Anosognosia of memory deficits in dementia:biomarkers, connectivity, and clinical aspects

This Ph.D. thesis titled, Anosognosia of memory deficits in dementia: biomarkers, connectivity, and clinical aspects, is an effort to shed light on a neuropsychiatric phenomenon that has both academic research, as well as clinical practice implications. Anosognosia or unawareness of memory deficits is the main topic of this Ph.D. thesis that explores the implications of this neuropsychiatric phenomenon with neuroimaging measures, specifically functional brain connectivity, as well as clinical neurology and biomarker analysis. First, the current research definitions associated with the Alzheimer’s disease (AD) continuum (i.e., the National Institute on Aging and Alzheimer's Association 2018 AT(N) research framework classification) are put into context, followed by an introduction of brain connectivity as a biomarker of AD progression and the neural correlates of anosognosia reported in the literature as obtained from different neuroimaging techniques. After introducing the biological and neuroimaging implications of anosognosia in the AD continuum, the neural correlates of anosognosia based on the AT(N) classification are reported using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. Finally, this thesis touches upon the clinical implications of anosognosia in end-of-life decision-making

Covariant description of parametrized nonrelativistic Hamiltonian systems

The various phase spaces involved in the dynamics of parametrized nonrelativistic Hamiltonian systems are displayed by using Crnkovic and Witten's covariant canonical formalism. It is also pointed out that in Dirac's canonical formalism there exists a freedom in the choice of the symplectic structure on the extended phase space and in the choice of the equations that define the constraint surface with the only restriction that these two choices combine in such a way that any pair (of these two choices) generates the same gauge transformation. The consequence of this freedom on the algebra of observables is also discussed.Comment: 15 pages, latex file. corrected typos, minor changes done to match published versio

Berry Phase of a Resonant State

We derive closed analytical expressions for the complex Berry phase of an open quantum system in a state which is a superposition of resonant states and evolves irreversibly due to the spontaneous decay of the metastable states. The codimension of an accidental degeneracy of resonances and the geometry of the energy hypersurfaces close to a crossing of resonances differ significantly from those of bound states. We discuss some of the consequences of these differences for the geometric phase factors, such as: Instead of a diabolical point singularity there is a continuous closed line of singularities formally equivalent to a continuous distribution of `magnetic' charge on a diabolical circle; different classes of topologically inequivalent non-trivial closed paths in parameter space, the topological invariant associated to the sum of the geometric phases, dilations of the wave function due to the imaginary part of the Berry phase and others.Comment: 28 pages Latex, three uuencoded postcript figure

Alveolar hemorrhage associated with cocaine consumption.

Cocaine is an illegal drug; its abuse and toxicity are a public health problem due to its high morbidity and mortality. Cocaine can affect the cardiovascular, central nervous and respiratory systems. The case of a 42-year-old male without history of chronic or degenerative diseases, but previous cocaine consumption is presented in this report. The patient is admitted to the Emergency Department given that the clinical presentation included hemoptysis and dyspnea with mild to minimal activity, which evolved to orthopnea. Advanced airway management was required and supportive care at the Intensive Care Unit was provided. Imaging studies showed evidence compatible with alveolar hemorrhage diagnosis. In search of an autoimmune etiology, an antibody-screening panel was requested, reporting negative results for autoimmune disorders. The patient management was based on corticosteroid therapy and plasmapheresis to counter the persistent hemoptysis and hemoglobin serum level decline. The management strategy was based on the clinical suspicion of vasculitis and a torpid clinical evolution. Pulmonary sepsis ensued, resulting in patient's death. The necropsy report describes the primary cause of death as diffuse alveolar hemorrhage secondary to diffuse alveolar injury. This case report presents the detailed clinical, imagining and histopathological findings of a patient with alveolar hemorrhage secondary to cocaine consumption, as well as a review of the literature

Functional connectivity differences in Alzheimer's disease and amnestic mild cognitive impairment associated with AT(N) classification and anosognosia

Alzheimer's continuum biological profiles (A+T-N-, A+T+N-, A+T-N+, and A+T+N+) were established in the 2018 National Institute on Aging and Alzheimer's Association research framework for Alzheimer's disease (AD). We aim to assess the relation between AT(N) biomarker profiles and brain functional connectivity (FC) and assess the neural correlates of anosognosia. We assessed local functional coupling and between-network connectivity through between-group intrinsic local correlation and independent component analyses. The neural correlates of anosognosia were assessed via voxel-wise linear regression analysis in prodromal AD. Statistical significance for the FC analysis was set at p ≤ 0.05 false discovery rate (FDR)-corrected for cluster size. One hundred and twenty-one and 73 participants were included in the FC and the anosognosia analysis, respectively. The FC in the default mode network is greater in prodromal AD than AD with dementia (i.e., local correlation: T = 8.26, p-FDR &lt; 0.001, k = 1179; independent component analysis: cerebellar network, T = 4.01, p-FDR = 0.0012, k = 493). The default mode network is persistently affected in the early stages of Alzheimer's biological continuum. The anterior cingulate cortex (T = 2.52, p-FDR = 0.043, k = 704) is associated with anosognosia in prodromal AD.</p

Short- and Long-Term Functional Connectivity Differences Associated with Alzheimer's Disease Progression

Introduction: Progression of amnestic mild cognitive impairment (aMCI) to Alzheimer’s disease (AD) is a clinical event with highly variable progression rates varying from 10–15% up to 30–34%. Functional connectivity (FC), the temporal similarity between spatially remote neurophysiological events, has previously been reported to differ between aMCI patients who progress to AD (pMCI) and those who do not (i.e., remain stable; sMCI). However, these reports had a short-term follow-up and do not provide insight into long-term AD progression. Methods: Seventy-nine participants with a baseline and 78 with a 12-month, 51 with a 24-month, and 22 with a +48-month follow-up resting-state fMRI with aMCI diagnosis from the Alzheimer’s Disease Neuroimaging Initiative database were included. FC was assessed using the CONN toolbox. Local correlation and group independent component analysis were utilized to compare regional functional coupling and between-network FC, respectively, between sMCI and pMCI groups. Two-sample t tests were used to test for statistically significant differences between groups, and paired t-tests were used to assess cognitive changes over time. Results: All participants (i.e., 66 sMCI and 19 pMCI) had a baseline and a year follow-up fMRI scan. Progression from aMCI to AD occurred in 19 patients (10 at 12 months, 5 at 24 months, and 4 at &#x3e;48 months), while 73 MCI patients remained cognitively stable (sMCI). The pMCI and sMCI cognitive profiles were different. More between-network FC than regional functional coupling differences were present between sMCI and pMCI patients. Activation in the salience network (SN) and the default mode network (DMN) was consistently different between sMCI and pMCI patients across time. Discussion: sMCI and pMCI patients have different cognitive and FC profiles. Only pMCI patients showed cognitive differences across time. The DMN and SN showed local correlation and between-network FC differences between the sMCI and pMCI patient groups at multiple moments in time

Gauge-Yukawa Unification in Asymptotically Non-free Theories

We study asymptotically non-free gauge theories and search for renormalization group invariant (i.e. technically natural) relations among the couplings which lead to successful gauge-Yukawa unification. To be definite, we consider a supersymmetric model based on $SU(4)\times SU(2)_{R}\times SU(2)_{L}$. It is found that among the couplings of the model, which can be expressed in this way by a single one in the lowest order approximation, are the tree gauge couplings and the Yukawa coupling of the third generation. The corrections to the lowest order results are computed, and we find that the predictions on the low energy parameters resulting from those relations are in agreement with the measurements at LEP and Tevatron for a certain range of supersymmetry breaking scale.Comment: 15 pages, MPI-Ph/94-46, HD-THEP-94-33, NTUA.12/94, KANAZAWA-94-1