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This study assessed unmet service needs of rural older adults with Alzheimer's disease (AD) and identified factors that were related to these needs. Data were collected from 109 informal caregivers of AD patients. Over half of the patients experienced unmet service needs in 1 or more areas of activities of daily functioning. Informal caregiver burden and patient's gender and functional status were significantly related to patients' unmet service needs. Patients' use of formal services was marginally related to their unmet service needs. To better address patients' service needs, a comprehensive needs assessment should be conducted with both patients and their caregivers.

We determined whether pentobarbital anesthetic is required to culture postmortem adult rat neurons. Pentobarbital treatment resulted in two-fold increases in neuron survival in culture after 2 and 4 h postmortem compared to non-anesthetic controls, but was not as effective as simple postmortem treatment on ice and therefore not essential.

Kufs' disease is the rare, adult-onset form of the neuronal ceroid-lipofuscinoses (NCL). Two clinical Kufs' phenotypes have been described, one featuring generalized tonic-clonic seizures and the other characterized by dementia. Autosomal dominant inheritance of Kufs' disease has been reported for only two families. The genetic and molecular defects underlying Kufs' disease are unknown. We report a third family with apparent autosomal dominant Kufs' disease in a family of English ancestry. Ten individuals (five men, five women) have been affected over five generations. Age of onset typically is in the fourth decade of life and is heralded by seizures. Clinical and neuropsychological assessments in several affected individuals, however, confirm the presence of dementia and follow-up evaluations suggest that dementia is the primary disabling feature of the illness. Motor abnormalities also are frequent. Neuropathological examination (three cases) documents the presence of neuronal lipopigment accumulation consistent with NCL. The combination of dementia and seizures in this and two other reported families with autosomal dominant Kufs' disease suggest that this entity represents a distinctive clinicopathological entity. Dementia is prominent but is almost always associated with generalized seizures and motoric disturbances early in the disease course. Kufs' disease should be considered in the differential diagnosis of early onset, atypical dementia.

The induction of an inflammatory response and release of cytokines such as TNF may be involved in the age-related etiology of Alzheimer disease (AD). In the brain, microglia have been shown to produce a wide variety of immune mediators, including the pro-inflammatory cytokine tumor necrosis factor (TNF). We hypothesize that with age there is increased ability of microglia to produce TNF or that age decreases the neuroprotective effect of TNF against beta-amyloid (Abeta) toxicity in neurons. We investigated the effects of Abeta(1-40) on TNF secretion from forebrain cultures of microglia from embryonic, middle-age (9-month) and old (36-month) rats. Over the first 12 hr of exposure to 10 microM Abeta (1-40), microglia from embryonic and old rats increase TNF secretion, although microglia from middle-age rats did not produce detectable levels of TNF. When low concentrations of TNF are added to neurons together with Abeta (1-40) in the absence of exogenous antioxidants, neuroprotection for old neurons is significantly less than neuroprotection for middle-age neurons. In neurons from old rats, high levels of TNF together with Abeta are more toxic than in neurons from middle-age or embryonic rats. These results are discussed in relation to neuroprotection and toxicity of the age-related pathology of AD., (Copyright 2001 Wiley-Liss, Inc.)

For a model of neurological disease and ischemia, we extended recent work to culture adult postmortem rat brain neurons. Frontal cortex sections were removed from adult rats immediately following sacrifice and at different postmortem intervals and with the brain at either 22 degrees C or 4 degrees C. Brain could be stored four times longer at 4 degrees C between sacrifice and neuronal disaggregation to achieve the same 20% recovery of live cells from those plated compared to 22 degrees C. Each milligram of rat frontal cortex was estimated by the optical disector method to contain 160,000 neurons. When cells were isolated as rapidly as possible, 9% of the neurons originally present in the brain were viable. Various postmortem intervals from 2 to 24 hr resulted in a reduction from 6% to 3% of the cells originally present. After 5 days in culture, viable neurons were 23-42% of those isolated. Neuron-like cells that survived represented 40-75% of the viable cells, or 0.5-2.75% of those originally estimated to be present in the brain. Electrophysiology experiments show that cells isolated 0 and 24 hr postmortem had neuronal electrical properties, including an average resting membrane potential of -48 mV, voltage-sensitive currents, and action potentials. Neuron-like cells were immunoreactive for neuron-specific enolase, neurofilament 200, glutamate, MAP2, and tau after 2 weeks in culture. These experiments show that neuron-like cells can be reliably cultured from adult rat cortex up to 6 hr postmortem when stored at 22 degrees C and up to 24 hr postmortem when stored at 4 degrees C. These findings should encourage donation of human postmortem brain neurons for studies on ischemia, adult pharmacology, and neurological disease., (Copyright 2001 Wiley-Liss, Inc.)

Background: This uncontrolled trial examines the safety and effects of quetiapine, a new atypical antipsychotic, in elderly patients with psychotic disorders., Method: This is an ongoing, multicenter, open-label, 52-week trial of quetiapine in men and women at least 65 years old with DSM-IV psychotic disorders. Patients received quetiapine, 25 to 800 mg/day. Assessments included the 18-item Brief Psychiatric Rating Scale (BPRS), the Clinical Global Impressions scale (CGI), the Simpson-Angus Neurologic Rating Scale, and the Abnormal Involuntary Movement Scale (AIMS)., Results: An interim analysis was performed at 12 weeks with results from 151 patients. The median total daily dose was 100 mg/day. The most common adverse events were somnolence (32%), dizziness (14%), postural hypotension (13%), and agitation (11%). Extrapyramidal symptom adverse events occurred in 6% of patients. Mean Simpson-Angus Scale total score showed significant (p<.0001) improvement at endpoint; there were no changes in AIMS scores. BPRS total and CGI-Severity of Illness scores showed significant (p<.0001 and p<.01, respectively) improvement at endpoint. No clinically important effects were reported for hematologic or liver function test variables; small changes in mean free levorotatory thyroxine (T4) levels were not associated with substantial changes in mean thyroid-stimulating hormone concentration. Mean corrected QT interval (QTc) was unchanged, but a slight increase in mean heart rate was noted., Conclusion: Quetiapine was well tolerated in a nonrandomized study of elderly patients and was associated with improvement in symptoms.

Our earlier studies had suggested a possible association between the HLA-A2 allele and Alzheimer's disease (AD). In the present study we tested the hypothesis that A2 is associated with earlier AD onset. We performed two independent studies: a collaborative study with 111 patients and a confirmatory study with 96 patients. We found similar patterns of reduced age at onset as a function of A2 in both data sets. Overall, A2 was associated with a significant 3-year shift to earlier onset. The effects of A2 and epsilon 4 on age at onset appeared additive. Our results suggest A2, or a closely linked gene, modulates onset age of AD. Association with A2 would suggest an immune/inflammatory response mechanism for AD.

Live neurons from pathological postmortem brains may provide a better model to study the molecular and cellular events associated with neurodegenerative disease. The aim of this study was to culture neurons from adult rat brain, 1 and 2 h postmortem, in typical normothermic autopsy conditions. We reliably cultured cells up to 2 h postmortem, in high yield, with neuron morphology, staining for neuronal markers (microtubule-associated protein 2, tau, and neurofilament 200). These neuron-like cells lacked glial marker staining (OX42 and glial fibrillary acidic protein). Our results suggest that neurons may be cultured from autopsy donors who have died either with or without a neurodegenerative disease such as Alzheimer or Parkinson disease.

Mild changes in neurologic function occur with aging but generally do not substantially interfere with everyday activities unless disease intervenes. Not infrequently, older adults experience minor impairment in memory, speed of cognitive processing, sleep, vision and hearing, vibratory sense in the lower extremities, and gait and posture. In general, these changes correspond with age-associated neuroanatomic changes (eg, diminished brain weight), but there is wide variability in the extent to which these changes occur. Often, "normal" neurologic changes are difficult to distinguish from impairment associated with disease.

Free and total carbamazepine (CBZ) and carbamazepine-epoxide (CBZ-EP) plasma levels were obtained on 113 patients with epilepsy (18-61 years old) controlled on either monotherapy or coadministration with either phenobarbital (PB), phenytoin (PHT), valproic acid (VPA), or all three. A subset of patients were administered tetradeuterium labeled CBZ to evaluate the effects of autoinduction and coadministration of VPA on the kinetics of CBZ and its metabolite CBZ-EP. Polytherapy had variable effect on free and total CBZ plasma levels compared to monotherapy. Coadministered PHT (co-PHT), or all three anticonvulsants together (PHT, PB, and VPA: co-AEDs) decreased free and total CBZ plasma levels. No change was noted for coadministered VPA (co-VPA). Compared to monotherapy the free and total CBZ-EP levels increased with co-VPA, less with coadministered PB (co-PB), and no change with co-PHT or co-AEDs. Protein binding of CBZ and CBZ-EP was not affected by any antiepileptic drugs studied. The free and total CBZ-EP/CBZ ratio was tripled with co-VPA or co-AED's, and doubled with co-PHT or co-PB. Isotope labeling did not demonstrate any differences in half-life (t1/2), plasma clearance (Cl), or volume of distribution (Vd). Compared to naive controls, monotherapy and co-VPA decreased CBZ t1/2 by 50%, and more than doubled the CBZ Cl without a significant change in the Vd. Autoinduction is one explanation for these changes with chronic CBZ therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of s.c. capsaicin treatment on the thoracic spinal cord contents of immunoreactive substance P (ISP), norepinephrine (NE) and serotonin (5-HT) were investigated in adult male Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Capsaicin administered s.c. significantly reduced the concentration of ISP in the thoracic spinal cords from rats of both the WKY and SHR strains. The s.c. administration of capsaicin significantly increased the NE contents of the thoracic spinal cords in rats of both the WKY and SHR strains, and both vehicle- and capsaicin-treated SHR animals exhibited significantly greater thoracic spinal cord NE concentrations than did rats from the corresponding WKY treatment groups. In contrast, s.c. capsaicin treatment significantly increased the concentration of 5-HT only in the thoracic spinal cords of SHR subjects. These results strongly suggest that the neurochemical effects of s.c. capsaicin administration on the spinal cord were not specific to ISP-containing neurons since significant changes in the concentrations of NE and 5-HT were also produced by capsaicin treatment. These capsaicin induced changes in the concentrations of putative neurotransmitter substances in the spinal cord are related to previously reported alterations in nociception and cardiovascular regulation produced by s.c. capsaicin administration. Physiological and pharmacological mechanisms possibly relating the neurochemical changes produced by capsaicin to the behavioral and cardiovascular effects of the drug previously reported are advanced and discussed.

The effect of bilateral electrolytic lesions in the nucleus reticularis giganto-cellularis (NGC) on the antinociceptive efficacy of morphine and electrical stimulation applied in the periaqueductal central gray matter (PAG) was investigated. Antinociception, evaluated by standard hot plate and tail-flick analgesiometric tests, was reliably produced by morphine (5 microgram) and focal electrical stimulation (40-200 micro A) administered in the PAG of rats via chronic indwelling cannula/electrode assemblies. Subsequent to the initial antinociceptive testing, bilateral electrolytic lesions were introduced in the NGC and the antinociceptive efficacy of morphine and stimulation in the PAG was again evaluated. Lesions in the NGC prevented the expression of the antinociception produced by the microinjection of morphine in the PAG whereas the antinociception resulting from electrical stimulation in the PAG was unaffected. Further, lesions in the NGC did not alter baseline (control) nociceptive thresholds in either analgesiometric test. These results provide additional support for involvement of the NGC in morphine-induced antinociception and, in addition, suggest that the NGC is not essential to a tonically-active inhibitory system or to the antinociception produced by focal electrical stimulation in the PAG.

The effects of s.c. capsaicin treatment on the contents of immunoreactive substance P (ISP) in several peripheral and central nervous system tissues were examined in normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Significant differences between vehicle-treated subjects of the WKY and SHR strains were observed in the ISP contents of both superior cervical and celiac sympathetic ganglia. Capsaicin pretreatment significantly reduced the ISP contents of both sympathetic ganglia in both strains. Capsaicin pretreatment significantly elevated the ISP contents of adrenal medullae only in rats of the SHR strain. The effects of s.c. capsaicin administration on the ISP contents of several selected isolated brain nuclei were also examined. No statistically significant strain or treatment differences in the SIP contents of the nucleus tractus solitarii nucleus locus ceruleus and periaqueductal central gray were observed. The ISP contents of the nucleus raphe magnus, periventricular preoptic area, and nucleus amygdaloideus medialis were significantly greater in vehicle-treated SHR rats than in vehicle-treated WKY animals. Capsaicin pretreatment significantly increased the ISP contents of both the periventricular preoptic area and nucleus amygdaloideus medialis in SHR rats. These results indicate that the effects of capsaicin treatment of the ISP contents of nervous systems tissues vary with both the tissues examined and the strain of rat. In addition, the previously reported long-lasting hypotensive effect produced by capsaicin in both the WKY and SHR strains may be related to the significant depletion of the ISP contents in peripheral sympathetic ganglia in both strains.

Effects of s.c. capsaicin pretreatment on nociception, mean systemic arterial blood pressure, and dose-response curves for depressor effects of substance P (SP) and pressor effects of angiotension II (AII) and norepinephrine (NE) were examined in normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Capsaicin pretreatment significantly elevated hot plate and tail flick latencies in SHR subjects but was without effect in WKY rats. Capsaicin pretreatment significantly reduced mean systemic arterial blood pressure in rats of both strains. Both vehicle- and capsaicin-treated WKY subjects exhibited greater depressor responses than did subjects of the corresponding SHR groups after i.v. SP administration. Vehicle-treated SHR subjects exhibited greater pressor responses to both AII and NE than did rats of the vehicle-treated WKY group. Capsaicin treatment decreased the sensitivity of WKY rats to the pressor effects of both AII and NE. Strain differences involving nociception, cardiovascular regulation, and responses to capsaicin may underly the results reported.