ABSTRACT
BACKGROUND: Cognitive, global and functional instruments have been extensively investigated for correlations with neuropathological changes such as neurofibrillary tangles (NFTs), plaques, and synapse loss in the brain. OBJECTIVE: Our objective is to correlate the functional, global and cognitive decline assessed clinically with the neuropathological changes observed in a large prospectively characterized cohort of mild cognitive impairment (MCI) and Alzheimer's disease (AD). METHODS: We examined 150 subjects (16 MCI and 134 AD) that were prospectively assessed and longitudinally followed to autopsy. MCI subjects clinically met Petersen criteria for single or multi-domain amnestic MCI. AD subjects clinically met NINCDS-ADRDA criteria for probable or possible AD. All subjects received the Functional Assessment Staging (FAST), the Global Deterioration Scale (GDS), and the Mini Mental State Examination (MMSE) ante-mortem. Plaque and tangle counts were gathered for hippocampus, entorhinal cortex, frontal, temporal and parietal cortices. Braak staging was performed as well. RESULTS: The GDS, FAST and MMSE correlated with plaque counts in all regions. The GDS, FAST and MMSE correlated with tangle counts in in all regions. The three instruments also correlated with the Braak score. The MMSE and GDS correlate better than the FAST in most regions. CONCLUSIONS: Accumulation of neuropathology appears to correlate with functional, global, and cognitive decline as people progress from MCI through AD.
Subject(s)
Alzheimer Disease/pathology , Cognition Disorders/pathology , Aged, 80 and over , Alzheimer Disease/physiopathology , Alzheimer Disease/psychology , Cerebral Cortex/pathology , Cerebral Cortex/physiopathology , Cognition Disorders/physiopathology , Cognition Disorders/psychology , Cohort Studies , Disability Evaluation , Disease Progression , Entorhinal Cortex/pathology , Entorhinal Cortex/physiopathology , Female , Hippocampus/pathology , Hippocampus/physiopathology , Humans , Longitudinal Studies , Male , Neurofibrillary Tangles/pathology , Neuropsychological Tests/statistics & numerical data , Plaque, Amyloid/pathology , Predictive Value of Tests , Prognosis , Prospective Studies , Severity of Illness IndexABSTRACT
BACKGROUND AND OBJECTIVES: A preliminary study was conducted to examine a new surgical approach for the management of patients with open-angle glaucoma in which Schlemm's canal is opened to restore drainage in a nonpenetrating fashion. The authors compared the results of the surgical procedure including the new glaucoma drainage device with the results of standard trabeculectomy. PATIENTS AND METHODS: The authors performed a new type of surgical procedure on 58 consecutive patients with open-angle glaucoma. The procedure entails "deroofing" Schlemm's canal to facilitate the drainage of aqueous without penetrating the eye. This is done by exposing the canal after a partial-thickness sclerectomy and keratectomy along a 5-mm arc. After the canal was deroofed, a new type of collagen glaucoma drainage device was placed in the surgical site to maintain drainage postoperatively. Patient data, including intraocular pressure (IOP), complications, and the number of medications required to maintain adequate pressures, were analyzed for 1 year postoperatively. RESULTS: Within 1 to 2 months postoperatively, 80.9% of the patients achieved an IOP lower than 21 mm Hg. This improved to 88.9% at 3 to 6 months postoperatively and 87.5% at 6 to 12 months postoperatively. The only major complications were microperforations (8.6%) related to surgical technique and a few cases of high IOP that required repeat operations (10.3%). CONCLUSIONS: The nonpenetrating technique for deroofing the canal effectively allows the drainage of aqueous to acceptable levels (in the range of 15 to 17 mm Hg) without the complications associated with penetrating trabeculectomy. Complications are rare, and the collagen drainage device appears to be effective for allowing the drainage site to remain patent after its dissolution.
Subject(s)
Collagen , Drainage/instrumentation , Glaucoma, Open-Angle/surgery , Prosthesis Implantation , Sclerostomy/methods , Adult , Aged , Aqueous Humor/metabolism , Female , Glaucoma, Open-Angle/physiopathology , Humans , Intraocular Pressure/physiology , Male , Middle Aged , Postoperative Complications , Surgical Flaps , Trabeculectomy , Treatment OutcomeABSTRACT
Recently, an acute phase (AP) protein response has been reported in major depression. In order to examine whether an AP response occurs in other psychiatric disorders, such as schizophrenia and mania, the authors measured plasma AP reactants, such as haptoglobin (Hp), immunoglobulin G (IgG), IgM, fibrinogen (Fb), complement component 3 (C3C), C4, alpha 1-antitrypsin (alpha 1 AT), alpha 1-acid-glycoprotein (alpha 1S) and hemopexin (Hpx), in 27 schizophrenic, 23 manic, 29 major depressed and 21 normal subjects. Schizophrenic patients had significantly higher plasma Hp, Fb, C3C, C4, alpha 1S and Hpx than normal controls. Manic subjects showed significantly higher plasma Hp, Fb, alpha 1S and Hpx than normal volunteers. Depressed subjects had significantly higher plasma Hp, Fb, C3C, C4 and alpha 1S than normal controls. Overall, the above disorders in AP reactants were more pronounced in schizophrenic than in depressed subjects. No significant differences in the above AP reactants could be found between normal volunteers, and schizophrenic, manic or depressed patients who underwent chronic treatment with psychotropic drugs. Plasma Hp, Fb, C3C, C4, alpha 1S, and Hpx were significantly higher in schizophrenic, manic and depressed patients who were non-medicated than in those who were treated with antidepressants, antipsychotics or lithium. The results suggest that not only major depression but also schizophrenia and mania are accompanied by an AP response, and that the latter may be suppressed by (sub)chronic treatment with psychotropic drugs.
