementia. The main aim of this work was to analyze the correlation of anthropometric measurements and plasmatic levels of leptin, testosterone and estrogens with cognitive, CSF and MRI regional atrophy markers in a sample of MCI participants.
Methods
Eighty‐one patients from the Compostela Aging Study diagnosed as MCI according to the Petersen criteria (Petersen, 2004; Albert et al., 2011) underwent neuropsychological assessment (CAMCOG‐R memory, CVLT short and long delayed free recall, subjective memory complains), CSF (Aβ
42
, t‐Tau and p‐Tau) and plasmatic analyses as well as an MRI study (parahippocampal and entorhinal cortex thickness measurements) (Table 1). Spearman’s correlation was used to evaluate the relationship between anthropometric measurements and blood test results with memory scores, CSF and MRI regional atrophy markers.
Results
Episodic memory scores correlated with CSF measurements (Aβ
42
, t‐Tau, p‐Tau) and parahippocampal and entorhinal cortical thickness (right and left) (Table 2). BMI, suprailiac, pectoral and subscapular skinfolds, circumference of waist, hip, arm and calf were negatively correlated with t‐Tau and p‐Tau levels. BMI, triccipital, thigh and pectoral skin folds as well as calf circumference were positively correlated with parahippocampal and entorhinal cortical thickness. Suprailiac, triccipital and thigh skin folds were positively correlated with episodic memory scores. Leptin plasma levels showed a negative correlation with CSF biomarkers (t‐Tau and p‐Tau) and a positive correlation with parahippocampal cortex thickness. Testosterone and estradiol levels showed a negative correlation with scores on memory tests and enthorhinal cortical thickness.
Conclusions
Our findings suggest that body composition is associated with episodic memory function, CSF biomarkers and cortical atrophy in patients with MCI. Leptin levels and sexual hormones may play a role in this association. These results point to a role of fat tissue and its regulating mechanisms in AD pathology and progression from MCI to dementia.
Background
Mild cognitive impairment (MCI), clinically considered an intermediate state between the cognitive changes of normal aging and early dementia (Petersen, 2016), progress frequently to ...Alzheimer´s clinical syndrome. Alzheimer Disease (AD) biomarkers are used to evaluate the etiology and progression of MCI. In this study, we evaluated whether MCI participants with different profiles of CSF biomarkers (proposed by the National Institute on Aging and Alzheimer's Association ‐Jack et al., 2018‐) show differences in cortical thickness measures of the parahippocampal gyrus subregions.
Method
Seventy‐eight patients from the Compostela Aging Study diagnosed as MCI according to the Petersen criteria (Petersen, 2004; Albert et al., 2011) underwent neuropsychological assessment, CSF (β‐amyloid, p‐tau and t‐tau), and MRI cortical thickness measures of the parahippocampal gyrus. Subcortical segmentation of T1‐weighted MR images was conducted with FreeSurfer (6.0 version) using the “recon‐all” pipeline to obtain the mean thickness measures of the parahippocampal and the entorhinal cortex of each participant. Participants were classified into four groups according to CSF biomarkers: Group 1: Normal AD with MCI; Group 2: Alzheimer’s pathologic change with MCI; Group 3: Alzheimer’s disease with MCI (Prodromal AD); and Group 4: non‐Alzheimer’s pathologic change with MCI. General lineal models were performed to evaluate Group differences in the cortical thickness measures.
Results
The MCI Group 1 showed significantly higher cortical thickness than: a) Group 3 in right and left parahippocampal cortex, and b) Group 2 in right entorhinal cortex (Table 1 and Figure 1). No other significant differences were obtained.
Conclusions
The MCI CSF profile groups 3 (“prodromal AD”) and 2 (“Alzheimer´s pathologic change”) showed significant parahippocampal gyrus atrophy compared with MCI group 1 (“normal AD”). These results support MCI profiles proposed by Jack et al. (2018). Moreover, considering the degeneration of medial temporal lobe in AD, the aforementioned changes might have an AD diagnostic and prognostic value for both MCI groups.
Background
Characterization of mild cognitive impairment (MCI) for clinical and research purposes involves identification of biological and neuropsychological markers in order to predict possible ...progression to dementia. The main aim of this work was to analyze the correlation of anthropometric measurements and plasmatic levels of leptin, testosterone and estrogens with cognitive, CSF and MRI regional atrophy markers in a sample of MCI participants.
Methods
Eighty‐one patients from the Compostela Aging Study diagnosed as MCI according to the Petersen criteria (Petersen, 2004; Albert et al., 2011) underwent neuropsychological assessment (CAMCOG‐R memory, CVLT short and long delayed free recall, subjective memory complains), CSF (Aβ42, t‐Tau and p‐Tau) and plasmatic analyses as well as an MRI study (parahippocampal and entorhinal cortex thickness measurements) (Table 1). Spearman’s correlation was used to evaluate the relationship between anthropometric measurements and blood test results with memory scores, CSF and MRI regional atrophy markers.
Results
Episodic memory scores correlated with CSF measurements (Aβ42, t‐Tau, p‐Tau) and parahippocampal and entorhinal cortical thickness (right and left) (Table 2). BMI, suprailiac, pectoral and subscapular skinfolds, circumference of waist, hip, arm and calf were negatively correlated with t‐Tau and p‐Tau levels. BMI, triccipital, thigh and pectoral skin folds as well as calf circumference were positively correlated with parahippocampal and entorhinal cortical thickness. Suprailiac, triccipital and thigh skin folds were positively correlated with episodic memory scores. Leptin plasma levels showed a negative correlation with CSF biomarkers (t‐Tau and p‐Tau) and a positive correlation with parahippocampal cortex thickness. Testosterone and estradiol levels showed a negative correlation with scores on memory tests and enthorhinal cortical thickness.
Conclusions
Our findings suggest that body composition is associated with episodic memory function, CSF biomarkers and cortical atrophy in patients with MCI. Leptin levels and sexual hormones may play a role in this association. These results point to a role of fat tissue and its regulating mechanisms in AD pathology and progression from MCI to dementia.
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