Midlife occupational cognitive requirements protect cognitive function in old age by increasing cognitive reserve

INTRODUCTION: Several lifestyle factors promote protection against Alzheimer's disease (AD) throughout a person's lifespan. Although such protective effects have been described for occupational cognitive requirements (OCR) in midlife, it is currently unknown whether they are conveyed by brain maintenance (BM), brain reserve (BR), or cognitive reserve (CR) or a combination of them. METHODS: We systematically derived hypotheses for these resilience concepts and tested them in the population-based AgeCoDe cohort and memory clinic-based AD high-risk DELCODE study. The OCR score (OCRS) was measured using job activities based on the O*NET occupational classification system. Four sets of analyses were conducted: (1) the interaction of OCR and APOE-e4 with regard to cognitive decline (N = 2,369, AgeCoDe), (2) association with differentially shaped retrospective trajectories before the onset of dementia of the Alzheimer's type (DAT; N = 474, AgeCoDe), (3) cross-sectional interaction of the OCR and cerebrospinal fluid (CSF) AD biomarkers and brain structural measures regarding memory function (N = 873, DELCODE), and (4) cross-sectional and longitudinal association of OCR with CSF AD biomarkers and brain structural measures (N = 873, DELCODE). RESULTS: Regarding (1), higher OCRS was associated with a reduced association of APOE-e4 with cognitive decline (mean follow-up = 6.03 years), consistent with CR and BR. Regarding (2), high OCRS was associated with a later onset but subsequently stronger cognitive decline in individuals converting to DAT, consistent with CR. Regarding (3), higher OCRS was associated with a weaker association of the CSF Aß42/40 ratio and hippocampal volume with memory function, consistent with CR. Regarding (4), OCR was not associated with the levels or changes in CSF AD biomarkers (mean follow-up = 2.61 years). We found a cross-sectional, age-independent association of OCRS with some MRI markers, but no association with 1-year-change. OCR was not associated with the intracranial volume. These results are not completely consistent with those of BR or BM. DISCUSSION: Our results support the link between OCR and CR. Promoting and seeking complex and stimulating work conditions in midlife could therefore contribute to increased resistance to pathologies in old age and might complement prevention measures aimed at reducing pathology

Soluble TREM2 and inflammatory proteins in Alzheimer's disease cerebrospinal fluid

Contains fulltext : 220327.pdf (Publisher’s version ) (Closed access)The present study explores the associations of soluble TREM2, an important regulator of microglial activity linked to Alzheimer's disease (AD), with other known inflammatory proteins in cerebrospinal fluid (CSF). We studied 303 participants, including 89 controls, 135 mild cognitive impairment, and 79 AD dementia patients. Using established CSF biomarkers, subjects were classified according to the National Institute on Aging-Alzheimer's Association research framework, which groups markers into those of amyloid-beta deposition (A), tau pathology (T), and neurodegeneration (N). TNFR1, TNFR2, TGF-beta 1, TGF beta 2, IL-9, TNF-alpha, ICAM1, and VCAM1 showed significant concentration differences between the ATN groups, with higher concentrations in more advanced disease categories. sTREM2 was positively associated with the pro-inflammatory proteins TNF-a, TNFR1, TNFR2, ICAM1, VCAM1, and IP-10 and negatively with IL-21; also, positive associations with the anti-inflammatory proteins TGF beta 1, IL-10, and IL-9 were found. Pathway enrichment analysis highlighted the involvement of sTREM2 in key functional clusters including immunoglobulin and cytokine production and cellular response to lipopolysaccharides, cytokines, and steroid hormones. Our work provides further evidence in support of TREM2 as amarker of neuroinflammatory response in AD.12 p

Cerebral microhemorrhage at MRI in mild cognitive impairment and early Alzheimer disease: Association with tau and amyloid beta at PET imaging

In individuals with mild cognitive impairment and early Alzheimer disease, and in healthy individuals, MRI microhemorrhage count was associated with amyloid beta and tau load at PET. Background: Growing evidence indicates an association between cerebral microhemorrhages (MHs) and amyloid beta accumulation in Alzheimer disease (AD), but to the knowledge of the authors the association with tau burden is unknown. Purpose: To investigate the association between cerebral MH load and tau pathologic structure measured in healthy older individuals and individuals along the AD spectrum, stratified by using the A (amyloid beta)/T (tau)/N (neurodegeneration) biomarker classification system. Materials and methods: In this prospective cohort study, participants from the AD Neuroimaging Initiative were included (healthy control participants, participants with mild cognitive impairment, and participants with AD dementia; data from October 2005 to January 2019). T2*-weighted gradient-echo MRI was performed to quantify MH, fluorine 18 (F-18) flortaucipir (AV-1451) PET was performed to quantify tau, and F-18-florbetaben/F-18- florbetapir (AV45) PET was performed to quantify amyloid beta to study associations of MH with regional and global tau and amyloid beta load. Associations with cerebrospinal fluid (CSF) biomarkers (amyloid beta 1-42, total tau, phosphorylated tau 181) were also assessed. Analysis of covariance and Spearman rank correlation test for cross-sectional analysis and Wilcoxon signed rank test for longitudinal analyses were used, controlling for multiple comparisons (Bonferroni significance threshold, P < .008). Results: Evaluated were 343 participants (mean age, 75 years +/- 7; 186 women), including 205 participants who were A-TN (meanage, 73 years +/- 7; 115 women), 80 participants who were A+TN- (mean age, 76 years 6 7; 38 women), and 58 participants who were A+TN+ (mean age, 77 +/- 8; 34 women). MH count was associated with global (Spearman rho = 0.27; P =.004)and frontal (rho = 0.27; P =.005) amyloid beta load and global tau load (rho = 0.31; P =.001). In a longitudinal analysis, MH count increased significantly over approximately 5 years in the entire cohort (T-1, 81 [range, 0-6 participants]; T0, 214 [range, 0-58 participants]; P,.001), in A+TN+ (T-1, 20 [range, 0- 5 participants]; T0, 119 [range, 1-58 participants]; P,.001), A+TN-(T-1, 31 [range, 0-6 participants]; T0, 43 [ range, 0-8 participants]; P =.03), and A-TN- (T-1, 30 [range, 0-4 participants]; T0, 52 [range, 0-6 participants]; P =.007). A higher MH count was associated with higher future global (rho = 0.29; P =.008) and parietal (rho = 0.31; P =.005) amyloid beta and parietal tau load (rho = 0.31; P =.005). Conclusion: Cerebral microhemorrhage load is associated spatially with tau accumulation, both cross-sectionally and longitudinally

Metabolic correlates of dopaminergic loss in dementia with Lewy bodies

Contains fulltext : 220326.pdf (publisher's version ) (Open Access)Background: Striatal dopamine deficiency and metabolic changes are well-known phenomena in dementia with Lewy bodies and can be quantified in vivo by 123I-Ioflupane brain single-photon emission computed tomography of dopamine transporter and 18F-fluorodesoxyglucose PET. However, the linkage between both biomarkers is ill-understood. Objective: We used the hitherto largest study cohort of combined imaging from the European consortium to elucidate the role of both biomarkers in the pathophysiological course of dementia with Lewy bodies. Methods: We compared striatal dopamine deficiency and glucose metabolism of 84 dementia with Lewy body patients and comparable healthy controls. After normalization of data, we tested their correlation by region-of-interest–based and voxel-based methods, controlled for study center, age, sex, education, and current cognitive impairment. Metabolic connectivity was analyzed by inter-region coefficients stratified by dopamine deficiency and compared to healthy controls. Results: There was an inverse relationship between striatal dopamine availability and relative glucose hypermetabolism, pronounced in the basal ganglia and in limbic regions. With increasing dopamine deficiency, metabolic connectivity showed strong deteriorations in distinct brain regions implicated in disease symptoms, with greatest disruptions in the basal ganglia and limbic system, coincident with the pattern of relative hypermetabolism. Conclusions: Relative glucose hypermetabolism and disturbed metabolic connectivity of limbic and basal ganglia circuits are metabolic correlates of dopamine deficiency in dementia with Lewy bodies. Identification of specific metabolic network alterations in patients with early dopamine deficiency may serve as an additional supporting biomarker for timely diagnosis of dementia with Lewy bodies.11 p

Effect of aerobic exercise on cortical thickness in patients with schizophrenia: A dataset

This is a data article from the original publication "Effect of aerobic exercise combined with cognitive remediation on cortical thickness and prediction of social adaptation in patients with schizophrenia"[1]. Twenty-one patients with schizophrenia and 23 healthy controls underwent aerobic exercise. Another 21 patients with schizophrenia played table soccer instead. The 12-week exercise intervention was combined with computer-assisted cognitive remediation training from week 6 to week 12. Clinical assessments were conducted at baseline and after the 12-week intervention. Magnetic resonance imaging (MRI) scans were acquired at baseline then in weeks 6, 12, and 24. The thickness of the entorhinal, parahippocampal, and lateral and medial prefrontal cortices was assessed with FreeSurfer 6.0. Data are publicy available via https://osf.io/sfgxk/

Dual-phase beta-amyloid PET for assessment of neuronal injury and amyloidosis in corticobasal syndrome

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Value of FDG-PET as a supporting biomarker for dementia with Lewy bodies at stages of early dopaminergic loss

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Metabolic Correlates of Dopaminergic Loss in Dementia with Lewy Bodies

Background: Striatal dopamine deficiency and metabolic changes are well-known phenomena in dementia with Lewy bodies and can be quantified in vivo by 123 I-Ioflupane brain single-photon emission computed tomography of dopamine transporter and 18 F-fluorodesoxyglucose PET. However, the linkage between both biomarkers is ill-understood. Objective: We used the hitherto largest study cohort of combined imaging from the European consortium to elucidate the role of both biomarkers in the pathophysiological course of dementia with Lewy bodies