Alzheimer Disease: Cox C

Cox C, Albisu K. · Graduate School of Social Service, Fordham University, New York, New York, USA. · Am J Alzheimers Dis Other Demen. · Pubmed #11603163 No free full text.

Abstract: The Alzheimer's Connections Demonstration Program was designed to study the most effective ways of linking families with needed services and resources. The five-year demonstration, begun in 1995, funded case management programs in 29 Alzheimer's Association chapters and served 2,313 families. This paper reports on the final two years of the project when all programs were operational. During this period, 800 families were served. The findings indicate that the programs complement the existing chapter services by offering a specific intervention with caregivers. At the end of the demonstration, all chapters planned to continue the program as case management increased their visibility in the community through their ability to offer direct services.

Porsteinsson AP, Tariot PN, Jakimovich LJ, Kowalski N, Holt C, Erb R, Cox C. · Department of Psychiatry, Program in Neurobehavioral Therapeutics, University of Rochester Medical Center and Monroe Community Hospital, tochester, NY 14620, USA. · Am J Geriatr Psychiatry. · Pubmed #12837672 No free full text.

Abstract: OBJECTIVE: The authors describe an open-label extension of a double-blind, randomized, placebo-controlled study of divalproex sodium in 56 nursing home patients with agitation and dementia. METHODS: Participants (N=46) were treated for 6 weeks in an open fashion with clinically optimal doses of divalproex sodium (range: 250 mg/day-1,500 mg/day; mean: 851 mg/day). Behavior was assessed with the Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression of Change (CGI) by new raters. Safety, tolerability, and laboratory data were obtained regularly. RESULTS: The mean BPRS Agitation Factor decreased by 3.1 points from baseline; 86% of those completing the open phase were rated as improved on the CGI. These changes were mirrored by changes in other behavior rating scales. Sixty percent of subjects had no side effects; 33% had side effects that were rated as mild. There were no clinically significant changes in laboratory values. CONCLUSION: Ongoing open-label treatment with divalproex was associated with improvement in measures of agitation. Doses, levels, and tolerability were similar to those in the blinded phase of the study. These findings help confirm and extend the results from the placebo-controlled phase of the trial and suggest that divalproex may be beneficial for some patients with this clinical problem.

Tariot PN, Upadhyaya A, Sunderland T, Cox C, Cohen RM, Murphy DL, Loy R. · University of Rochester Medical Center, Program in Neurobehavioral Therapeutics, Monroe Community Hospital, New York, USA. · Biol Psychiatry. · Pubmed #10435208 No free full text.

Abstract: BACKGROUND: Prior work showed that administration of naloxone HCl had different behavioral effects in patients with Alzheimer's disease (AD) than controls. The aim of the present study was to contrast the physiologic and neuroendocrine responses to administration of a wide range of doses of intravenous naloxone of patients with probable Alzheimer's disease to aged-matched controls. METHODS: This was a double-blind, placebo-controlled, study of 12 patients with probable Alzheimer's disease and 8 age-matched normal controls who each received intravenous infusions of naloxone HCl on 3 different days in doses of 0.1 mg/kg and 2.0 mg/kg preceded by test doses of 0.5 mcg/kg. Order of treatment condition was randomized. Vital signs and plasma cortisol and prolactin were obtained at regular intervals. RESULTS: Both groups showed increased cortisol after naloxone 0.1 mg/kg and 2.0 mg/kg (p < .0001), but the increase was significantly greater and longer lived in controls than in patients. Patients, but not controls, also experienced a significant hypothermic response after naloxone 2.0 mg/kg (p < .05). Prolactin, heart rate, and blood pressure did not change following naloxone and did not differ between groups. CONCLUSIONS: These findings support a growing body evidence that HPA axis activity is increased in AD, and further suggest that at least part of this may be due to decreased opiatergic tonic inhibition.

Riudavets MA, Rubio A, Cox C, Rudow G, Fowler D, Troncoso JC. · Department of Neuropathology and Ophthalmic Pathology, Armed Forces Institute of Pathology, Washington, DC, USA. · J Neuropathol Exp Neurol. · Pubmed #17146288 No free full text.

Abstract: Alzheimer disease is the most common dementia in older Americans, but its impact on blacks is not clearly understood. We examined prospectively 200 autopsy brains at the Office of the Chief Medical Examiner in Maryland and compared the frequency and severity of Alzheimer lesions in blacks and whites. Histologic sections of the hippocampus and entorhinal and neocortices were immunostained for Abeta and tau proteins. Subjects were genotyped for ApoE. Abeta deposits were rated as none, sparse, moderate, or frequent; tau lesions were rated into 4 groups corresponding to Braak scores; and Abeta angiopathy was classified as present or absent. Outcome scores were treated as ordinal variables and analyzed by proportional odds logistic regression. Abeta plaques were present in 60% of black males, 58% of white males, 74% of black females, and 74% of white females. Tau lesions were present in 96% of black males, 88% of white males, 96% of black females, and 96% of white females. Neither race nor gender was a significant factor in the frequency or severity of Alzheimer lesions, and ApoE4 increased the risk for Alzheimer lesions similarly in blacks and whites.

Zamora E, Handisurya A, Shafti-Keramat S, Borchelt D, Rudow G, Conant K, Cox C, Troncoso JC, Kirnbauer R. · Department of Pathology, Division of Neuropathology, Johns Hopkins University, 720 Rutland Avenue, Baltimore, MD 21205, USA. · J Immunol. · Pubmed #16888028 links to  free full text

Abstract: Immunization with amyloid-beta (Abeta) prevents the deposition of Abeta in the brain and memory deficits in transgenic mouse models of Alzheimer's disease (AD), opening the possibility for immunotherapy of AD in humans. Unfortunately, the first human trial of Abeta vaccination was complicated, in a small number of vaccinees, by cell-mediated meningoencephalitis. To develop an Abeta vaccine that lacks the potential to induce autoimmune encephalitis, we have generated papillomavirus-like particles (VLP) that display 1-9 aa of Abeta protein repetitively on the viral capsid surface (Abeta-VLP). This Abeta peptide was chosen because it contains a functional B cell epitope, but lacks known T cell epitopes. Rabbit and mouse vaccinations with Abeta-VLP were well tolerated and induced high-titer autoAb against Abeta, that inhibited effectively assembly of Abeta(1-42) peptides into neurotoxic fibrils in vitro. Following Abeta-VLP immunizations of APP/presenilin 1 transgenic mice, a model for human AD, we observed trends for reduced Abeta deposits in the brain and increased numbers of activated microglia. Furthermore, Abeta-VLP vaccinated mice also showed increased levels of Abeta in plasma, suggesting efflux from the brain into the vascular compartment. These results indicate that the Abeta-VLP vaccine induces an effective humoral immune response to Abeta and may thus form a basis to develop a safe and efficient immunotherapy for human AD.

Murray LL, Dickerson S, Lichtenberger B, Cox C. · Department of Speech and Hearing Sciences, Indiana University, 200 S. Jordan Avenue, Bloomington, IN 47405, USA. · J Commun Disord. · Pubmed #12609577 No free full text.

Abstract: Although several clinical reports describe the benefits of toy stimulation for dementia patients, there is little empirical support for this sensory stimulation approach. The purpose of this investigation was to examine the effects of toy stimulation on the language, cognition, and emotional state of patients in the middle stages of Alzheimer's disease (AD) during a formal testing situation. Eighteen patients completed a standardized test battery and picture description task twice, once with and once without a toy stimulus present. Three AD patients completed all tasks four times (twice with and twice without the toy) to examine performance consistency. Although some patients improved their performances in the presence of a toy, there were no significant group differences between the toy and no toy conditions for any experimental measure. Of the three patients who completed experimental tasks twice in the presence of a toy, two displayed some consistent improvements whereas the remaining patient's response pattern was variable. Caregiver feedback regarding toy stimulation was positive. Methodological limitations of the current study and suggestions for future research are discussed. LEARNING OUTCOMES: As a result of reading this article, the participant will be able to: (1) summarize the previous literature regarding sensory stimulation treatment approaches for patients with Alzheimer's disease or other dementing illnesses; and (2) describe the effects of toy stimulation on the linguistic and cognitive abilities, and emotional status of patients in the middle stages of Alzheimer's disease.

Kim SY, Cox C, Caine ED. · Department of Psychiatry, University of Rochester School of Medicne and Dentistry, NY 14642, USA. · Am J Psychiatry. · Pubmed #11986134 links to  free full text

Abstract: OBJECTIVE: Ethical concerns persist over research participation of decisionally impaired persons, such as those suffering from Alzheimer's disease. Such persons may be poor judges of the burdens and risks of specific research protocols. Since even decisionally incapacitated persons cannot be enrolled in studies against their objection, their preferences convey important ethical information. The authors examined the effects of cognitive and decisional impairment on willingness to participate in research among persons with Alzheimer's disease. METHOD: Cognitive status, decision-making ability, and willingness to participate in four hypothetical research protocols of varying risk/benefit profiles were measured in 34 subjects with mild to mild/moderate Alzheimer's disease and 14 healthy elderly comparison subjects. Univariate and multivariate methods were used to analyze the effects of impairment in cognitive and decision-making abilities on willingness to participate in research. RESULTS: There were no differences in willingness to participate found between the Alzheimer's and the healthy comparison subjects for three of the four hypothetical protocols. In both groups, willingness declined as risk increased. Within the Alzheimer's disease group, the presence of greater decisional impairment tended to predict less willingness to participate in research, even after adjusting for cognitive impairment, gender, and education. CONCLUSIONS: Persons with decisional impairment due to Alzheimer's disease are as a group able to distinguish between research protocols of varying risk/benefit profiles. Because declining decision-making abilities may predict declining willingness to participate in research, informed consent procedures for Alzheimer's disease research should be sensitive to this possibility.

Podgorski CA, Lanning BD, Casaceli CJ, Nardi AL, Cox C. · University of Rochester Department of Medicine, Alzheimer's Disease Center, New York, USA. · Am J Alzheimers Dis Other Demen. · Pubmed #11831420 No free full text.

Abstract: This study was designed to determine rates of primary care physician compliance with recommendations made by physician-consultants at an Alzheimer's disease center. A mail survey was sent to primary care physicians, who were asked to indicate which recommendations had been implemented and to select reasons for lack of adherence. The response rate was 53 percent (49/92). Some 83 percent of recommendations were implemented. Compliance with medical recommendations was higher (87 percent) than with social or behavioral issues (69 percent). Reasons for noncompliance indicated that patient or family barriers were responsible in 48 percent of cases, while physicians were responsible in 24 percent. These findings validate the development of two educational programs: curricula that support the primary care physician in conveying the value of these interventions and guidelines to assist specialists in communicating treatment recommendations.

Rubio A, Vestner AL, Stewart JM, Forbes NT, Conwell Y, Cox C. · University of Rochester School of Medicine, Medical Center, Department of Pathology and Laboratory Medicine, 601 Elmwood Avenue, P.O. Box 626, Rochester, NY 14642, USA. · Biol Psychiatry. · Pubmed #11164760 No free full text.

Abstract: BACKGROUND: The single most important risk factor for Alzheimer's pathology is age. Elderly individuals are also at increased risk for suicide, but comprehensive studies of the association between Alzheimer's pathology and suicide are lacking. We designed the current study to determine if Alzheimer's disease changes are overrepresented in elderly people committing suicide. METHODS: The design is a case-control study. Cases (n = 28) were subjects older than 60 years of age who completed suicide. For each case, two age- and gender-matched individuals who died naturally were selected as control subjects (n = 56). Neuropathologic examination of hippocampal sections was performed blindly and included a modified Braak scoring system and semiquantitative assessment of neurofibrillary tangles, amyloid deposition, Lewy bodies, and Lewy-associated neurites. Data were analyzed by conditional logistic regression. RESULTS: The brains of individuals who committed suicide had higher modified Braak scores than those of matching control subjects (p =.0028). The number of neurofibrillary tangles in CA1 was not an independent predictor of suicide status in the statistical analysis (p =.16), although the distribution was more highly skewed among the cases (75th percentile of 10.5 for cases, vs. 2 for control subjects). CONCLUSIONS: Severe Alzheimer's disease pathology is overrepresented in elderly patients who complete suicide.

Tariot PN, Ogden MA, Cox C, Williams TF. · Department of Psychiatry, University of Rochester Medical Center, NY, USA. · J Am Geriatr Soc. · Pubmed #10203117 No free full text.

Abstract: OBJECTIVES: To examine the presence or absence of dementia, and the prevalence rates for different dementias, in patients with and without adult onset diabetes (AODM). DESIGN: Chart survey. SETTING: A public long-term care facility in Rochester, New York, chosen to provide an enriched sample with respect to the diseases and demographic variables of interest. PARTICIPANTS: All long-term care residents in the facility aged 50 years or older (n = 476), mean age 74.8 years. Thirty-six (7.6%) had probable Alzheimer's disease (AD), 49 (10.3%) had possible AD, 38 (8.0%) had clinically diagnosed vascular dementia, 84 (17.6%) had unspecified dementias, and 269 (56.5%) were not demented. MEASUREMENTS: Demographic data, dementia and diabetes determined on the basis of extraction of chart data, and hypertension, myocardial infarction, congestive heart failure, and hypercholesterolemia determined on the basis of chart diagnoses. RESULTS: There were 99 residents with AODM in the sample, a prevalence rate of about 21%. The rates of both dementia and AODM were as expected for this age group and setting. Patients with probable or possible AD had the lowest rates of AODM (0 and 6.1%, respectively), and patients with vascular dementia had the highest rates of AODM (47.4%). Age, sex, and race influenced both the risk of having a dementia and the type of dementia. When these variables were adjusted for in multiple logistic regression, however, AODM remained a robust predictive factor because of its significant negative association with AD. Patients with unspecified dementias and no dementia showed rates of AODM (about 20%) that were roughly comparable and intermediate between vascular dementia and AD. CONCLUSIONS: In our study, AD diagnosed clinically and AODM did not co-occur, whereas AODM was associated with vascular dementia diagnosed clinically. Conversely, in non-Alzheimer, nonvascular dementias diagnosed clinically, the rates of AODM were equivalent to those in nondemented patients. These findings are in agreement with some, but not all, previous studies.