OBJECTIVE:To test whether higher global functional connectivity of the left frontal cortex (LFC) in Alzheimer disease (AD) is associated with more years of education (a proxy of cognitive reserve CR) ...and mitigates the association between AD-related fluorodeoxyglucose (FDG)-PET hypometabolism and episodic memory.
METHODS:Forty-four amyloid-PET–positive patients with amnestic mild cognitive impairment (MCI-Aβ+) and 24 amyloid-PET–negative healthy controls (HC) were included. Voxel-based linear regression analyses were used to test the association between years of education and FDG-PET in MCI-Aβ+, controlled for episodic memory performance. Global LFC (gLFC) connectivity was computed through seed-based resting-state fMRI correlations between the LFC (seed) and each voxel in the gray matter. In linear regression analyses, education as a predictor of gLFC connectivity and the interaction of gLFC connectivity × FDG-PET hypometabolism on episodic memory were tested.
RESULTS:FDG-PET metabolism in the precuneus was reduced in MCI-Aβ+ compared to HC (p = 0.028), with stronger reductions observed in MCI-Aβ+ with more years of education (p = 0.006). In MCI-Aβ+, higher gLFC connectivity was associated with more years of education (p = 0.021). At higher levels of gLFC connectivity, the association between precuneus FDG-PET hypometabolism and lower memory performance was attenuated (p = 0.027).
CONCLUSIONS:Higher gLFC connectivity is a functional substrate of CR that helps to maintain episodic memory relatively well in the face of emerging FDG-PET hypometabolism in early-stage AD.
This paper examines the processes through which the United Arab Emirates' (UAE) cities of Abu Dhabi and Dubai attract and integrate knowledge workers into their labor markets. It focuses on how the ...UAE has acquired the human capital to create post-oil economies, deploying its oil windfalls into massive urban development strategies in order to create global hubs for talent. More significantly, it analyzes how the UAE's strategies and frameworks for attracting global knowledge flows ultimately determine the degree to which expatriate knowledge embeds locally. Presentation of results from a large-scale human capital survey of firms in Dubai and Abu Dhabi, as well as key-informant interviews with senior human resource administrators at these firms, demonstrate these processes.
Several concepts, which in the aggregate get might be used to account for “resilience” against age- and disease-related changes, have been the subject of much research. These include brain reserve, ...cognitive reserve, and brain maintenance. However, different investigators have use these terms in different ways, and there has never been an attempt to arrive at consensus on the definition of these concepts. Furthermore, there has been confusion regarding the measurement of these constructs and the appropriate ways to apply them to research. Therefore the reserve, resilience, and protective factors professional interest area, established under the auspices of the Alzheimer's Association, established a whitepaper workgroup to develop consensus definitions for cognitive reserve, brain reserve, and brain maintenance. The workgroup also evaluated measures that have been used to implement these concepts in research settings and developed guidelines for research that explores or utilizes these concepts. The workgroup hopes that this whitepaper will form a reference point for researchers in this area and facilitate research by supplying a common language.
Alzheimer's disease (AD) is a progressive age-related neurodegenerative disease. At the time of clinical manifestation of dementia, significant irreversible brain damage is already present, rendering ...the diagnosis of AD at early stages of the disease an urgent prerequisite for therapeutic treatment to halt, or at least slow, disease progression. In this review, we discuss various neuroimaging measures that are proving to have potential value as biomarkers of AD pathology for the detection and prediction of AD before the onset of dementia. Recent studies that have identified AD-like structural and functional brain changes in elderly people who are cognitively within the normal range or who have mild cognitive impairment (MCI) are discussed. A dynamic sequence model of changes that occur in neuroimaging markers during the different disease stages is presented and the predictive value of multimodal neuroimaging for AD dementia is considered.
► Gulf succeeds in attracting global knowledge flows, but not in knowledge assimilation. ► Gulf institutional context constrains local learning. ► Foreign knowledge circulates within expatriate ...social spaces. ► Knowledge transfer inhibited by lack of foreign-local interactions. ► Exceptional success found in region’s financial sector.
This paper examines efforts by the United Arab Emirates and the other Arab Gulf States to use their oil wealth to “import” the human capital necessary to diversify their economies beyond oil. It explores how new forms of development capacity, necessary to create and sustain new industries in the Gulf, are acquired in the context of a global labor market. By studying the circulation and absorption of global human capital in the Gulf, this paper seeks to move beyond the focus on how institutions render flows of knowledge transferable or not. Instead, it emphasizes the ways in which institutions shape the ability of a place to assimilate and integrate foreign knowledge locally. This is accomplished by presenting results from surveys conducted with 300 foreign and local firms from throughout the Gulf region and key-informant interviews undertaken with 30 representatives of firms in Abu Dhabi and Dubai, United Arab Emirates. The results indicate that Gulf strategies to attract international investment, trade and migration have succeeded. These efforts, however, have not been accompanied by social integration mechanisms for the assimilation of external knowledge. Expatriate workers and foreign firms adapt their knowledge transactions for application to the region’s unique business and regulatory environments. Once in its localized form, this knowledge circulates within bounded, expatriate social spaces. These results, however, vary across key industries and locations. The key exception is found in the region’s financial sector, where local employment quotas have mandated high levels of learning via foreign–local interaction, and where locally embedded, personal relationships are the most valued asset a knowledge-worker can possess.
Primary pathologies including amyloid-β (Aβ) plaques and neurofibrillary tangles (NFT) develop many years before the onset of dementia symptoms in Alzheimer's disease (AD). Age-related small vessel ...disease (SVD) is common in elderly subjects and may contribute to the clinical syndrome of AD. Each type of pathology shows a specific spatio-temporal sequence of spreading in the brain. Here, we review neuropathological and neuroimaging findings (PET tracers of Aβ and NFT, MRI markers of SVD) to assess whether staging of these primary pathologies is useful to predict clinical symptoms in AD. On the basis of neuropathological data, early stages of Aβ plaque and NFT pathology distribution occur in preclinical AD, but advanced stages with spreading into further brain regions are associated with dementia symptoms. Amyloid PET presumably detects Aβ in advanced neuropathological Aβ stages, and increased global amyloid PET uptake is associated with clinical worsening in non-demented subjects. Tau PET may provide additional predictive value by detecting NFT in the allocortex. There is weak evidence that SVD is related to amyloid or NFT pathology. Global volume of MRI-assessed white matter hyperintensities (WMH) contribute in addition to biomarker levels of Aβ to predict cognitive decline. Regional differences of the effect of WMH on cognition have been demonstrated but are not yet established as a biomarker in AD. In conclusion, biomarkers for amyloid and tau pathology allow a distinction between early and advanced stages of AD, but a subgroup of pathologically identified preclinical AD cases is not identified by the currently available biomarkers.
Emerging evidence supports a role for innate immunity and microglia in Alzheimer's disease (AD) pathophysiology. However, no marker related to microglia has been included in the temporal evolution ...models of AD. TREM2 is a transmembrane protein involved in innate immunity and is selectively expressed by microglia and genetically linked to AD and other neurodegenerative disorders. Its ectodomain is released by proteolysis as a soluble variant (sTREM2) and can be detected in the cerebrospinal fluid (CSF). In patients with autosomal dominant AD, we tested how many years before the expected symptom onset did CSF sTREM2 increase in mutation carriers (MCs) compared to noncarriers (NCs). We also determined the temporal sequence of changes in CSF sTREM2 and markers for amyloid deposition and neurodegeneration as well as cognitive performance. We included 218 participants consisting of 127 MC and 91 NC siblings from the Dominantly Inherited Alzheimer Network. We observed that CSF sTREM2 increased in MCs compared to NCs 5 years before the expected symptom onset and this difference remained significant until 5 years after the expected symptom onset. Changes in CSF sTREM2 occurred after alterations were observed in markers for brain amyloidosis and neuronal injury. We propose that microglial activation occurs several years before the expected symptom onset, but after amyloidosis and neuronal injury have already occurred.
Objective
To establish a fully automated, robust imaging marker for cerebral small vessel disease (SVD) and related cognitive impairment that is easy to implement, reflects disease burden, and is ...strongly associated with processing speed, the predominantly affected cognitive domain in SVD.
Methods
We developed a novel magnetic resonance imaging marker based on diffusion tensor imaging, skeletonization of white matter tracts, and histogram analysis. The marker (peak width of skeletonized mean diffusivity PSMD) was assessed along with conventional SVD imaging markers. We first evaluated associations with processing speed in patients with genetically defined SVD (n = 113). Next, we validated our findings in independent samples of inherited SVD (n = 57), sporadic SVD (n = 444), and memory clinic patients with SVD (n = 105). The new marker was further applied to healthy controls (n = 241) and to patients with Alzheimer's disease (n = 153). We further conducted a longitudinal analysis and interscanner reproducibility study.
Results
PSMD was associated with processing speed in all study samples with SVD (p‐values between 2.8 × 10−3 and 1.8 × 10−10). PSMD explained most of the variance in processing speed (R2 ranging from 8.8% to 46%) and consistently outperformed conventional imaging markers (white matter hyperintensity volume, lacune volume, and brain volume) in multiple regression analyses. Increases in PSMD were linked to vascular but not to neurodegenerative disease. In longitudinal analysis, PSMD captured SVD progression better than other imaging markers.
Interpretation
PSMD is a new, fully automated, and robust imaging marker for SVD. PSMD can easily be applied to large samples and may be of great utility for both research studies and clinical use. Ann Neurol 2016;80:581–592.
Abstract Introduction Subjective cognitive decline (SCD) manifesting before clinical impairment could serve as a target population for early intervention trials in Alzheimer's disease (AD). A working ...group, the Subjective Cognitive Decline Initiative (SCD-I), published SCD research criteria in the context of preclinical AD. To successfully apply them, a number of issues regarding assessment and implementation of SCD needed to be addressed. Methods Members of the SCD-I met to identify and agree on topics relevant to SCD criteria operationalization in research settings. Initial ideas and recommendations were discussed with other SCD-I working group members and modified accordingly. Results Topics included SCD inclusion and exclusion criteria, together with the informant's role in defining SCD presence and the impact of demographic factors. Discussion Recommendations for the operationalization of SCD in differing research settings, with the aim of harmonization of SCD measurement across studies are proposed, to enhance comparability and generalizability across studies.
This research studies the labour and human capital dimensions of diversification and structural change in oil economies, with a focus on the case of the UAE and the Arab Gulf States. It examines how ...oil-driven development in the Gulf has resulted in entrenched patterns of employment and migration, which have forestalled efforts by these countries to transition into more sustainable, post-oil economies. Utilising a mixed methods approach based on secondary data analysis and a survey conducted with 300 firms, it studies how these distortions have evolved as the region has embarked on a number of major diversification efforts over the past four decades. Oil wealth has provided Gulf economies with the capital to create competitive new sources of economic growth, but the challenge remains sustainability: reproducing the labour force in non-oil industries locally.
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