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Trey Sunderland

Publications and source records attributed to Trey Sunderland.

28 records · Page 2Linked to original sources
PubMed2004

Context-specific memory and apolipoprotein E (ApoE) epsilon 4: cognitive evidence from the NIMH prospective study of risk for Alzheimer's disease.

The aim of the study was to determine whether the epsilon 4 allele of the apolipoprotein E (ApoE) gene was associated primarily with context-specific memory among individuals at genetic risk for developing Alzheimer's disease. The effect of ApoE status on comprehensive neuropsychological results was examined in 176 healthy adults during baseline cognitive testing in the NIMH Prospective Study of Biomarkers for Older Controls at Risk for Alzheimer's Disease (NIMH Prospective BIOCARD Study). The presence of the epsilon 4 allele was associated with significantly lower total scores on the Logical Memory II subtest of the Wechsler Memory Scale-Revised and percent of information retained after delay. Further analysis indicated the prose recall and retention effect was partially explained by a small subgroup of epsilon 4 homozygotes, suggesting a gradually progressive process that may be presaged with specific cognitive measures. The current results may represent an epsilon 4-associated breakdown between gist-related information and context-bound veridical recall. This relative disconnection may be understood in light of putative epsilon 4-related preclinical accumulation of Alzheimer pathology (tangles and plaques) in the entorhinal cortex (EC) and among frontal networks, as well as the possibility of less-efficient compensatory strategies.

Adult↗
PubMed2003

Higher in vivo muscarinic-2 receptor distribution volumes in aging subjects with an apolipoprotein E-epsilon4 allele.

The apolipoprotein E-epsilon4 allele confers an increased susceptibility to age-related memory problems and Alzheimer's disease. Abnormalities in the cholinergic system are also likely contributors to memory deficits associated with aging and AD. To determine the effect of the APOE-epsilon4 allele on the muscarinic component of the cholinergic system of aging subjects, 10 healthy subjects with APOE-epsilon4 alleles (APOE-epsilon4+) and 10 without (APOE-epsilon4-), ranging in age from 52 to 75 years, were tomographically scanned with the F-18-labeled muscarinic-2 (M2) selective agonist, 3-(3-(3-[(18)F]Flouropropyl)thio)-1,2,5-thiadiazol-4-yl)-1,2,5,6-tetrahydro-1-methylpyridine ([(18)F]FP-TZTP). The distribution volumes (V(T)) of [(18)F]FP-TZTP were determined by compartmental modeling of partial volume and free fraction corrected PET scans. Regional cerebral blood flow (rCBF) measurements with H(2) (15)O were also performed. Global Gray V(T) (840 +/- 155 ml plasma/ml tissue) was greater in APOE-epsilon4+ subjects than APOE-epsilon4- subjects (660 +/- 113 ml plasma/ml tissue, P = 0.01), and previously studied younger subjects. There were no significant differences between the groups with respect to rCBF, but within the APOE-epsilon4+ group there was a trend for subjects with the higher Global Gray V(T)s to have lower Global Gray CBFs (r = -0.65, P < 0.06). A lower concentration of acetylcholine in the synapse of APOE-epsilon4+ older individuals is a likely explanation for the greater [(18)F]FP-TZTP distribution volumes.

Aged↗
PubMed2003

Depression and Bipolar Support Alliance consensus statement on the unmet needs in diagnosis and treatment of mood disorders in late life.

OBJECTIVES: To review progress made during the past decade in late-life mood disorders and to identify areas of unmet need in health care delivery and research. PARTICIPANTS: The Consensus Development Panel consisted of experts in late-life mood disorders, geriatrics, primary care, mental health and aging policy research, and advocacy. EVIDENCE: (1) Literature reviews addressing risk factors, prevention, diagnosis, treatment, and delivery of services and (2) opinions and experiences of primary care and mental health care providers, policy analysts, and advocates. CONSENSUS PROCESS: The Consensus Development Panel listened to presentations and participated in discussions. Workgroups considered the evidence and prepared preliminary statements. Workgroup leaders presented drafts for discussion by the Consensus Development Panel. The final document was reviewed and edited to incorporate input from the entire Consensus Development Panel. CONCLUSIONS: Despite the availability of safe and efficacious treatments, mood disorders remain a significant health care issue for the elderly and are associated with disability, functional decline, diminished quality of life, mortality from comorbid medical conditions or suicide, demands on caregivers, and increased service utilization. Discriminatory coverage and reimbursement policies for mental health care are a challenge for the elderly, especially those with modest incomes, and for clinicians. Minorities are particularly underserved. Access to mental health care services for most elderly individuals is inadequate, and coordination of services is lacking. There is an immediate need for collaboration among patients, families, researchers, clinicians, governmental agencies, and third-party payers to improve diagnosis, treatment, and delivery of services for elderly persons with mood disorders.

Age Factors↗
PubMed2003

In vivo muscarinic 2 receptor imaging in cognitively normal young and older volunteers.

The precise effects of normal aging on the cholinergic system are unknown, as both in vitro and PET studies have shown conflicting results. In vivo determination of muscarinic receptor distribution and density has been hampered by both poor subtype selectivity and/or blood-brain barrier permeability of known ligands. Previous in vitro and in vivo work with the F-18 labeled muscarinic agonist, 3-(3- (3-[(18)F]Flouropropyl)thio)-1,2,5-thiadiazol-4-yl)-1,2,5,6-tetrahydro-1-methylpyridine ((18)FP-TZTP) suggested the use of (18)FP-TZTP to selectively quantify M2 receptors in humans. In this study, we used (18)FP-TZTP to infer M2 receptor avidity in the brains of 15 healthy younger subjects (mean age = 28.3 +/- 5.5 years) and 20 healthy older subjects (mean age = 62.1 +/- 7.7 years). Corrections for subject motion during the 120-min acquisition and partial voluming (PVC) were performed. A one-tissue compartment model was used to estimate the volumes of distribution (V(T)) of (18)FP-TZTP. Within both groups of subjects, volumes of distribution (K(1)/k(2)) in cortical, subcortical, and cerebellar areas were consistent with M2 receptor topography. Compared to younger subjects older subjects had significantly higher means and standard deviations for the volumes of distribution of (18)FP-TZTP throughout much of the cerebellum, cortex, and subcortex (Global Gray V(T) = 742 +/- 163 in older subjects and 645 +/- 74 in younger subjects, P < 0.03). Across all subjects (18)FP-TZTP, regional, and Global Gray distribution volumes were significantly correlated to age (Global Gray V(T,) r = 0.41, P < 0.01). A lower concentration of acetylcholine in the synapse of some older subjects is one possible explanation for the data.

Acetylcholine↗
PubMed2003

A collaborative study of the emergence and clinical features of the major depressive syndrome of Alzheimer's disease.

OBJECTIVE: This report provides a description of the prevalence and clinical features of the major depressive syndrome of Alzheimer's disease using data derived from structured diagnostic assessments of 243 patients with probable Alzheimer's disease and 151 nondemented elderly comparison subjects. METHOD: Subjects were characterized by a consortium of four Alzheimer's disease research centers and the Geriatric Psychiatry Branch of the National Institute of Mental Health. All sites administered the Clinical Assessment of Depression in Dementia, a structured, anchored diagnostic interview that was developed to reliably diagnose and characterize major depressive episodes in this population. RESULTS: Despite the use of a common, reliable methodology for the assessment and diagnosis of major depressive episodes, the prevalence of major depression in Alzheimer's disease ranged widely from 22.5% to 54.4% across the recruitment sites. The prevalence of major depressive episodes among Alzheimer's disease patients in the aggregate sample exceeded that for elderly comparison subjects and reached nearly 50% among the most severely demented patients. Alzheimer's disease patients with a current major depressive episode had earlier mean ages at onset, a higher mean Hamilton Depression Rating Scale score, and were more likely to be experiencing psychotic symptoms than those who had not developed a major depressive episode. Although the major depressive episodes of Alzheimer's disease patients and nondemented elderly comparison subjects included similar numbers of depressive symptoms, patients with Alzheimer's disease were more likely to report a diminished ability to concentrate or indecisiveness and less likely to experience sleep disturbances and feelings of worthlessness or excessive guilt during their major depressive episodes. None of the clinical features of major depression differed significantly in frequency among depressed Alzheimer's disease patients with mild, moderate, or severe dementia. Concurrent psychotic symptoms progressively increased with dementia severity. CONCLUSIONS: The high rate of major depressive episodes that occur after the onset of cognitive impairment among patients with Alzheimer's disease (the majority of whom had no premorbid history of major depression), common emergence in the early stages of dementia when symptoms of cognitive impairment are least likely to contribute to the syndromal diagnosis of major depression, and differences in the clinical presentations of the major depressive episodes of Alzheimer's disease patients and nondemented elderly comparison subjects, all support the validity of the major depressive syndrome of Alzheimer's disease. Our findings suggest that the major depressive syndrome of Alzheimer's disease may be among the most common mood disorders of older adults.

Age of Onset↗
PubMed2002

The apolipoprotein E gene, attention, and brain function.

The epsilon4 allele of the apolipoprotein E (ApoE) gene is associated with alterations in brain function and is a risk factor for Alzheimer's disease (AD). Changes in components of visuospatial attention with ApoE-epsilon4, aging, and AD are described. Healthy middle-aged adults without dementia who have the ApoE-epsilon4 gene show deficits in spatial attention and working memory that are qualitatively similar to those seen in clinically diagnosed AD patients. The findings support an association between ApoE polymorphism and specific components of visuospatial attention. Molecular mechanisms that may mediate the ApoE-attention link by modulating cholinergic neurotransmission to the posterior parietal cortex are discussed. Studies of attention and brain function in ApoE-epsilon4 carriers without dementia can advance knowledge of the genetics of visual attention, may enhance understanding of the preclinical phase of AD, and may lead to better methods for early AD detection.

Alzheimer Disease↗
PubMed2002

Views of potential subjects toward proposed regulations for clinical research with adults unable to consent.

OBJECTIVE: The authors' goal was to assess healthy individuals' attitudes toward five of the most prominent proposed safeguards regarding the consent process for research with adults unable to consent. METHOD: Telephone interviews were conducted with 246 individuals with a family history of Alzheimer's disease who had participated in clinical research. RESULTS: The majority of respondents said that they were willing to participate in research if they lost the ability to consent. Few completed a research advance directive. Many had discussed their preferences with their families, and the majority would allow their families to make research decisions for them. CONCLUSIONS: Enrolling individuals who are unable to consent in research that offers no potential for medical benefit is consistent with the preferences of at least some individuals. This suggests that such research should not be prohibited, provided there is sufficient evidence that it is consistent with the preferences of individual subjects. Requiring that such evidence be provided in a formal research advance directive may be unnecessarily restrictive. More research is needed to assess whether the findings in this group of subjects generalize to other groups.

Advance Directives↗
PubMed2002

Reminiscence group activities and discourse interaction in Alzheimer's disease.

Reminiscence is an enriching and complex experience having many purposes and functions when used with patients with Alzheimer's disease (AD). Discourse is a component of language that has been shown to decline in patients with AD (Mentis, Briggs-Whittaker, & Gramigna, 1995). This article represents one of the first studies to examine the effects of reminiscence group (RG) activities on discourse interactions in patients with AD. This article specifically addresses the AD population within a RG setting. Observations suggested that objective ratings of conversational discourse would be better (less impaired) in patients with AD when obtained in relatively unstructured environments (e.g., during RG activity) as compared to ratings obtained in conversational environments imposing more structure (e.g., a session in which language function was being evaluated). Comparisons made of conversational and narrative discourse skills observed during different testing environments in patients with AD revealed predicted outcomes. That is, discourse elicited in an environment that was less structured yielded qualitatively better discourse patterns, particularly related to selecting and maintaining a topic, requesting additional information about a topic, changing a topic during conversation, and turn-taking. Results are discussed in terms of their relevance to gerontological nurses managing patients with AD.

Adult↗
PubMedDate not supplied

Decreased beta-amyloid1-42 and increased tau levels in cerebrospinal fluid of patients with Alzheimer disease.

CONTEXT: Alzheimer disease (AD) is characterized by pathological results at autopsy of amyloid plaques and tau-associated neurofibrillary tangles, but the clinical diagnosis of AD is determined on the basis of medical history, cognitive symptoms, and exclusionary criteria. The search for antemortem biomarkers is intense and has focused on cerebrospinal fluid (CSF) beta-amyloid1-42 and tau proteins. OBJECTIVES: To compare CSF beta-amyloid and tau levels in a new population of AD patients and controls. To perform a meta-analysis of studies of CSF beta-amyloid and tau levels in AD patients and controls. DESIGN: Cross-sectional study of the comparison of baseline CSF beta-amyloid1-42 and tau levels in AD patients and controls. Meta-analysis involved 17 studies of CSF beta-amyloid and 34 studies of CSF tau. SETTING: Clinical research unit of the National Institute of Mental Health, Bethesda, Md. PATIENTS: The Geriatric Psychiatry Branch evaluated AD patients as inpatients at the National Institutes of Health Clinical Center between May 1985 and January 2001. A total of 203 patients participated in this study (131 with AD and 72 controls). None had other serious illnesses, and 31 of 131 AD cases had AD confirmed at autopsy. Meta-analysis provided an additional 3133 AD patients and 1481 controls. MAIN OUTCOME MEASURES: Levels of CSF beta-amyloid1-42 were measured by a sandwich enzyme-linked immunoabsorbent assay with a polyclonal capture antibody and a monoclonal detection antibody. Levels of CSF tau were measured with a standard commercial immunoassay. RESULTS: Levels of CSF beta-amyloid1-42 were significantly lower in the AD patients vs controls (mean [SD], 183 [121] pg/mL vs 491 [245] pg/mL; P<.001). Levels of CSF tau were significantly higher in AD patients (mean [SD], 587 [365] pg/mL vs 244 [156] pg/mL; P<.001). The cutpoints of 444 pg/mL for CSF beta-amyloid1-42 and 195 pg/mL for CSF tau gave a sensitivity and specificity of 92% and 89%, respectively, to distinguish AD patients from controls, which is comparable with rates with clinical diagnosis. Meta-analyses of studies comparing CSF beta-amyloid and tau levels in AD participants and controls confirmed an overall difference between levels in these 2 groups. CONCLUSIONS: Alzheimer disease is associated with a significant decrease in CSF beta-amyloid1-42 levels along with an increase in CSF tau levels. These findings suggest that the 2 measures are biological markers of AD pathophysiology. While these CSF measures may have a potential clinical utility as biomarkers of disease, the preliminary and retrospective nature of the findings, the absence of assay standardization, and the lack of comparison patient populations must be addressed in future studies testing the usefulness of these CSF measures for predictive, diagnostic, or treatment evaluation purposes.

Adult↗