NEUROPSYCHIATRIC SYMPTOMS OF DEMENTIA AND BIOMARKERS OF NEURODEGENERATION: CSF TAU AND MRI

Background: Behavioral and psychological symptoms of dementia (BPSD) are a distressful condition. We aimed to investigate the BPSD distribution in subjects with cognitive impairment, and the potential correlations between BPSD and neurodegeneration in terms of cerebrospinal fluid (CSF) tau and brain atrophy. Materials and Methods: One-hundred patients with mild cognitive impairment (MCI) or dementia (Alzheimer’s disease; Dementia with Lewy-body disease, DLB; frontotemporal dementia; vascular dementia) underwent a complete diagnostic workup, including 3T-MRI and/or CT and CSF. Cortical atrophy was assessed i) first with visual rating scales (medial temporal atrophy MTA, posterior atrophy PA and global cortical atrophy-frontal lobe GCA-F scales), ii) secondly with quantitative measures (such as cortical thickness CT and volume V). BPSD were rated using Neuropsychiatric Inventory (NPI), and BPSD clusters were defined according to the European Alzheimer Disease Consortium. Results: Delusions, hallucinations and psychosis cluster were differently distributed among the diagnostic groups (p<0.05, p<0.001, and p<0.05), with DLB patients showing higher scores for hallucinations (vs MCI, p<0.001, and AD, p<0.05) and psychosis cluster (vs MCI, p<0.05). In primary dementias, we found a negative correlation between NPI total score and tau levels (p=0.08), confirmed by beta regression (p<0.01), while a positive non-significant relationship was observed in MCI. Higher GCA-F scores were associated with delusions and apathy (p<0.05, on both hemispheres) and to hallucinations (left: p<0.01, right: p<0.05). GCA-F scores were positively correlated with psychosis cluster (right: p<0.05), and agitation/aggression (left: p<0.05). With regard to the quantitative measures od atrophy, significant correlations were observed for 4 main neuropsychiatric symptoms: delusions, hallucinations, agitation, and apathy. Delusions showed negative correlations with CT and V of frontal areas (dorsolateral and orbital, with a prevalent involvement on the right side) and of areas of the limbic system (anterior and posterior cingulate, isthmus and entorhinal cortex). As well, hallucinations showed an involvement of the frontal lobe (dorsolateral) and the limbic system (anterior and posterior cingulate, isthmus, fusiform gyrus and hippocampus). A decrease in CT and V of the opercular region (insula and temporal pole) and the limbic system (entorhinal, parahippocampal and fusiform cortex and amygdala) was instead correlated with agitation/aggression. Finally, apathy showed a negative correlation with regions of the frontal lobe (dorsolateral, orbital, opercular, precentral and paracentral) insula and the limbic system (anterior cingulate and isthmus). Conclusion: This study provides a real-world overview of the most clinically relevant BPSD occurring in patients attending a memory clinic due to dementing conditions. The gathered evidence suggests that, in a future perspective, CSF biomarkers and visual rating scales for cortical atrophy could be hopefully included in a multidimensional evaluation of demented patients, aimed to predict prognosis and occurrence of BPSD. Moreover, quantitative measures of atrophy suggest that the limbic system cover a paramount role in the their pathophysiology through the dysfunction of the mesolimbic circuitry.Background: Behavioral and psychological symptoms of dementia (BPSD) are a distressful condition. We aimed to investigate the BPSD distribution in subjects with cognitive impairment, and the potential correlations between BPSD and neurodegeneration in terms of cerebrospinal fluid (CSF) tau and brain atrophy. Materials and Methods: One-hundred patients with mild cognitive impairment (MCI) or dementia (Alzheimer’s disease; Dementia with Lewy-body disease, DLB; frontotemporal dementia; vascular dementia) underwent a complete diagnostic workup, including 3T-MRI and/or CT and CSF. Cortical atrophy was assessed i) first with visual rating scales (medial temporal atrophy MTA, posterior atrophy PA and global cortical atrophy-frontal lobe GCA-F scales), ii) secondly with quantitative measures (such as cortical thickness CT and volume V). BPSD were rated using Neuropsychiatric Inventory (NPI), and BPSD clusters were defined according to the European Alzheimer Disease Consortium. Results: Delusions, hallucinations and psychosis cluster were differently distributed among the diagnostic groups (p<0.05, p<0.001, and p<0.05), with DLB patients showing higher scores for hallucinations (vs MCI, p<0.001, and AD, p<0.05) and psychosis cluster (vs MCI, p<0.05). In primary dementias, we found a negative correlation between NPI total score and tau levels (p=0.08), confirmed by beta regression (p<0.01), while a positive non-significant relationship was observed in MCI. Higher GCA-F scores were associated with delusions and apathy (p<0.05, on both hemispheres) and to hallucinations (left: p<0.01, right: p<0.05). GCA-F scores were positively correlated with psychosis cluster (right: p<0.05), and agitation/aggression (left: p<0.05). With regard to the quantitative measures od atrophy, significant correlations were observed for 4 main neuropsychiatric symptoms: delusions, hallucinations, agitation, and apathy. Delusions showed negative correlations with CT and V of frontal areas (dorsolateral and orbital, with a prevalent involvement on the right side) and of areas of the limbic system (anterior and posterior cingulate, isthmus and entorhinal cortex). As well, hallucinations showed an involvement of the frontal lobe (dorsolateral) and the limbic system (anterior and posterior cingulate, isthmus, fusiform gyrus and hippocampus). A decrease in CT and V of the opercular region (insula and temporal pole) and the limbic system (entorhinal, parahippocampal and fusiform cortex and amygdala) was instead correlated with agitation/aggression. Finally, apathy showed a negative correlation with regions of the frontal lobe (dorsolateral, orbital, opercular, precentral and paracentral) insula and the limbic system (anterior cingulate and isthmus). Conclusion: This study provides a real-world overview of the most clinically relevant BPSD occurring in patients attending a memory clinic due to dementing conditions. The gathered evidence suggests that, in a future perspective, CSF biomarkers and visual rating scales for cortical atrophy could be hopefully included in a multidimensional evaluation of demented patients, aimed to predict prognosis and occurrence of BPSD. Moreover, quantitative measures of atrophy suggest that the limbic system cover a paramount role in the their pathophysiology through the dysfunction of the mesolimbic circuitry

Low-energy effective theory for a Randall-Sundrum scenario with a moving bulk brane

We derive the low-energy effective theory of gravity for a generalized Randall-Sundrum scenario, allowing for a third self-gravitating brane to live in the 5D bulk spacetime. At zero order the 5D spacetime is composed of two slices of anti-de Sitter spacetime, each with a different curvature scale, and the 5D Weyl tensor vanishes. Two boundary branes are at the fixed points of the orbifold whereas the third brane is free to move in the bulk. At first order, the third brane breaks the otherwise continuous evolution of the projection of the Weyl tensor normal to the branes. We derive a junction condition for the projected Weyl tensor across the bulk brane, and combining this constraint with the junction condition for the extrinsic curvature tensor, allows us to derive the first-order field equations on the middle brane. The effective theory is a generalized Brans-Dicke theory with two scalar fields. This is conformally equivalent to Einstein gravity and two scalar fields, minimally coupled to the geometry, but nonminimally coupled to matter on the three branes.Comment: 16 pages, 1 figure, typos correcte

Three-dimensional BF Theories and the Alexander-Conway Invariant of Knots

We study 3-dimensional BF theories and define observables related to knots and links. The quantum expectation values of these observables give the coefficients of the Alexander-Conway polynomial.Comment: 32 pages (figures available upon request); LaTe

Loop and Path Spaces and Four-Dimensional BF Theories: Connections, Holonomies and Observables

We study the differential geometry of principal G-bundles whose base space is the space of free paths (loops) on a manifold M. In particular we consider connections defined in terms of pairs (A,B), where A is a connection for a fixed principal bundle P(M,G) and B is a 2-form on M. The relevant curvatures, parallel transports and holonomies are computed and their expressions in local coordinates are exhibited. When the 2-form B is given by the curvature of A, then the so-called non-abelian Stokes formula follows. For a generic 2-form B, we distinguish the cases when the parallel transport depends on the whole path of paths and when it depends only on the spanned surface. In particular we discuss generalizations of the non-abelian Stokes formula. We study also the invariance properties of the (trace of the) holonomy under suitable transformation groups acting on the pairs (A,B). In this way we are able to define observables for both topological and non-topological quantum field theories of the BF type. In the non topological case, the surface terms may be relevant for the understanding of the quark-confinement problem. In the topological case the (perturbative) four-dimensional quantum BF-theory is expected to yield invariants of imbedded (or immersed) surfaces in a 4-manifold M.Comment: TeX, 39 page

Algebraic structures on graph cohomology

We define algebraic structures on graph cohomology and prove that they correspond to algebraic structures on the cohomology of the spaces of imbeddings of S^1 or R into R^n. As a corollary, we deduce the existence of an infinite number of nontrivial cohomology classes in Imb(S^1,R^n) when n is even and greater than 3. Finally, we give a new interpretation of the anomaly term for the Vassiliev invariants in R^3.Comment: Typos corrected, exposition improved. 14 pages, 2 figures. To appear in J. Knot Theory Ramification

Yeats’s Autobiographies and the Making of the Self

Both in his prose and poetry William Butler Yeats showed a life- long interest in the shaping of the self, achieved through a careful rearrangement of experience. Autobiographies is a collection of texts written at different times intentionally arranged by the author not according to the order of composition but to the chronological growth of the subject, from early childhood to the Nobel prize award. Until the period when autobiography started to be recognized as a specific genre with its own rules, this work was resorted to as a support for the study of the author’s production or as a key to discovering his life, disregarding the fact that autobiographical writing is not the narration of a life, but rather a narrative of the self as seen from the present moment of writing. Yeats’s Autobiographies is the narrative of how he struggled to shape his own personal identity as well as the identity of the nation. Life stories flourished in the Revival and post-Revival periods in Ireland, thus testifying to a widely shared belief in the correspondence of individual and national destiny. Along with collective drives, personal reasons also compelled him to look back and write his own autobiography. The author managed to provide a text in which everything, from syntactic to linguistic choices, from his treatment of time and places to his presentation of friends and rivals, combines to give a composite portrait of himself from early expectations to final achievement

Yeats’s Autobiographies and the Making of the Self

Both in his prose and poetry William Butler Yeats showed a life- long interest in the shaping of the self, achieved through a careful rearrangement of experience. Autobiographies is a collection of texts written at different times intentionally arranged by the author not according to the order of composition but to the chronological growth of the subject, from early childhood to the Nobel prize award. Until the period when autobiography started to be recognized as a specific genre with its own rules, this work was resorted to as a support for the study of the author’s production or as a key to discovering his life, disregarding the fact that autobiographical writing is not the narration of a life, but rather a narrative of the self as seen from the present moment of writing. Yeats’s Autobiographies is the narrative of how he struggled to shape his own personal identity as well as the identity of the nation. Life stories flourished in the Revival and post-Revival periods in Ireland, thus testifying to a widely shared belief in the correspondence of individual and national destiny. Along with collective drives, personal reasons also compelled him to look back and write his own autobiography. The author managed to provide a text in which everything, from syntactic to linguistic choices, from his treatment of time and places to his presentation of friends and rivals, combines to give a composite portrait of himself from early expectations to final achievement