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Biomedical subjects

S A Small

Publications and source records attributed to S A Small.

At least 19 recordsLinked to original sources

Age-related memory decline: current concepts and future directions.

The effect of age on memory and the brain has been the focus of many studies. Results have identified critical questions that need to be addressed to further our understanding of age-related memory decline: Is cognitive decline diffuse or selective? Where does memory decline localize to anatomically? Does decline represent an abnormal state? What are the causes of memory decline? What level of analysis is needed to investigate age-related cortical changes? These questions are reviewed herein, and attempts at early answers are discussed.

Aged↗

A novel phosphorylcholine-coated contact lens for extended wear use.

The preparation and characterisation of a new phosphorylcholine (PC)-coated silicone hydrogel contact lens for use in extended wear is described. The Michael-type addition of amines to acrylates forms the basis of the synthesis of a novel silicone-based macromer with hydrophilic functionality. It is demonstrated that this macromer can be combined with other silicone-based monomers, hydrophilic monomers and crosslinker to produce a contact lenses formulation. Examples of lenses with water contents of 33% and 46% are illustrated and their properties compared to other commercially available lenses. Materials with comparatively low modulus (<0.3 MPa) and adequate tear strength (>2-4MPa) with excellent elongation to break (>200%) can be obtained using this technology. In addition to the mechanical aspects. both the oxygen and solute permeabilities of the material can be controlled by the hydrophilic: hydrophobic monomer balance in the formulation. to obtain materials with attributes suitable for extended wear use. The PC coating is achieved by means of an in-mould coating (IMC) technique that produces a uniform and stable surface as determined by staining and XPS. The coating imparts both improved lens wettability (advancing contact angle of approximately 50 with virtually no hysteresis) and lower protein adsorption relative to the uncoated lens.

Adsorption↗

Circuit mechanisms underlying memory encoding and retrieval in the long axis of the hippocampal formation.

Circuits within the hippocampal formation are active during memory processing. Here we used functional magnetic resonance imaging (fMRI) to examine multiple sites across the long axis of the hippocampal formation while subjects performed different phases of an associative memory task, learning to associate faces with names. Viewing faces and hearing names in isolation resulted in separate hippocampal activation patterns. Pairing faces with names resulted a spatially redistributed activation pattern, rather than a simple summation of the activation patterns resulting from viewing faces and hearing names in isolation. Recalling names when cued with faces reactivated a pattern similar to that found during paired training. Finally, the activation patterns representing faces and names were found to be experience dependent, emerging with repeated exposure. Interpreted in the context of hippocampal anatomy and physiology, these findings reveal hippocampal circuit mechanisms that underlie memory encoding and retrieval.

Adult↗

Evaluating the function of hippocampal subregions with high-resolution MRI in Alzheimer's disease and aging.

Memory ability declines in older age groups. There is a growing list of physiological processes that target the hippocampal formation in an age-related fashion, and some might underlie the hippocampal component of memory decline. The hippocampal formation is comprised of separate subregions, and physiological processes differentially target these subregions. The ability to evaluate the functional integrity of individual subregions-performing subregional analysis-is a major clinical goal since it can aid in the diagnosis of memory decline, as well as in elucidating mechanisms of disease and testing potential interventions. Because of its superior spatial resolution, magnetic resonance imaging (MRI) is best suited to accomplish this goal. Despite limited success, most functional MRI (fMRI) protocols have difficulty in performing complete subregional analysis of the hippocampal formation. Here we address sources of difficulty by (1) generating T2* -weighted maps of the hippocampal formation with sub-millimeter resolution; and (2) by adapting an approach used by animal investigators to identify the hippocampal subregions using anatomical landmarks. The protocol is tested in patients with Alzheimer's disease and in healthy controls, in an effort to determine whether it can detect neuronal dysfunction. Results showed diminished signal in the hippocampal formation of patients with Alzheimer's disease (AD) compared to controls, and multivariate analysis showed that this difference was most prominent in the entorhinal cortex. The protocol can be used to perform subregional analysis of the hippocampal formation. Testing the protocol in other clinical populations is needed to demonstrate its efficacy in evaluating the neuronal integrity of all hippocampal subregions.

Aged↗

Endogenous estrogen levels and Alzheimer's disease among postmenopausal women.

BACKGROUND: Although several studies have suggested that hormone replacement therapy lowers the risk of AD among postmenopausal women, few studies have evaluated the relationship of endogenous estrogen levels and AD. The current study investigated whether serum estrone and estradiol levels were related to the presence of AD among postmenopausal women not currently taking hormone replacement therapy. METHODS: Using a case-control design, we examined an ethnically diverse sample of postmenopausal women who met National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for AD (n = 50) and nondemented controls (n = 93). All women were participants in a study of aging and dementia and were seen consecutively between August 1997 and October 1998. RESULTS: Patients with AD had lower estradiol (F[1,141] = 8.3, p = 0.005) levels than did normal controls. Patients also had lower estrone levels; however, this comparison did not quite meet significance criteria (F[1,141] = 3.6, p = 0.06). Compared to estradiol levels >20 pg/mL, women with AD were four to six times more likely to have levels <20 pg/mL after adjusting for age, years of education, presence of an APOE-epsilon4 allele, ethnicity, and body mass index. There were no significant differences in frequency of AD among women within different quartiles of estrone after adjusting for potential confounds. CONCLUSIONS: The results of this preliminary case-control study suggest that estradiol levels may decline significantly in women in whom AD develops.

Aged↗

Imaging physiologic dysfunction of individual hippocampal subregions in humans and genetically modified mice.

We have developed a variant of functional magnetic resonance imaging (fMRI) designed to be sensitive to static neuronal function. This method is based on resting instead of dynamic changes in oxygen-dependent signal and therefore allows for a spatial resolution that can detect signal from different hippocampal subregions in human subjects as well as in mice. We found that hippocampal signal was significantly diminished in elderly subjects with memory decline compared to age-matched controls, and different subjects showed dysfunction in different subregions. Among healthy elders, signal intensity from the subiculum was correlated selectively with memory performance. This method does not require an activation task; it can be used in anesthetized normal and in genetically modified and cognitively impaired mice. In mice the signal was found to be sufficiently sensitive to detect functional changes in the absence of underlying anatomical changes.

Aged↗

Selective decline in memory function among healthy elderly.

OBJECTIVE: To use longitudinally acquired data to establish whether aging is associated with memory decline. BACKGROUND: Memory loss is one of the most frequent complaints among the elderly. Nevertheless, age-related memory decline remains controversial in large part because it has been established with cross-sectional studies. METHODS: A total of 212 community-based healthy people were followed prospectively and evaluated annually with a neuropsychological battery testing memory and other cognitive domains. To control for the learning effect-the improvement in test performance associated with repeated exposure-longitudinal performance was compared between two age groups. RESULTS: The older age group displayed a relative decline in memory performance with time. In contrast to memory, a relative age-related decline was not observed in tests of language, visuospatial ability, and abstract reasoning. Furthermore, within the memory domain, age-related decline was restricted to a specific aspect of memory, manifesting only in a measure sensitive to the acquisition and early retrieval of new information, and not in a measure of memory retention. This profile of age-related cognitive decline anatomically localizes to the hippocampal formation. CONCLUSION: This study establishes age-related memory decline using longitudinal data, and shows that this decline does not occur diffusely across multiple cognitive domains. Both early AD as well as non-AD processes likely contribute to age-related memory decline, and continued follow-up may reveal distinguishing features between these two.

Aged↗

Differential regional dysfunction of the hippocampal formation among elderly with memory decline and Alzheimer's disease.

The hippocampal formation is composed of separate anatomical regions interconnected to form a circuit, and investigating abnormal hippocampal function is most revealing at the level of these regions. Until recently, regional analysis of the hippocampal formation could be performed only in animals or in human postmortem tissue. Here, we report a method using functional magnetic resonance imaging that evaluates the hippocampal regions in vivo, and we use this method to study elderly with normal memory, with isolated memory decline, and with probable Alzheimer's disease (AD). Although age-related memory decline occurs commonly, the cause of this decline remains unknown, with disagreement as to whether this decline represents one or more etiologies. Analysis revealed two distinct patterns of regional dysfunction among elderly with isolated memory decline--one pattern similar to that found in elders with AD, involving all hippocampal regions, and a second pattern with dysfunction restricted to only one hippocampal region, the subiculum. These results offer direct evidence of hippocampal dysfunction associated with memory decline in the elderly, and implicate both predementia AD and non-AD processes as possible underlying causes.

Aged↗

Plasma amyloid beta-peptide 1-42 and incipient Alzheimer's disease.

Mutations in the amyloid precursor protein and presenilin 1 and 2 genes result in elevated plasma levels of the amyloid beta-peptide species terminating at amino acid residue 42 (A beta1-42). In a longitudinal study of unrelated elderly individuals, those who subsequently developed Alzheimer's disease had higher plasma levels of A beta1-42 at entry than did those who remained free of dementia. The results indicate that elevated plasma levels of the released A beta peptide A beta1-42 may be detected several years before the onset of symptoms, supporting that extracellular A beta1-42 plays an important role in the pathogenesis of late-onset Alzheimer's disease.

Age of Onset↗

Effect of literacy on neuropsychological test performance in nondemented, education-matched elders.

The current investigation compared neuropsychological test performance among nondemented literate and illiterate elders. The sample included participants in an epidemiological study of normal aging and dementia in the Northern Manhattan community. All participants were diagnosed as nondemented by a neurologist, and did not have history of Parkinson's disease, stroke, or head injury. Literacy level was determined by self-report. MANOVAs revealed a significant overall effect for literacy status (literate vs. illiterate) on neuropsychological test performance when groups were matched on years of education. The overall effect of literacy status remained significant after restricting the analyses to elders with no formal education, and after controlling for the effects of language of test administration. Specifically, illiterates obtained lower scores on measures of naming, comprehension, verbal abstraction, orientation, and figure matching and recognition. However tests of verbal list delayed recall, nonverbal abstraction, and category fluency were unaffected by literacy status, suggesting that these measures can be used to accurately detect cognitive decline among illiterate elders in this sample. Differences in organization of visuospatial information, lack of previous exposure to stimuli, and difficulties with interpretation of the logical functions of language are possible factors that contribute to our findings.

Aged↗

Cognitive test performance among nondemented elderly African Americans and whites.

We examined the neuropsychological test performance of a randomly selected community sample of English-speaking non-Hispanic African American and white elders in northern Manhattan. All participants were diagnosed as nondemented by a neurologist, whose assessment was made independent of neuropsychological test scores. African American elders obtained significantly lower scores on measures of verbal and nonverbal learning and memory, abstract reasoning, language, and visuospatial skill than whites. After using a stratified random sampling technique to match groups on years of education, many of the discrepancies became nonsignificant; however, significant ethnic group differences on measures of figure memory, verbal abstraction, category fluency, and visuospatial skill remained. Discrepancies in test performance of education-matched African Americans and whites could not be accounted for by occupational attainment or history of medical conditions such as hypertension and diabetes. These findings emphasize the importance of using culturally appropriate norms when evaluating ethnically diverse elderly for dementia.

Aged↗

Multiple implants for first molar prosthodontics.

Problems that can occur when single implants are utilized to restore first molar teeth include the frequent loosening of screws, as well as screws and/or implant breakage. These may result from torquing and rotational movements of the prosthesis during masticatory and parafunctional mandibular movements. When sufficient bone and mesio-distal restorative space is present, the placement of two implants should be considered.

Dental Abutments↗

Sinus-lift graft: using the maxillary sinuses to support implants.

Often, the posterior region of the maxilla lacks the alveolar bone necessary to maintain an implant-supported prosthesis. The authors outline a procedure to augment the maxillary ridge using a composite alloplastic bone graft. The procedure also enables the practitioner to place implants at the time of the graft, reducing the surgical and healing time for the patient. Within six to 12 months of the bone graft, the patient can wear a fixed, implant-supported prosthesis. The authors report that patients who have been treated with this procedure have maintained stable implant prostheses for over five years.

Adult↗

Provisional and definitive prostheses following sinus lift and augmentation procedures.

Sinus lift and augmentation procedures with simultaneous insertion of cylindrical root form implants can be used to treat the atrophic posterior maxilla. The long-term use of a second stage provisional prosthesis is emphasized. The recommended metal-reinforced acrylic resin provisional restoration allows treatment and/or removal of a failing implant and progressive loading before fabrication of the definitive prosthesis. Modifications in prosthesis fabrication after sinus lift surgery and augmentation procedures are discussed.

Bicuspid↗

Nitric oxide and carbon monoxide produce activity-dependent long-term synaptic enhancement in hippocampus.

Nitric oxide (NO) and carbon monoxide (CO) may act as retrograde messages for long-term potentiation (LTP) in the hippocampus. Zinc protoporphyrin IX, an inhibitor of the enzyme that produces CO, blocked induction of LTP in the CA1 region of hippocampal slices. Application of either NO or CO to slices produced a rapid and long-lasting increase in the size of evoked synaptic potentials if, and only if, the application occurred at the same time as weak tetanic stimulation. This long-term enhancement was spatially restricted to synapses from active presynaptic fibers and appeared to involve mechanisms utilized by LTP, occluding the subsequent induction of LTP by strong tetanic stimulation. The enhancement by NO and CO was not blocked by an N-methyl-D-aspartate (NMDA) receptor blocker, suggesting that NO and CO act downstream from the NMDA receptor. Also, CO produced long-term enhancement when paired with low-frequency stimulation. These results are consistent with the hypothesis that NO and CO, either alone or in combination, serve as retrograde messages that produce activity-dependent presynaptic enhancement during LTP.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

First-stage fixed provisional restorations for implant prosthodontics.

Combination metal-and-acrylic-resin fixed provisional prostheses can be used in implant dentistry as an alternative to a removable provisional prosthesis. They may be fabricated in the laboratory and inserted on the day of fixture placement to ensure that the patients may return to their normal lifestyles with minimal discomfort or interruption in function and esthetics. These interim restorations may be used in free-standing as well as hybrid types of implant supported prostheses. The materials used and techniques of fabrication are described.

Dental Casting Technique↗

Augmenting the maxillary sinus for implants: report of 27 patients.

A method for restoring the posterior portion of the maxilla with a simultaneous composite alloplastic sinus lift graft and placement of press-fit implants is presented. Sinus grafting is needed because of minimal remaining alveolar bone. The composite graft material uses a combination of demineralized freeze-dried cortical bone and Interpore 200 hydroxyapatite. Since 1987, 45 sinus grafts with simultaneous placement of 111 root-form implants have been performed for 27 patients. None of the 76 restored implants have been lost. Complications were encountered in 2 patients (4 sinuses) who were heavy smokers. Antibiotics were administered, symptoms subsided, and the implants integrated.

Adult↗