A computational model of neurodegeneration in Alzheimer's disease.

Disruption of mental functions in Alzheimer's disease (AD) and related disorders is accompanied by selective degeneration of brain regions. These regions comprise large-scale ensembles of cells organized into systems for mental functioning, however the relationship between clinical symptoms of dementia, patterns of neurodegeneration, and functional systems is not clear. Here we present a model of the association between dementia symptoms and degenerative brain anatomy using F18-fluorodeoxyglucose PET and dimensionality reduction techniques in two cohorts of patients with AD. This reflected a simple information processing-based functional description of macroscale brain anatomy which we link to AD physiology, functional networks, and mental abilities. We further apply the model to normal aging and seven degenerative diseases of mental functions. We propose a global information processing model for mental functions that links neuroanatomy, cognitive neuroscience and clinical neurology.

Changes in Ventricular and Cortical Volumes following Shunt Placement in Patients with Idiopathic Normal Pressure Hydrocephalus.

BACKGROUND AND PURPOSE: While changes in ventricular and extraventricular CSF spaces have been studied following shunt placement in patients with idiopathic normal pressure hydrocephalus, regional changes in cortical volumes have not. These changes are important to better inform disease pathophysiology and evaluation for copathology. The purpose of this work is to investigate changes in ventricular and cortical volumes in patients with idiopathic normal pressure hydrocephalus following ventriculoperitoneal shunt placement. MATERIALS AND METHODS: This is a retrospective cohort study of patients with idiopathic normal pressure hydrocephalus who underwent 3D T1-weighted MR imaging before and after ventriculoperitoneal shunt placement. Images were analyzed using tensor-based morphometry with symmetric normalization to determine the percentage change in ventricular and regional cortical volumes. Ventricular volume changes were assessed using the Wilcoxon signed rank test, and cortical volume changes, using a linear mixed-effects model (P < .05). RESULTS: The study included 22 patients (5 women/17 men; mean age, 73 [SD, 6] years). Ventricular volume decreased after shunt placement with a mean change of -15.4% (P < .001). Measured cortical volume across all participants and cortical ROIs showed a mean percentage increase of 1.4% (P < .001). ROIs near the vertex showed the greatest percentage increase in volume after shunt placement, with smaller decreases in volume in the medial temporal lobes. CONCLUSIONS: Overall, cortical volumes mildly increased after shunt placement in patients with idiopathic normal pressure hydrocephalus with the greatest increases in regions near the vertex, indicating postshunt decompression of the cortex and sulci. Ventricular volumes showed an expected decrease after shunt placement.

Comparison of sporadic and familial behavioral variant frontotemporal dementia (FTD) in a North American cohort.

INTRODUCTION: Behavioral variant frontotemporal dementia (bvFTD) may present sporadically or due to an autosomal dominant mutation. Characterization of both forms will improve understanding of the generalizability of assessments and treatments. METHODS: A total of 135 sporadic (s-bvFTD; mean age 63.3 years; 34% female) and 99 familial (f-bvFTD; mean age 59.9; 48% female) bvFTD participants were identified. f-bvFTD cases included 43 with known or presumed chromosome 9 open reading frame 72 (C9orf72) gene expansions, 28 with known or presumed microtubule-associated protein tau (MAPT) mutations, 14 with known progranulin (GRN) mutations, and 14 with a strong family history of FTD but no identified mutation. RESULTS: Participants with f-bvFTD were younger and had earlier age at onset. s-bvFTD had higher total Neuropsychiatric Inventory Questionnaire (NPI-Q) scores due to more frequent endorsement of depression and irritability. DISCUSSION: f-bvFTD and s-bvFTD cases are clinically similar, suggesting the generalizability of novel biomarkers, therapies, and clinical tools developed in either form to the other.

Distinguishing clinical and radiological features of non-traumatic convexal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: The full spectrum of causes of convexal subarachnoid hemorrhage (cSAH) requires further investigation. Therefore, our objective was to describe the spectrum of clinical and imaging features of patients with non-traumatic cSAH. METHODS: A retrospective observational study of consecutive patients with non-traumatic cSAH was performed at a tertiary referral center. The underlying cause of cSAH was characterized and clinical and imaging features that predict a specific etiology were identified. The frequency of future cSAH or intracerebral hemorrhage (ICH) was determined. RESULTS: In all, 88 patients [median age 64 years (range 25-85)] with non-traumatic cSAH were identified. The most common causes were reversible cerebral vasoconstriction syndrome (RCVS) (26, 29.5%), cerebral amyloid angiopathy (CAA) (23, 26.1%), indeterminate (14, 15.9%) and endocarditis (9, 10.2%). CAA patients commonly presented at an older age than RCVS patients (75 years versus 51 years, P < 0.0001). Thirteen patients (14.7%) had recurrent cSAH, and 12 patients (13.6%) had a subsequent ICH. However, the risk was high amongst those with CAA compared to those caused by RCVS, with recurrent cSAH in 39.1% and subsequent lobar ICH in 43.5% of CAA cases. CONCLUSIONS: Our study demonstrates the clinical diversity of cSAH. Older age, sensorimotor dysfunction and stereotyped spells suggest CAA as the underlying cause. Younger age and thunderclap headache predict RCVS. Yet, various other causes also need to be considered in the differential diagnosis.

Clinical and imaging features of Othello's syndrome.

BACKGROUND AND PURPOSE: Our objective was to document the clinical and imaging features of Othello's syndrome (delusional jealousy). METHODS: The study design was a retrospective case series of 105 patients with Othello's syndrome that were identified using the Electronic Medical Record system of Mayo Clinic. RESULTS: The average age at onset of Othello's syndrome was 68 (25-94) years with 61.9% of patients being male. Othello's syndrome was most commonly associated with a neurological disorder (73/105) compared with psychiatric disorders (32/105). Of the patients with a neurological disorder, 76.7% had a neurodegenerative disorder. Seven of eight patients with a structural lesion associated with Othello's syndrome had right frontal lobe pathology. Voxel-based morphometry showed greater gray matter loss predominantly in the dorsolateral frontal lobes in the neurodegenerative patients with Othello's compared to matched patients with neurodegenerative disorders without Othello's syndrome. Treatment success was notable for patients with dopamine agonist induced Othello's syndrome in which all six patients had improvement in symptoms following decrease in medication. CONCLUSIONS: This study demonstrates that Othello's syndrome occurs most frequently with neurological disorders. This delusion appears to be associated with dysfunction of the frontal lobes, especially the right frontal lobe.

Mood and motor effects of thalamic deep brain stimulation surgery for essential tremor.

PURPOSE: The aim of this study was to evaluate the effects of unilateral and bilateral ventralis intermedius (Vim) deep brain stimulation (DBS) on mood and motor function. METHODS: Thirty-one consecutive medication refractory patients with essential tremor who underwent unilateral or bilateral Vim DBS at University of Florida and returned for at least 6 -month follow-up completed the Visual Analog Mood (VAMS), the Beck Depression Inventory (BDI), and the Tremor Rating Scale (TRS) before and after surgery. We excluded all patients who were implanted at other institutions. RESULTS: The tense subscale of the VAMS improved significantly in both the unilateral and bilateral DBS groups (P < 0.001). On the VAMS afraid subscale, only the bilateral group trended toward improvement (P = 0.075). There were no significant changes for either group for the happy, confused, sad, angry, energetic or tired VAMS scores. TRS subscale scores all improved after unilateral and bilateral Vim DBS surgery (P < 0.001). CONCLUSIONS: Feelings of tenseness, tremor severity and ADLs improved following unilateral or bilateral Vim DBS for ET.