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Aggregation of phosphorylated tau (pTau) is a hallmark feature of Alzheimer’s disease (AD). Novel assays now allow pTau to be measured in plasma. Elevated plasma pTau predicts subsequent development of AD, cortical atrophy and AD-related pathologies in the brain. We aimed to determine whether elevated pTau is associated with cognitive functioning in older adults prior to the development of dementia.
Participants and Methods:
Independently living older adults (N = 48, mean age = 70.0 years; SD = 7.7; age range 55-88 years; 35.4% male) free of dementia or clinical stroke were recruited from the community and underwent blood draw and neuropsychological assessment. Plasma was assayed using the Quanterix Simoa® pTau-181 V2 Advantage Kit to quantify pTau-181 levels and APOE genotyping was conducted on the blood cell pellet fraction obtained from plasma separation. Global cognition was assessed using the Dementia Rating Scale-2 (DRS-2) and executive function was assessed using the Stroop, D-KEFS-2 Fluency, and Trails Making Test. Diagnosis of mild cognitive impairment (MCI) was determined based on overall neuropsychological performance. Participants were diagnosed as MCI if they scored >1 SD below norm-referenced values on 2 or more tests within a domain (language, executive, memory) or on 3 tests across domains.
Results:
Multiple linear regression analysis revealed a significant negative association between plasma pTau-181 levels and DRS-2 (B = -2.57, 95% CI (-3.68, -1.47), p <.001), Stroop Color-Word score (B = -2.64, 95% CI (-4.56, - 0.71), p = .009) and Fruits and Vegetables Fluency (B = -1.67, 95% CI (-2.84, -0.49), p = .007), adjusting for age, sex, education and APOE4 status. MCI diagnosis was determined for 43 participants, of which 8 (18.6%) met criteria. Logistic regression analysis revealed that pTau-181 levels are associated with increased odds of MCI diagnosis (OR = 2.18, 95% CI (1.01, 4.68), p = .046), after accounting for age, sex, education and APOE4 status.
Conclusions:
Elevated plasma pTau-181 is associated with worse cognition, particularly executive function, and predicts MCI diagnosis in older adults. Higher plasma pTau-181 was associated with increased odds of MCI diagnosis. Detection of pTau-181 in plasma allows a novel, non-invasive method to detect burden of one form of AD pathology. These findings lend support to the use of plasma pTau-181 as a valuable marker in detecting even early cognitive changes prior to the development of AD. Additional longitudinal studies are warranted to explore the prognostic value of plasma pTau-181 over time.
Blood pressure variability (BPV), independent of traditionally targeted average blood pressure levels, is an emerging vascular risk factor for stroke, cerebrovascular disease, and dementia, possibly through links with vascular-endothelial injury. Recent evidence suggests visit-to-visit (e.g., over months, years) BPV is associated with cerebrovascular disease severity, but less is known about relationships with short-term (e.g., < 24 hours) fluctuations in blood pressure. Additionally, it is unclear how BPV may be related to angiogenic growth factors that play a role in cerebral arterial health.
Participants and Methods:
We investigated relationships between short-term BPV, white matter hyperintensities on MRI, and levels of plasma vascular endothelial growth factor (VEGF) in a sample of community-dwelling older adults (n = 57, ages 55-88) without history of dementia or stroke. Blood pressure was collected continuously during a 5-minute resting period. BPV was calculated as variability independent of mean, a commonly used index of BPV uncorrelated with average blood pressure levels. Participants underwent T2-FLAIR MRI to determine severity of white matter lesion burden. Severity of lesions was classified as Fazekas scores (0-3). Participants also underwent venipuncture to determine levels of plasma VEGF. Ordinal logistic regression examined the association between BPV and Fazekas scores. Multiple linear regression explored relationships between BPV and VEGF. Models controlled for age, sex, and average blood pressure.
Results:
Elevated BPV was related to greater white matter lesion burden (i.e., Fazekas score) (systolic: OR = 1.17 [95% CI 1.01, 1.37]; p = .04; diastolic: OR = 2.47 [95% CI 1.09, 5.90]; p = .03) and increased levels of plasma VEGF (systolic: ß = .39 [95% CI .11, .67]; adjusted R2 = .16; p = .007; diastolic: ß = .48 [95% CI .18, .78]; adjusted R2 = .18; p = .003).
Conclusions:
Findings suggest short-term BPV may be related to cerebrovascular disease burden and angiogenic growth factors relevant to cerebral arterial health, independent of average blood pressure. Understanding the role of BPV in cerebrovascular disease and vascular-endothelial health may help elucidate the increased risk for stroke and dementia associated with elevated BPV.
This book presents a wide range of new research on many aspects of naval strategy in the early modern and modern periods. Among the themes covered are the problems of naval manpower, the nature of naval leadership and naval officers, intelligence, naval training and education, and strategic thinking and planning. The book is notable for giving extensive consideration to navies other than those ofBritain, its empire and the United States. It explores a number of fascinating subjects including how financial difficulties frustrated the attempts by Louis XIV's ministers to build a strong navy; how the absence of centralised power in the Dutch Republic had important consequences for Dutch naval power; how Hitler's relationship with his admirals severely affected German naval strategy during the Second World War; and many more besides. The book is a Festschrift in honour of John B. Hattendorf, for more than thirty years Ernest J. King Professor of Maritime History at the US Naval War College and an influential figure in naval affairs worldwide.
N.A.M. Rodger is Senior Research Fellow at All Souls College, Oxford.
J. Ross Dancy is Assistant Professor of Military History at Sam Houston State University.
Benjamin Darnell is a D.Phil. candidate at New College, Oxford.
Evan Wilson is Caird Senior Research Fellow at the National Maritime Museum, Greenwich.
Contributors: Tim Benbow, Peter John Brobst, Jaap R. Bruijn, Olivier Chaline, J. Ross Dancy, Benjamin Darnell, James Goldrick, Agustín Guimerá, Paul Kennedy, Keizo Kitagawa, Roger Knight, Andrew D. Lambert, George C. Peden, Carla Rahn Phillips, Werner Rahn, Paul M. Ramsey, Duncan Redford, N.A.M. Rodger, Jakob Seerup, Matthew S. Seligmann, Geoffrey Till, Evan Wilson
Loïc Wacquant shares with Norbert Elias and Pierre Bourdieu an interest in the mechanisms through which political, socioeconomic and cultural change leads to the transformation of human habitus in the modern world. There are few existing social analysts who have done more than Wacquant to place the neglect and deprivation of life in the urban periphery on the policy and research agendas of the social sciences. In drawing attention to the violence and de-pacification of the ‘hyper-ghetto’ in the US, and the ‘degraded ecology’ of the banlieues and marginal communities of Western Europe, the research agenda that is wrapped up in his analysis of advanced marginality is complementary to Elias's historical sociology of the processes that create divisions between the established and the outsiders in the modern world (Elias, 1982; Elias and Scotson, 1965). There seem to be real synergies between the two theoretical perspectives that this chapter explores.
There is a sense in which the Eliasian thesis on the civilising process has been waiting for Wacquant's emerging analysis of advanced marginality to boost its contemporary relevance: to sketch out a framework for understanding the circumstances that lead to de-civilising tendencies in present-day societies governed by neoliberal market principles. While Elias's developmental theory of the civilising process describes the consequences for social relationships and mentalities resulting from the pacification of society, he did not consider to any significant extent the contradictions of that process, and the theory has continued to appear less than convincing in accounting for the conflict, violence and disorderly features of Western society, both historically and today. Indeed it has often appeared to be a theory exclusively about the socially integrative aspects of modernity, about the sensibilities of the established to the neglect of documenting the experience and emotions of the outsiders.
It has been obvious for some time that what Eliasian process-sociology needed to preserve its currency was a coherent theory of the decivilising processes inherent in neoliberalism and global society. Eliasian sociology should be able to explain in a single theoretical structure the association between processes of pacification in contemporary Western societies with evidence of the deep-rooted disorder, violence and decay that disfigure marginal pockets of most large cities in the US and Europe today. Wacquant's analysis of advanced marginality, it is argued here, contributes to developing a rather neglected aspect of the civilising process.
The structure of plane steady shock waves in a gas with several internal energy modes which relax in parallel is investigated. Transport effects are neglected. Conditions for continuity and monotonicity of the velocity profile are discussed; when all modes have constant specific heats and relaxation times it is established that velocity must decrease monotonically. Internal mode energy contents may overshoot their local equilibrium values.
Numerical results for waves in a hypothetical gas with two relaxing modes are presented for purposes of illustration.
The article critically examines the assumption implicit in the research on social solidarity and popular attitudes that institutional solidarity equates with mutual care in society. Following a review of a selection of recent empirical research on social solidarity and popular attitudes to welfare it is concluded that the evidence points to general support for welfare based on self-interest and the principle of mutual insurance rather than social altruism. The analysis proceeds by arguing that social and economic changes which have resulted in social polarisation have weakened ‘functional democracy’ (the reciprocal dependency of one social group or class on another) leading to possible ‘decivilising tendencies’ and a decline in mutual empathy. The article argues that post-emotionalism may be the result of these processes: the breakdown in mutual knowledge across the class divide; the intellectualisation of feelings; interaction based on false ‘niceness’; the manipulation of emotions. The paper concludes by suggesting that post-emotional attitudes are the by-product of government social steering towards amoral familism in social policy through the provision of a ‘vocabulary of motives’ which are negative to state welfare.
