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T Sunderland

Publications and source records attributed to T Sunderland.

At least 109 records · Page 6Linked to original sources

Aging and mental health: primary care of the healthy older adult. A roundtable discussion: Part I.

Dementia, depression, alcoholism, and suicide are some of the most important mental health issues for the aging population. Among the factors that affect the physician's ability to evaluate and manage these disorders are drug-induced side effects, the ability and willingness of patients to communicate their feelings, the level of caregiver cooperation, and limitations imposed by federal regulations and reimbursement policies. In this first of three installments of a panel discussion, experts in geriatrics and geropsychiatry discuss healthy aging, age-related memory and sensory loss, changes in mentation postanesthesia, sexuality in the elderly, and side effects of common psychoactive medications.

Aged↗

Aging and mental health: diagnosis of dementia and depression.

In this second segment of a panel discussion on aging and mental health, panelists focus on the primary care evaluation and management of the patient with dementia, including differential diagnosis of depression. Other topics of discussion include the roles of psychiatric referral and psychotherapy in patient management, suicide prevention, and alcoholism in elderly patients.

Aged↗

The TRH stimulation test in Alzheimer's disease and major depression: relationship to clinical and CSF measures.

A blunted thyroid-stimulating hormone (TSH) response to exogenous thyrotropin-releasing hormone (TRH) has been reported to occur consistently in patients with major depression and less consistently in patients with Alzheimer's disease (AD). In this study we compared the TSH response to TRH in a large group (n = 40) of AD patients, elderly patients with major depression (n = 17), and age-matched controls (n = 14) to further characterize how it may relate to clinical variables, baseline thyroid function tests, and cerebrospinal fluid measures. Comparisons of TRH stimulation test response across all three groups revealed that patients with major depression had lower stimulated TSH levels (delta maxTSH) (p less than 0.02) and higher (though still within normal limits) mean thyroxine (T4) levels (p less than 0.05) than the AD patients or controls. AD patients with a blunted TSH response had a significantly higher mean free T4 (FT4) level (p less than 0.03) and tended to be more severely demented (p less than 0.01) than those with a nonblunted response.

Aged↗

A pilot placebo-controlled study of chronic m-CPP administration in Alzheimer's disease.

Meta-Chlorophenylpiperazine (m-CPP), a serotonin agonist and metabolite of the anti-depressant trazodone, was administered chronically to eight moderate to severely affected Alzheimer patients to determine whether it would produce improvement in behavioral symptoms complicating this illness. In doses up to 80 mg/day for 16 days, m-CPP was well tolerated and resulted in small but significant increases in anergy and depression-related symptoms compared with placebo. The effects of chronic m-CPP in this study contrast with the reported beneficial effects of the parent compound trazodone and selective 5-HT reuptake inhibitors in treating behavioral symptoms in Alzheimer patients.

Aged↗

Reduced cerebrospinal fluid dynorphin A1-8 in Alzheimer's disease.

Cerebrospinal fluid (CSF) measures of dynorphin A were compared in three groups. Alzheimer patients (n = 9), elderly depressives (n = 9), and age-matched normal controls (n = 9). The Alzheimer patients revealed a 40% decrease in CSF dynorphin compared with controls (36 +/- 15 versus 60 +/- 21 pg/ml, p less than 0.05). In contrast, other peptide measures [Neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), and galanin] remained unchanged across groups. This finding was further supported when an additional 20 Alzheimer patients with similar clinical backgrounds also showed reduced CSF dynorphin (37 +/- 13 pg/ml). CSF dynorphin did not correlate significantly with clinical variables or other CSF measures of monoamine metabolites [i.e., 3-methoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA)]. Given the previous report of increased kappa binding of Alzheimer brains at autopsy, the authors speculate about a possible up-regulation of opiate receptors in Alzheimer's disease and suggest ways to test this hypothesis in vivo.

Aged↗

CSF monoamine metabolites and somatostatin in Alzheimer's disease and major depression.

Decreased cerebrospinal fluid (CSF), somatostatinlike immunoreactivity (SLI) and alterations in the CSF monamine metabolites 3-methoxy-4-hydroxyphenylethylglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA) have been reported in patients with probable Alzheimer's disease (AD) and in patients with major depression. In this study, we found CSF SLI to be significantly lower in a large group of AD patients (n = 60) and in a group of age-matched patients with major depression (n = 18) as compared with normal controls (n = 12). Mean CSF, MHPG, 5-HIAA, and HVA levels were not significantly different among diagnostic groups. Within a group of "depressed" AD patients, CSF levels of 5-HIAA showed a significant positive correlation (p = 0.03) with CSF SLI; a similar relationship was found within the group of patients with major depression. Further exploration of the relationship between the somatostatin and serotonin systems may provide clues as to how neuropeptides interact with monoamine neurotransmitters and what role they have in depression.

Aged↗

A preliminary study of the effects of nighttime administration of the serotonin agonist, m-CPP, on sleep architecture and behavior in healthy volunteers.

The effects of m-chlorophenylpiperazine (m-CPP) (0.5 mg/kg) on sleep architecture and behavior were examined in six healthy volunteers following a single oral dose of the drug in a randomized, double-blind, placebo-controlled study. m-CPP reduced total sleep time (TST) and sleep efficiency in all subjects. Slow-wave sleep (SWS) and rapid-eye-movement (REM) sleep were decreased and stage 1 sleep was prolonged in a majority of subjects. Prominent behavioral and psychological effects were reported in five out of six subjects following m-CPP (but not following placebo) that interfered with sleep. The sleep disruption and behavioral activation following nighttime administration of m-CPP contrasts with the sedative properties of its parent compound, trazodone, suggesting that the hypnotic effect of trazodone is not related to the agonist profile of its metabolite, m-CPP.

Administration, Oral↗

The distribution of cerebral muscarinic acetylcholine receptors in vivo in patients with dementia. A controlled study with 123IQNB and single photon emission computed tomography.

A high-affinity muscarinic receptor antagonist, 123IQNB (3-quinuclidinyl-4-iodobenzilate labeled with iodine 123), was used with single photon emission computed tomography to image muscarinic acetylcholine receptors in 14 patients with dementia and in 11 healthy controls. High-resolution single photon emission computed tomographic scanning was performed 21 hours after the intravenous administration of approximately 5 mCi of IQNB. In normal subjects, the images of retained ligand showed a consistent regional pattern that correlated with postmortem studies of the relative distribution of muscarinic receptors in the normal human brain, having high radioactivity counts in the basal ganglia, occipital cortex, and insular cortex, low counts in the thalamus, and virtually no counts in the cerebellum. Eight of 12 patients with a clinical diagnosis of Alzheimer's disease had obvious focal cortical defects in either frontal or posterior temporal cortex. Both patients with a clinical diagnosis of Pick's disease had obvious frontal and anterior temporal defects. A region of interest statistical analysis of relative regional activity revealed a significant reduction bilaterally in the posterior temporal cortex of the patients with Alzheimer's disease compared with controls. This study demonstrates the practicability of acetylcholine receptor imaging with 123IQNB and single photon emission computed tomography. The data suggest that focal abnormalities in muscarinic binding in vivo may characterize some patients with Alzheimer's disease and Pick's disease, but further studies are needed to address questions about partial volume artifacts and receptor quantification.

Adult↗

Script generation as an indicator of knowledge representation in patients with Alzheimer's disease.

We examined script and lexical retrieval in patients with probable Dementia-Alzheimer's Type (DAT), Depressed patients, and normal controls. DAT patient breakdown in script production was structurally similar to their impaired lexical retrieval such that script events of low frequency and low centrality value were lost first. DAT patients also produced more events that fell outside the script boundary as well as more event-order errors. Four cases with DAT were identified on the basis of Z scores whose script production was at least 2 SDs greater than their lexical production or vice versa. This finding suggests that it may be possible to dissociate script and lexical knowledge and production processes. The findings lend partial support for a model of knowledge representation that includes parallel and partially redundant memory networks that are distinctly distributed in the brain.

Aged↗

Lack of seasonal variation in the births of patients with dementia of the Alzheimer type.

Seasonal variation in the birth rates of patients suffering from dementia of the Alzheimer type (DAT) was investigated in 150 patients, aged 42-88 years, and in 132 normal control subjects of comparable age and gender. No seasonal variation or cyclic trend could be demonstrated in the DAT patients compared with control subjects. The exclusion from the analysis of the patients with a positive family history did not change the results of the study, which further suggests that a seasonality in DAT birth rates is unlikely.

Adult↗

Multiple representations contribute to body knowledge processing. Evidence from a case of autotopagnosia.

Body schema disturbances were studied in a 62-yr-old woman with Alzheimer's disease. She was severely impaired in verbal and nonverbal tasks requiring her to localize body parts (on her own body, the examiner's body or a doll's body) even though she correctly named the same parts when pointed at by the examiner. Pointing responses were misdirected mainly to parts contiguous with the target area and, to a lesser extent, to functionally equivalent body parts. We also found that the patient was able to define body part names functionally but not spatially. In another series of tasks, and in contrast to the above results, performances were normal when small objects, attached to the patient's body, served as pointing targets. Furthermore, on subsequent testing she pointed correctly at the remembered position of these objects. The fact that the same point in 'body space' is localized correctly when it corresponds to an external object and erroneously when it corresponds to a body part contradicts the idea of the body schema as a unitary function. Learning the position of objects on the body surface requires access to some form of body-reference system on which this information can be mapped. We argue that such a system can be available in autotopagnosia and is independent from the visuospatial representations of the body structure that are postulated to be damaged or inaccessible in this syndrome. An integrated account of the present results and of those reported by other authors suggests that multiple levels of representation (e.g., sensorimotor, visuospatial, semantic) are involved in the organization of body knowledge.

Agnosia↗

Effects of daily oral m-chlorophenylpiperazine in elderly depressed patients. Initial experience with a serotonin agonist.

Six patients (mean age 62.5 +/- 7.6 years) with major depression were treated for 2 weeks with the serotonin agonist m-chlorophenylpiperazine (m-CPP), 80 mg/day in a double-blind, placebo-controlled, crossover-design pilot study. Two patients showed clinically significant improvement in depressive symptoms during active drug treatment, whereas two others showed modest effects. All patients tolerated the drug, with no major side effects and no changes in vital signs or in liver, renal, thyroid, or hematological function. Further studies are needed to determine the characteristics of the possible antidepressant effects of m-CPP; such work may yield greater understanding of the role of serotonin in affective and other psychiatric disorders.

Aged↗

TRH attenuates scopolamine-induced memory impairment in humans.

The brain tripeptide thyrotropin-releasing hormone (TRH) has been demonstrated to facilitate cholinergic neurotransmission. To test its interaction with the cholinergic system in humans, high-dose TRH (0.5 mg/kg) or placebo was administered intravenously (IV) to normal controls pretreated with scopolamine (0.5-0.75 mg IV), a centrally active muscarinic antagonist, which has been used to model aspects of the memory impairment of normal aging and of dementia. Compared to placebo, TRH markedly attenuated scopolamine-induced impairment of some measures of memory, most notably on a selective reminding task. This cognitive study is the first in humans to suggest a neuromodulatory effect of a peptide on the cholinergic system, and suggests a facilitatory role for TRH in human memory processes.

Adult↗

Neuroendocrine, physiologic, and behavioral responses following intravenous nicotine in nonsmoking healthy volunteers and in patients with Alzheimer's disease.

In separate studies, nonsmoking nicotine-naive subjects (11 young and middle-aged normal volunteers and 11 nonsmoking patients with Alzheimer's disease) received up to three doses of intravenous nicotine bitartrate (0.125, 0.25, and 0.5 micrograms/kg/min) and placebo for 60 min. Measurement of plasma ACTH, cortisol, and prolactin showed that nicotine produced in both groups a dose-dependent increase in cortisol, with ACTH in both groups and prolactin in the Alzheimer's group significantly elevated only by the 0.5 micrograms dose. Physiologic measures showed dose-dependent increases that were consistent with previous reports of nicotinic cholinergic stimulation. Behavioral effects included increases in anxiety and decreases in mood, especially following the 0.5 micrograms dose. Physical side effects were modest. The results indicate that nicotinic cholinergic stimulation can activate pituitary hormonal secretion in the human and suggest that nicotinic cholinergic stimulation may constitute an important part of cholinesterase inhibitor-induced endocrine stimulation and behavioral activation.

Adrenocorticotropic Hormone↗

Automatic memory processes in patients with dementia-Alzheimer's type (DAT).

We examined patients with Dementia-Alzheimer's Type, depression, and matched controls on tasks designed to compare automatic (monitoring frequency and modality) and effortful (free recall) processing of words and pictures. The results demonstrated that depressed patients performed poorly only when conditions required effortful processing, but DAT patients performed poorly under all conditions. There was almost no overlap in scores between DAT and elderly depressed patients on one of the measures of automatic processing suggesting that this measure may be clinically useful. The results suggest that automatic memory processes can be partially dissociated from effortful memory processes, but that both types of operations are impaired in DAT patients.

Aged↗

The dexamethasone suppression test in Alzheimer's disease and major depression: relationship to dementia severity, depression, and CSF monoamines.

Patients with Alzheimer's disease (AD) have been reported to have a rate of nonsuppression on the dexamethasone suppression test (DST) comparable to that of patients with major depression. With symptoms of depression being increasingly recognized in patients with AD, studying their DST response may provide clues to the etiology of the abnormal response in both diagnostic groups. A correlation between dementia severity and post-dexamethasone cortisol was found within the group of male, but not female AD patients. Within the group of elderly depressives, a correlation between post-dexamethasone cortisol and ratings of depression was found. Serum dexamethasone levels were not significantly lower in the nonsuppressors as compared with suppressors in either diagnostic group. Within the AD group, dexamethasone levels themselves correlated significantly with ratings of dementia severity and with the Wechsler Memory Scale score. Cerebrospinal fluid (CSF) 3-methoxy-4-hydroxyphenylglycol (MHPG) correlated positively with 4:00 pm post-dexamethasone cortisol level and with ratings of dementia severity in the AD patients. Findings are discussed in light of the known clinical and other biological similarities between AD and major depression, followed by a review of theories regarding the etiology of the hypothalamic-pituitary-adrenal abnormalities in these two illnesses.

Aged↗

Implicit learning in patients with Alzheimer's disease.

We examined implicit memory using priming and procedural learning tasks in patients with probable Dementia-Alzheimer's Type (DAT) to examine whether priming and procedural processes could be dissociated and whether task specificity was a factor in DAT patient performance. Priming was tested using a word recognition paradigm (perceptual priming) and by repeated administrations of a fragmented objects test (long term priming). Procedural learning was tested using repeated and random sequences on a choice serial reaction time task and by repeated administration of a puzzle map of the United States. DAT patients were compared to hospitalized depressed patients, patients suffering from Progressive Supranuclear Palsy (PSP), and normal controls. We found that DAT patients demonstrated marginal but significant implicit learning on both procedural learning and perceptual priming tasks. DAT patients performed relatively better on the procedural learning task than a perceptual priming task compared to PSP patients, suggesting that priming of meaningful stimuli is subserved by cortical structures whereas procedural motor responses to simple serial visual stimulus patterns can be maintained by subcortical systems. Furthermore, our findings suggest that priming and procedural processes can be dissociated and that task specificity is a factor in interpreting the results of implicit learning paradigms in DAT patients. The implications of these results for models of knowledge representation and memory processes as well as the way they can serve as models for testing nootropic drug effects are discussed.

Aged↗