The apolipoprotein E allele epsilon 4 is overrepresented in patients with the Lewy body variant of Alzheimer's disease

We determined apolipoprotein E (ApoE) genotypes in 122 autopsied demented patients. The frequency of the ApoE epsilon 4 allele was 39.6% in Alzheimer's disease (AD), 29.0% in the Lewy body variant of AD (LBV), and 6.25% in diffuse Lewy body disease. For AD and LBV patients, the epsilon 4 frequency was significantly higher than that reported in nondemented controls (10 to 15%). Therefore, LBV and AD share ApoE epsilon 4 as a genetic risk factor, providing further evidence that these conditions overlap.     

High frequency of apolipoprotein E epsilon4 allele in young individuals with very mild Alzheimer's disease-related neurofibrillary changes

The pathological process of initial neurofibrillary (NF) changes underlying Alzheimer's disease (AD) represents the early preclinical phase of the disease. In a small percentage of individuals, these initial NF changes (Braaks' stage I of six stages) may develop at a surprisingly young age. The aim of this study was to determine the impact of apolipoprotein E (ApoE) on the development of such initial NF changes in young individuals. To this end, the ApoE genotypes were determined using a seminested polymerase chain reaction assay followed by restriction isotyping in young individuals (n = 44; mean age of 38 years) with initial NF changes (stage I). The results were compared with ApoE genotypes of age-matched controls (n = 70) devoid of such changes (stage 0). Stage I cases exhibited a significantly higher epsilon4 allele frequency compared to controls (0.18 vs 0.09, P = 0.039). Thus, the present study reveals an association of epsilon4 allele with the early onset of AD-related NF changes in young individuals. This finding underlines the relevance of the asymptomatic phase in the course of AD.     

Lipoproteins in clinical laboratory medicine]

The characteristics and metabolism of lipoproteins were reviewed. Apolipoproteins has been studied in the fields of neurological diseases as well as hyperlipidemia. A highly significant association between apolipoprotein E (ApoE) epsilone 4 allele and late-onset familial and sporadic Alzheimer's disease (AD) was reported. The recent studies also described the following: (1) late-onset familial AD linked to the proximal long arm of chromosome 19; (2) the presence in the CSF of several proteins, one of which was ApoE, what bound to immobilized amyloid beta-peptide (beta A4) with high avidity; and (3) staining by antisera to ApoE of senile plaques, neurofibrillary tangles, and cerebral vessel amyloid deposits in AD brains. Furthermore, (4) both purified ApoE isomers, ApoE3 and ApoE4, bound to beta A4 synthetic peptide, forming a complex that resisted dissociation by boiling in sodium dodecyl sulfate, but the isomers showed different kinetics in doing so: binding by ApoE4 was observed in minutes, while binding by ApoE3 required hours; and (5) ApoE4 did not bind to beta A4 peptide at pH less than 6.6, while ApoE3 bound to beta A4 peptide from pH7.6 to 4.6. We studied ApoE phenotype expression and the corresponding allele frequencies (epsilon 2, epsilon 3 and epsilon 4) in Japanese patients with late-onset sporadic AD. The frequency of the ApoE epsilon 4 allele was obviously high in AD patients compared with the controls, but it was not different between vascular dementia patients and the controls. These results suggest that ApoE isoforms may play a functional role in the pathophysiology of late-onset familial and sporadic AD and that the isoform-specific difference in beta A4 binding may be involved in forming the AD lesion.     

Outcome of chromosomally normal livebirths with increased fetal nuchal translucency at 10-14 weeks'' gestation

Argyrophilic grain disease (AGD) is a distinct degenerative disorder of the human brain associated with the formation of abnormally phosphorylated tau protein. AGD-related cytoskeletal changes are known to affect specific subsets of nerve cells and oligodendrocytes. Here we demonstrate a remarkable association between the apolipoprotein E (ApoE) epsilon2 allele and AGD. Individuals afflicted with AGD (n = 48) reveal a significantly higher frequency of the epsilon2 allele compared with controls (n = 43) (22% versus 4%, P < 0.0002). The association between AGD and epsilon2 allele of ApoE suggests that AGD can be distinguished from other neurodegenerative disorders not only neuropathologically, but also genetically.     

Apolipoprotein E phenotype and cognitive decline in a prospective study of elderly community women

OBJECTIVE: To determine whether apolipoprotein E (Apo E) phenotype is associated with cognitive decline in community-dwelling nondemented elderly women. DESIGN: Prospective cohort study. SETTING: A university-affiliated clinic near Pittsburgh, Pa. PATIENTS: A total of 1750 nondemented community-dwelling women, aged 65 years and older, who were enrolled in the Study of Osteoporotic Fractures. MAIN OUTCOME MEASURES: The women completed a baseline interview and performed 3 cognitive tests: the modified Mini-Mental State Examination, Trials B, and Digit Symbol. Serum samples were obtained for Apo E typing. Baseline cognitive scores and repeated scores approximately 6 years after study enrollment were compared in women with and without Apo E epsilon 4. Cognitive decline, defined as the worst 10th percentile change scores, was assessed for each test and by phenotype group. RESULTS: After adjustment for age, education, presence of severe tremor, and depression, baseline scores did not differ by Apo E epsilon 4 status except for lower scores on Trails B in the homozygous epsilon 4 group (mean score, 159.7 compared with 127.7 for the heterozygous epsilon 4 group and 125.4 for the no epsilon 4 group; P = .01). However, repeated test performance on follow-up examination was worse on all tests in those women with 1 or more epsilon 4. Reduction on the modified Mini-Mental State Examination was 0% for no epsilon 4 allele, 1.9% for 1 epsilon 4 allele, and 3.7% for 2 epsilon 4 alleles (P < .001); reduction on Digit Symbol was 6.2% for no epsilon 4 allele, 9.0% for 1 epsilon 4 allele, and 17.5% for 2 epsilon 4 alleles (P = .04); and reduction on Trials B was 5.9% for no epsilon 4 allele, 25.0% for 1 epsilon 4 allele, and 10.9% for 2 epsilon 4 alleles (P = .002). Women with at least 1 epsilon 4 had an odds ratio of 1.6 (95% confidence interval, 1.1-2.3) of having cognitive decline during the study period. CONCLUSION: Apolipoprotein E epsilon 4 is associated with cognitive decline in community-dwelling nondemented women.     

Glomerular filtration rate and kidney size after six years disease duration in non-insulin-dependent diabetic subjects

To evaluate the association of TNFB NcoI polymorphism with SLE in the Korean population, we investigated the frequencies of the TNFB and HLADRB1 alleles in 281 controls and 97 SLE patients, including 56 patients with nephritis and 41 patients without nephritis. The frequency of the TNFB*2 homozygote in SLE was significantly increased over controls (43.3% vs 28.5%, RR = 1.9,p < 0.01). In SLE with nephritis, the TNFB*2 homozygote was more significantly increased (57.1% vs 28.5%, RR = 3.4,p < 0.0001), whereas there was no significant difference between SLE without nephritis and controls. The study of HLA-DRB 1 alleles revealed the increased frequencies of DRB1*02 and *03 (30.9% vs 18.2%, RR = 2.0,p < 0.01; 8.2% vs 2.1%, RR = 4.1,p < 0.05). There was no significantly different distribution of HLA-DRB1 alleles between SLE patients with nephritis and without nephritis. We found positive LD between TNFB*1 and HLA-DR1B1*13, and between TNFB*2 and the particular DRB1 allele: *15, *04, and *07 in controls and/or in SLE patients. After stratification for each HLADRB1 allele, SLE with nephritis showed a higher frequency of TNFB*2 homozygote compared with the corresponding controls in DRB1*15, *08, and *09 positives. Our results suggest that the TNFB*2 homozygote may be a strong susceptibility gene of SLE with nephritis in the Korean population.     

Laparoscopic management of a noncommunicating uterine horn in a patient with an acute abdomen

INTRODUCTION: The presence of the apolipoprotein E4 allele (apoE4) has been recognized as a risk factor for the development of presenile and senile forms of Alzheimer's dementia (AD). MATERIAL AND METHODS: The apoE alleles frequency of 71 normal controls (NC), 60 demented controls (DC) and 50 senile type AD subjects was determined by polymerase chain reaction in order to get data about the apoE polymorphism of the Hungarian AD population. RESULTS: The apoE3/3 genotype was the most common in all groups. The apoE4 frequency was significantly higher (28%) in the AD group than that was (7% and 9%) in the NC and DC populations, respectively. No apoE4 homozygotes were found in the DC group and the number of heterozygotes was lower in the DC than in the AD group. CONCLUSION: The results are in good agreement with others in the literature and support the occurrence of an increased apoE4 allele frequency in Hungarian senile AD population.     

Alzheimer's disease: interaction of apolipoprotein E genotype, family history of dementia, gender, education, ethnicity, and age of onset

We evaluated 197 patients with predominantly late-onset Alzheimer's disease (AD) who belonged to several ethnic groups and analyzed the relationship of age of onset of AD to the presence or absence of several risk factors in this entire group of patients. The apolipoprotein E (apoE) epsilon 4 allele frequency, which was 29% in all patients (compared with the reported population mean of 13.7%, p < 0.001, did not vary significantly between ethnic groups but declined significantly with increasing age. The apoE epsilon 2 allele frequency was 3%, compared with the reported population mean of 7.4% (p = 0.001). The frequency of a positive family history of dementia in first-degree relatives (FH +) (overall 45%) did not vary significantly between ethnic groups. ApoE epsilon 4-positive (epsilon 4+) patients tended to have a higher FH + rate (58%) than apoE epsilon 4-negative (epsilon 4-) patients (40%) (p = 0.02). When the potential risk factors of gender, education, FH+ status, and epsilon 4+ status were examined together in a multiple linear-regression analysis, FH+ and epsilon 4+ status (but not gender or education) were significant (they were both associated with an earlier age of onset of AD). In a post-hoc analysis, we found a reduced age of onset in women, but not men, who were both FH + and epsilon 4+. Additionally, those probands who were epsilon 4+ were more likely to inherit the disease from their mothers than their fathers. The mechanism by which epsilon 4+ and FH+ status operate as risk factors may be by their effect on the age of onset of AD.     

Apolipoprotein E epsilon 4 allele distribution in Wernicke-Korsakoff syndrome with or without global intellectual deficits

Recent genetic studies show that the apolipoprotein E (ApoE) epsilon 4 allele is a risk factor for Alzheimer's disease (AD). Whether this allele is associated with other dementing diseases is the next important question. The information could provide a clue to the pathogenetic role of ApoE. In the present study, patients with Wernicke-Korsakoff syndrome (WKS) of alcoholic etiology were divided into two groups according to the severity of intellectual deficits, i.e., those of "classical" Korsakoff patients with preserved intellectual function other than amnesia and those with global intellectual deficits. Genotyping showed that the frequency of ApoE epsilon 4 allele was significantly higher in the patients with global deficits, suggesting the involvement of this allele in the intellectual decline of WKS. In contrast, distributions of other two markers, alpha 1-antichymotrypsin and presenilin-1, did not differ between the two groups. These results added further support to the notion that the consequence of acute insult to the brain is influenced by the ApoE genotype, and suggested ApoE's role in the development of a certain group of "alcoholic dementia."     

CYP2D6 allelic frequencies in young-onset Parkinson's disease

Parkinson's disease (PD) is thought to develop as a result of interactions between genetic susceptibility factors and environmental exposures. One candidate gene is CYP2D6, which codes for the debrisoquine 4-hydroxylase cytochrome P450. Impairment of debrisoquine 4-hydroxylase activity has been associated with an increased risk of PD in patients with younger age at disease onset. Genotyping studies in patients with an older age at onset have reported modest increases in risk associated with the CYP2D6 B and A alleles; however, the risk for young-onset PD has not been adequately evaluated. We designed a case-control study to investigate the role of nonfunctional CYP2D6 allelic risk factors for young-onset PD in a sizable patient population and compared the distributions of CYP2D6 genotypes between young-onset ( < or = 51 years) PD patients (n = 108) and controls (n = 236). In contrast with the results from genotyping studies conducted among patients with an older age at onset, there were no significant differences in CYP2D6 allelic frequencies between young-onset PD cases and controls. The frequency of the B allele was slightly lower in the young-onset PD cases than in the controls (0.14 versus 0.20) (X2 = 2.66, p = 0.10). The presence of one or more B alleles was not associated with an increased risk of young-onset PD (odds ratio 0.58; 95% CI 0.33 to 1.00), nor was the presence of one or more nonfunctional alleles (i.e., A, B, D, and D2) (odds ratio 0.68; 95% CI 0.41 to 1.13). This study suggests that the young-onset PD population may differ from the older-onset population with respect to risk factors.     

Prevalence of associated diseases in different types of dementia among elderly institutionalized patients: analysis of 3447 records

OBJECTIVE: To determine the prevalence of dementia in a population of hospitalized or institutionalized elderly patients, and that of associated diseases according to dementia type. DESIGN: Retrospective analysis of a database of diagnostic codes. SUBJECTS: All patients admitted to 1 of the 4 geriatric units participating in the study at the Charles Foix Hospital between 1980 and 1989. MEASUREMENTS: All diagnoses mentioned in the discharge summary that could cause or contribute to hospitalization were recorded for each patient. A final list of 54 different diagnoses could be recorded for each patient. Dementia was subdivided into 3 subtypes: Alzheimer dementia (DAT), vascular dementia (VD), and other types of dementia (unclassifiable dementia). MAIN RESULTS: The study involved 3447 patients aged 81.0 +/- 8.3 years, of whom 27.7% were men. Dementia was the most frequent disease in this population (34.3%); Alzheimer disease was responsible for 15%, vascular dementia for 9.5%, and other types for 9.8%. The average number of associated diseases was 3.23 +/- 2.10 in the Alzheimer dementia group, 4.73 +/- 2.38 in the vascular dementia group, and 3.96 +/- 2.26 in the nondemented group. Parkinson disease was present in 15.5% of patients with unclassifiable dementia, compared with 7.6% in the nondemented group (P < 0.001). There were significantly more diseases commonly seen in bedridden patients in the group of patients with both other types of dementia and Parkinson disease than in the group of other types of dementia patients without Parkinson disease (P < 0.01). CONCLUSION: Dementia was the most common disease observed in our elderly institutionalized population. Alzheimer patients had significantly fewer associated diseases than nondemented patients, whereas the reverse was found in the vascular dementia group. The co-existence of Parkinson disease and dementia in our population was associated with the poorest health status, as these patients were more likely to present simultaneously such conditions as pressure sores, incontinence, dehydration, or iatrogenesis.     

Apolipoprotein E polymorphism in elderly east Africans

Current advances have shown the apolipoprotein E (APOE)-epsilon 4 allele to be highly associated with late-onset familial and sporadic Alzheimer's disease (AD) in Western populations. The association of APOE allele frequencies and dementia remain unknown in populations from developing countries. We recently initiated a project to examine APOE frequencies in non-demented and demented elderly East Africans. Blood DNA collected from two hospital-based populations showed that the APOE allele frequencies in a group of non-demented 67 Tanzanians over the age of 65 years were found to be 14% for epsilon 2, 61% for epsilon 3 and 25% for epsilon 4. By comparison, the frequency of APOE-epsilon 4 in an age-matched demented group was also 25%. Assessment of APOE genotypes in the group of elderly Kenyan subjects from Nairobi also revealed high frequencies of the epsilon 4 allele with no clear difference in frequency between demented and non-demented subjects. Our preliminary observations suggest that elderly East Africans with no apparent clinical AD possess relatively high APOE-epsilon 4 allele frequencies compared to normal ageing subjects from Western countries including African-Americans. These results appear similar to those reported in a recent study in Nigerian Africans where a lack of correlation between APOE-epsilon 4 allele frequency and Alzheimer type of dementia was noted, and imply that APOE-epsilon 4 allele may not necessarily be a risk factor in some populations of Africa.     

Apolipoprotein E-associated risk for Alzheimer's disease in the African-American population is genotype dependent

As a part of our ongoing study on Alzheimer's disease (AD) in elderly African Americans, we obtained clinical assessment and apolipoprotein E (ApoE) genotype data on 288 individuals (including 60 with AD). The ApoE epsilon4 allele frequency was significantly increased in AD patients compared with controls. The age-adjusted odds ratio (OR) for AD in epsilon4 homozygotes was 4.83 (95% confidence interval [CI], 1.71-13.64) compared with the epsilon3/epsilon3 genotype, but the OR for AD with the epsilon3/epsilon4 genotype did not reach significance (1.20; 95% CI, 0.58-2.45). These findings suggest that the association between ApoE epsilon4 and AD is weaker in African Americans than in whites.     

Clinical and genetic characteristics of type 2 diabetes with and without GAD antibodies

The aim of the study was 1) to establish the prevalence of GAD antibodies (GADab) in a population-based study of type 2 diabetes in western Finland, 2) to genetically and phenotypically characterize this subgroup, and 3) to provide a definition for latent autoimmune diabetes in adults (LADA). The prevalence of GADab was 9.3% among 1,122 type 2 diabetic patients, 3.6% among 558 impaired glucose tolerance (IGT) subjects, and 4.4% among 383 nondiabetic control subjects. Islet antigen 2 antibodies (IA2ab) or islet cell antibodies were detected in only 0.5% of the GADab- patients. The GADab+ patients had lower fasting C-peptide concentrations (median [interquartile range]: 0.46 [0.45] vs. 0.62 [0.44] nmol/l, P = 0.0002) and lower insulin response to oral glucose compared with GADab- patients. With respect to features of the metabolic syndrome, the GADab+ patients had lower systolic (140 [29.1] vs. 148 [26.0] mmHg, P = 0.009) and diastolic (79.2 [17.6] vs. 81.0 [13.1] mmHg, P = 0.030) blood pressure values, as well as lower triglyceride concentrations (1.40 [1.18] vs. 1.75 [1.25] mmol/l, P = 0.003). GADab+ men had a lower waist-to-hip ratio compared with GADab- patients. Compared with GADab- patients and control subjects, the GADab+ patients had an increased frequency HLA-DQB1*0201/0302 (13 vs. 4%; P = 0.002) and other genotypes containing the *0302 allele (22 vs. 12%; P = 0.010). However, the frequency of these high-risk genotypes was significantly lower in GADab+ type 2 patients than in type 1 diabetes of young or adult onset (0201/0302 or 0302/X: 36 vs. 66 vs. 64%, P < 0.001). The GADab+ type 2 group did not differ from control subjects with respect to genotypes containing the protective DQB1-alleles *0602 or *0603, nor with respect to the type 1 high-risk genotype in the IDDM1 (Hph1 +/+). We conclude that GADab+ patients differ from both GADab- type 2 diabetic patients and type 1 diabetic patients with respect to beta-cell function, features of the metabolic syndrome, and type 1 diabetes susceptibility genes. Further, we propose that LADA be defined as GADab positivity (>5 relative units) in patients older than 35 years at onset of type 2 diabetes.     

Psychopathology in younger versus older persons with very mild and mild dementia of the Alzheimer type

OBJECTIVE: The psychopathology associated with early-onset dementia of the Alzheimer type was investigated by comparing the prevalence of psychiatric symptoms in younger subjects (mean age = 59 years) who had very mild or mild dementia with that in older adults (mean age = 72) whose dementia was of equivalent severity. METHOD: Nondemented comparison subjects and persons with very mild or mild dementia of the Alzheimer type were recruited to participate in longitudinal studies. All subjects met strict inclusion and exclusion criteria. Information pertaining to personality changes, affective symptoms, and psychotic symptoms was included in the 90-minute semistructured, physician-administered interview, which was used to assign a clinical dementia rating according to published guidelines. The younger group were age 64 or younger and consisted of 20 nondemented subjects, 11 subjects with very mild dementia, and 18 subjects with mild dementia. The older group, described previously, were 64-83 years old and consisted of 83 nondemented subjects, 41 persons with very mild dementia, and 68 subjects with mild dementia. RESULTS: The psychopathology in the younger subjects was similar to that in the older group. Personality changes occurred in over 80% of the younger persons with very mild illness. Psychotic symptoms were present in over 40% of the younger persons with mild illness but were rare in the group with very mild dementia. CONCLUSIONS: Similar patterns of psychopathology in younger and more elderly persons with dementia of the Alzheimer type support the suggestion that these changes are direct effects of the illness on the CNS. Increased attention to documenting these noncognitive symptoms and studying various treatments is urgently needed.     

Catalytic properties of the purified rat hepatic cytosolic cholesteryl ester hydrolase

Alzheimer's disease (AD) is a heterogeneous entity presenting as sporadic and familial disease. In familial AD, there is evidence for genetic linkage to a yet undefined gene on chromosome 14 in early-onset pedigrees and on chromosome 19 in late-onset pedigrees. In a few early-onset kindreds, there were mutations in the amyloid precursor gene on chromosome 21. There is an increased frequency of apolipoprotein E (ApoE) epsilon4 allele in patients with late-onset AD. We studied the clinical presentation and profile of cognitive deficits in 58 AD patients at the early stage of the disease. We divided the AD patients into subgroups of sporadic late-onset (SLO) (> or = 65 years), familial late-onset (FLO) (> or = 65 years), sporadic early-onset (SEO) (<65 years), and familial early-onset (FEO) (<65 years) patients and into three subgroups according to their ApoE genotype zero epsilon4, one epsilon4, and two epsilon4 alleles. The AD subgroups did not differ in the global clinical severity of dementia or the duration of the disease. SLO, FLO, SEO, and FEO subgroups did not differ in clinical characteristics such as occurrence of rigidity, hypokinesia, tremor, myoclonus, hallucinations, delusions, or epileptic seizures nor in the profile of deficits on tests assessing memory, language, visuospatial, executive, and praxic functions. The epsilon4++ allele frequency was 0.43 for all AD patients and did not differ across subgroups divided according to the familial aggregation and age of onset. Patients with two epsilon4 alleles had earlier age at onset of dementia than those with no epsilon4 allele (63 +/- 9 versus 68 +/- 9 years), but otherwise the clinical symptoms and signs were not related to the ApoE genotype. However, the AD patients with two epsilon 4 alleles had lowest scores on memory tests and differed significantly from those with one or zero epsilon4 allele in the delayed list learning (p<0.05) and from those with zero epsilon4 allele in the immediate and delayed story recall. In contrast, verbal functions were better preserved in two epsilon4 patients than in those with other ApoE genotypes. This study failed to confirm the earlier reports of severe aphasia, agnosia, and apraxia in familial AD patients, but the clinical phenotype was similar irrespective to the familial aggregation. However, AD patients with two epsilon4 alleles are characterized by more severe memory loss and earlier age of onset than those without the epsilon4 allele.     

Dementia in the very elderly. Results of the Berlin Aging Study

The frequency of dementia in very old subjects, the risk factors and the consequences of the disease were investigated in the Berlin Aging Study in an age- and gender-stratified design (ages 70-103 years, n = 516). Psychiatrists diagnosed a dementia syndrome according to DSM-III-R, applying the GMS-A and HAS interviews. The dementia frequency steeply increases until the 90-94 year group, but there is no further exponential increase for the 95+ group--instead for men the data show a plateau of dementia prevalence. Low education level turned out to be a risk factor, which explains the gender effect in a logistic regression analysis. The apolipoprotein E4 genotype was confirmed as a risk factor--however, only for the older subjects (85+). Dementia was a major reason for institutionalization. The 2-year mortality was no higher in dementia than for age-matched non-demented controls. The results gave a detailed picture of dementia in the very old. This is a prerequisite for planning facilities for psychiatric diagnostics and therapy as well as nursing care.     

Longitudinal weight changes, length of survival, and energy requirements of long-term care residents with dementia

OBJECTIVE: We hypothesized that institutionalized patients with dementia, who frequently have feeding problems and require supervised and assisted feeding, would lose more weight during their residency than nondemented, independently functioning residents and have compromised survival. To test this hypothesis, we examined the survival and longitudinal changes in weight of two cohorts of institutionalized residents with dementia and compared these cohorts with a cohort of nondemented residents. We also measured the resting energy expenditures of a subset of the subjects with dementia as an indicator of their energy needs. DESIGN: A longitudinal cohort study with retrospective baseline chart review and subsequent follow-up of monthly weights and mortality over 4 years. SETTING: A 725-bed long-term care institution with specified levels of care. SUBJECTS: Two cohorts of residents with dementia, one consisting of subjects who required total care throughout their institutional stay (n = 31) and another group who did not initially require total care (n = 48); these were compared with a cohort with normal mentation who were functionally independent in their daily activities (n = 26). The total number of subjects was 105. MEASUREMENTS: Demographics, medical problems, and medications by chart review; functional and mental status evaluations; longitudinal monthly weights and mortality for the 48-month study period; and resting energy expenditures by indirect calorimetry. MAIN RESULTS: Residents with dementia had lower weights on admission and throughout their stay than nondemented, independently functioning residents, and they were more likely to have a weight loss of 10 lbs or more at some point during the 4-year study period. However, their mean weights did not change during the study period. The mean survival from admission of those demented residents who died was more than 3 years. Resting energy expenditures of women residents with advanced dementia were 12% lower than predicted from the Harris Benedict equations. CONCLUSION: Dementia is not necessarily associated with unremitting weight loss during institutionalization despite the frequent occurrence of feeding difficulties and temporary weight loss. This may be caused partly by the lower than expected resting energy expenditures and, hence, energy needs of affected residents as their dementia progresses. Demented residents weighed significantly less than nondemented, independently functioning residents throughout their institutional stay. Nevertheless, nursing staff are able to maintain weight and survival for extended periods even in very impaired residents.     

Apolipoprotein E epsilon4 allele as a genetic risk factor for left ventricular failure in homozygous beta-thalassemia

In homozygous beta-thalassemia, the organ damage is mainly attributed to excessive iron deposition through the formation of oxygen free radicals. Despite appropriate transfusion and chelation therapy and low ferritin levels, patients still develop organ failure, heart failure being the main cause of death. This study was designed to determine whether the decreased antioxidant activity of the apolipoprotein E (APOE) 4 allele could represent a genetic risk factor for the development of left ventricular failure (LVF) in beta-thalassemia homozygotes. A total of 251 Greek beta-thalassemia homozygotes were studied. Patients were divided in three groups: group A (n = 151) with no cardiac impairment, group C (n = 47) with LVF, and 53 patients with LV dilatation and normal LV systolic function constituted the group B. DNA was obtained from all patients, and the polymerase chain reaction was used to analyze the polymorphism at the APOE locus. The APOE allele frequencies were compared with those of a Greek control sample of 216 healthy blood donors. Patients with no cardiac impairment had an APOE 4 allele frequency (7.9%) not different from population controls (6.5%, P > .05), while patients with LVF had a significantly higher frequency of APOE 4 (12.8%) than the controls (P < .05, odds ratio = 2.11, 95% confidence interval 1.03 to 4.32). The APOE 4 allele may represent an important genetic risk factor for the development of organ damage in homozygous beta-thalassemia.     

Change in cognitive functioning associated with ApoE genotype in a community sample of older adults.

The influence of a genetic risk factor, apolipoprotein E (apoE) ε4 variant, was assessed in older adults aged 70 to 94 on 3 occasions over 7 years. The results of latent growth curve analyses are reported for individuals genotyped for apoE at the 2nd measurement occasion (n = 601) and for a subsample of individuals without probable or definite dementia during the 1st or 2nd occasion (n = 434). ApoE-ε4 status was a significant predictor of level and change in memory performance and change in speed performance in the full sample, and of initial level and change in memory performance in the nondemented subsample. These results support previous findings that apoE-ε4 is associated with accelerated memory deterioration in individuals without clinical dementia. (PsycINFO Database Record (c) 2010 APA, all rights reserved)