Alzheimer's disease and co-morbidity: increased prevalence and possible risk factors of excess mortality in a naturalistic 7-year follow-up.

BACKGROUND: Subjects with late-onset Alzheimer's disease (AD) have to be sufficiently healthy to live long enough to experience and to be diagnosed with dementia in later life. In contrast, neurodegeneration and cognitive deficits in AD may increase the frequency of co-morbid disorders and their possible influence on mortality. Consequently, we investigated whether the pattern of co-morbidity and its relevance for later death differed between hospitalized AD and age-matched controls subjects. METHODS: Co-morbid diseases with a prevalence of more than 1% at hospital admission were compared between 634 hospitalized AD and 72,244 control subjects aged above 70 years admitted to the University of Birmingham NHS Trust between 1 January 2000 to 31 December 2007. Risk factors, i.e. co-morbid diseases that were predictors of mortality within the 7-year follow-up, were identified and compared. RESULTS: Subjects with AD suffer more eating disorders, infections, brain diseases and neck of femur fractures than other hospitalized elderly patients. In contrast, some cardiovascular diseases and diabetes mellitus were less prevalent in AD subjects in comparison with hospitalized controls. Diseases that might have contributed to later mortality in AD were pneumonia, ischemic heart disease and gastroenteritis, but there were no significant differences in their impact on mortality compared to other hospitalized elderly subjects with the same co-morbidities in multivariate logistic regression analyses. CONCLUSION: Patients with AD have a different pattern of co-morbidity, but die from the same diseases as other hospitalized patients. Infections including pneumonia and diseases that may occur secondary to neurodegeneration and cognitive decline may need special attention in patients with AD who may not be able to identify or report the early symptoms. Preventive measures may be helpful to reduce the high risk and fatal consequences of undetected disease in AD.

Type-2 diabetes mellitus in schizophrenia: increased prevalence and major risk factor of excess mortality in a naturalistic 7-year follow-up.

OBJECTIVE: Physical co-morbidity including type 2 diabetes mellitus is more prevalent in patients with schizophrenia compared to the general population. However, there is little consistent evidence that co-morbidity with diabetes mellitus and/or other diseases leads to excess mortality in schizophrenia. Thus, we investigated whether co-morbidity with diabetes and other somatic diseases is increased in schizophrenics, and if these are equally or more relevant predictors of mortality in schizophrenia than in age- and gender-matched hospitalised controls. METHODS: During 2000-2007, 679 patients with schizophrenia were admitted to University Hospital Birmingham NHS Trust. Co-morbidities were compared with 88,778 age- and gender group-matched hospital controls. Predictors of mortality were identified using forward Cox regression models. RESULTS: The prevalence of type 2 diabetes mellitus was increased in schizophrenia compared to hospitalised controls (11.3% versus 6.3%). The initial prevalence of type 2 diabetes mellitus was significantly higher in the 100 later deceased schizophrenic patients (24.0%) than in those 579 surviving over 7 years (9.2%). Predictors of mortality in schizophrenia were found to be age (relative risk [RR] = 1.1/year), type 2 diabetes mellitus (RR = 2.2), pneumonia (RR = 2.7), heart failure (RR = 2.9) and chronic renal failure (RR = 3.2). The impact of diabetes mellitus on mortality was significantly higher in schizophrenia than in hospital controls (RR = 2.2 versus RR = 1.1). In agreement, deceased schizophrenics had significantly suffered more diabetes mellitus than deceased controls (24.0 versus 10.5%). The relative risks of mortality for other disorders and their prevalence in later deceased subjects did not significantly differ between schizophrenia and controls. CONCLUSION: Schizophrenics have more and additionally suffer more from diabetes: co-morbidity with diabetes mellitus is increased in schizophrenia in comparison with hospital controls; type 2 diabetes mellitus causes significant excess mortality in schizophrenia. Thus, monitoring for and prevention of type 2 diabetes mellitus is of utmost relevance in hospitalised patients with schizophrenia.

Apolipoprotein E allele 4 is not a sufficient or a necessary predictor of the development of Mild Cognitive Impairment.

The presence of Mild Cognitive Impairment (MCI) and of an apolipoprotein E (apoE) varepsilon4 allele both predict the development of Alzheimer's disease. However, the extent to which this allele also predicts the development of MCI is unclear even though MCI is an early transitional stage in the development of Alzheimer's disease. The present study investigates the prevalence of the apoE varepsilon4 allele in incipient MCI. Participants were recruited from the population-based Leipzig Longitudinal Study of the Aged (LEILA75+). All subjects who were initially cognitively healthy, i.e. did not meet MCI criteria described by Petersen [Petersen RC. Mild cognitive impairment. J Intern Med 2004; 256(3): 183-94], and whose apoE status could be determined were followed-up. After 4.5 years, 15.5% of the cognitively healthy target population had developed MCI. The frequencies of the apoE varepsilon4 genotype did not differ between individuals with incipient MCI (12.9%) and individuals who remained cognitively healthy during the study (18.4%, p>0.5). Consequently, the apoE varepsilon4 genotype is not a necessary or sufficient risk factor for MCI. Further studies need to investigate the influence of the whole range of genetic and environmental risk factors on the course of Alzheimer's disease including the initial development of MCI and the later conversion to Alzheimer's disease.