Development, diagnosis and therapy of ketosis in non-gravid and non-lactating Guinea pigs.

BACKGROUND: Ketosis is a metabolic disorder often triggered by anorexia in animals fed on high energy diets. Although mostly described in pregnant female guinea pigs, under the name of pregnancy toxicosis; there is limited information on ketosis in males and non-pregnant females, often presented to clinics with anorexia or inappetence. The objective of this study was to observe progression of ketosis in guinea pigs, document the changes and evaluate diagnostic methods and a therapeutic approach. RESULTS: Twenty eight adult guinea pigs (Cavia porcellus), castrated males and intact females of obese and slim body condition were fasted for 3 days and refed afterwards. The slim animals served as control group for body condition. Either slim and fat animals were divided into two treatment groups: half of them received fluid replacements with glucose subcutaneously, the other half did not receive any injection and served as treatment control. Serum beta-hydroxybutyrate, and urine acetoacetate and acetone were measured during and after fasting. Serum ALT, bile acids and liver histology were also analyzed after 7 days of refeeding (and therapy). Females and obese guinea pigs showed a significantly higher increase in ketone bodies in serum and urine. Obese, female, or animals not receiving therapy needed more time to regulate ketone bodies to normal levels than slim animals, males or animals receiving therapy. Liver histology revealed increased hepatocyte degeneration and higher glycogen content in obese animals and animals receiving therapy, and additionally more glycogen content in males. Only minor hepatic fat accumulation was documented. Bile acids showed good correlation to histological liver changes whereas ALT did not. CONCLUSIONS: Female and obese animals react more intensively to fasting. As preventive management, animals should be kept in adequate body condition, fasting should be avoided, and anorexia should be treated immediately. In such a case, urinary dip sticks to detect ketone bodies are a useful diagnostic tool. Glucose therapy leads to faster cessation of ketogenesis and should be recommended in cases of ketosis. However, it needs to be adjusted to avoid hepatocyte glycogen overload and degeneration. Measuring bile acids presents a valuable indicator of liver damage.

The Extension of the German CERAD Neuropsychological Assessment Battery with Tests Assessing Subcortical, Executive and Frontal Functions Improves Accuracy in Dementia Diagnosis.

BACKGROUND/AIMS: Alzheimer's disease (AD) is the most common form of dementia. Neuropsychological assessment of individuals with AD primarily focuses on tests of cortical functioning. However, in clinical practice, the underlying pathologies of dementia are unknown, and a focus on cortical functioning may neglect other domains of cognition, including subcortical and executive functioning. The current study aimed to improve the diagnostic discrimination ability of the Consortium to Establish a Registry for Alzheimer's Disease - Neuropsychological Assessment Battery (CERAD-NAB) by adding three tests of executive functioning and mental speed (Trail Making Tests A and B, S-Words). METHODS: Logistic regression analyses of 594 normal controls (NC), 326 patients with mild AD and 224 patients with other types of dementia (OD) were carried out, and the area under the curve values were compared to those of CERAD-NAB alone. RESULTS: All comparisons except AD-OD (65.5%) showed excellent classification rates (NC-AD: 92.7%; NC-OD: 89.0%; NC-all patients: 91.0%) and a superior diagnostic accuracy of the extended version. CONCLUSION: Our findings suggest that these three tests provide a sensible addition to the CERAD-NAB and can improve neuropsychological diagnosis of dementia.

Establishing robust cognitive dimensions for characterization and differentiation of patients with Alzheimer's disease, mild cognitive impairment, frontotemporal dementia and depression.

OBJECTIVE: The diagnosis of mild cognitive impairment (MCI) and dementia requires detailed neuropsychological examinations. These examinations typically yield a large number of outcome variables, which may complicate the interpretation and communication of results. The purposes of this study were the following: (i) to reduce a large data set of interrelated neuropsychological variables to a smaller number of cognitive dimensions; (ii) to create a common metric for these dimensions (z-scores); and (iii) to study the ability of the cognitive dimensions to distinguish between groups of patients with different types of cognitive impairment. METHODS: We tested 1646 patients with different forms of dementia or with a major depression with a standard (n = 632) or, if cognitively less affected, a challenging neuropsychological battery (n = 1014). To identify the underlying cognitive dimensions of the two test batteries, maximum likelihood factor analyses with a promax rotation were conducted. To interpret the sum scores of the factors as standard scores, we divided them by the standard deviation of a cognitively healthy sample (n = 1145). RESULTS: The factor analyses yielded seven factors for each test battery. The cognitive dimensions in both test batteries distinguished patients with different forms of dementia (MCI, Alzheimer's dementia or frontotemporal dementia) and patients with major depression. Furthermore, patients with stable MCI could be separated from patients with progressing MCI. Discriminant analyses with an independent new sample of patients (n = 306) revealed that the new dimension scores distinguished new samples of patients with MCI from patients with Alzheimer's dementia with high accuracy. CONCLUSION: These findings suggest that these cognitive dimensions may benefit neuropsychological diagnostics.

Neuropsychological signs of Alzheimer's disease 8 years prior to diagnosis.

We investigated the earliest neuropsychological changes in Alzheimer's disease (AD) by comparing the baseline performance of 29 individuals who subsequently developed AD within an average of 7.91 ± 2.70 years with 29 pairwise-matched individuals who remained cognitively healthy (NC). We hypothesized that subtle, qualitative changes in cognition precede clinical AD by several years, and therefore examined subjective as well as standard quantitative measures of cognition, in addition to subjective estimates of mood and medical status. Participants were selected from the 825 members of the longitudinal BASEL study (BAsel Study on the ELderly), all of whom had been ApoE-genotyped and received comprehensive bi-annual neuropsychological assessments. Within 13 years, 29 were diagnosed with probable AD. Each individual who progressed to AD (AD-P) was pairwise matched to a NC participant based on age, education, demographic status, observation period, and, importantly, ApoE genotype. A regression analysis using the lasso technique identified which of 115 neuropsychological variables best discriminated baseline NC from baseline AD-P performance. This analysis yielded eleven neuropsychological variables that optimally discriminated the two groups (correct classification rate: 60.4%): 1) Intrusions and 2) response bias in verbal learning and memory tasks; 3) delayed figure recall; 4-6) three Wechsler Adult Intelligence Scale (WAIS) Block Design subtest variables; 7-8) number of errors and repetitions on letter fluency; and 9-11) self-report of memory problems, a feeling of sadness, and cardiac problems. These results suggest that the preclinical neuropsychological cascade to AD includes subtle but identifiable qualitative impairments in verbal and visual memory, visuospatial processing, error control, and subjective neuropsychological complaints.

Evaluation of intratester and intertester reliability of the Constant-Murley shoulder assessment.

This study evaluated the reliability of the Constant-Murley Score. Two testers assessed 63 patients twice on the same day using the original publication by Constant and Murley. The intratester reliability of the total score was high and the differences between the tests were small; 2 of 14 items were unreliable. The intertester reliability was high, but there were significant median differences of the total score; 12 of 14 items were unreliable. We believe that the differences between the testers were due to the brief explanations of test components in the original publication. The reliability of the Constant-Murley Score could possibly be improved by a better standardization of the assessment procedure.