Obese very old women have low relative hangrip strength, poor physical function, and difficulties in daily living.

OBJECTIVES: To investigate whether anthropometric and body composition variables and handgrip strength (HS) were associated with physical function and independent daily living in 88-year-old Swedish women. PARTICIPANTS: A cross-sectional analysis of 83 community-dwelling women aged 88 years who were of normal weight (n=30), overweight (n=29), and obese (n=24) was performed. MEASUREMENTS: Body weight (Wt), height, waist circumference (WC), and arm circumference were assessed using an electronic scale and a measuring tape. Tricep skinfold thickness was measured using a skinfold calliper. Fat mass (FM) and fat-free mass (FFM) were measured using bioelectrical impedance analysis, and HS was recorded with an electronic grip force instrument. Linear regression was used to determine the contributions of parameters as a single predictor or as a ratio of HS to physical function (Short Form-36, SF-36PF) and instrumental activities of daily living (IADL). RESULTS: Obese women had greater absolute FM and FFM and lower HS corrected for FFM and HS-based ratios (i.e., HS/Wt, HS/body mass index [BMI]) than their normal weight and overweight counterparts. After adjusting for physical activity levels and the number of chronic diseases, HS-based ratios explained more variance in SF-36PF scoring (R2, 0.52-0.54) than single anthropometric and body composition variables (R2, 0.45-0.51). WC, HS, and HS-based ratios (HS/Wt and HS/FFM) were also associated with independence in IADL. CONCLUSION: Obese very old women have a high WC but their HS is relatively low in relation to their Wt and FFM. These parameters are better than BMI for predicting physical function and independent daily living.

Unaltered Image of Health Maintenance: An Observation of Non-Participants in a Swedish Cohort Study of 85 to 86 Year Olds.

BACKGROUND: Selection bias is often inevitable in epidemiologic studies. It is not surprising that study conclusions based on participants' health status are frequently questioned. OBJECTIVE: This study aimed to assess whether the non-participants affected the characteristics of a general population of the very old people. DESIGN, SETTING AND PARTICIPANTS: Prospective, cross-sectional (N=650, aged 85 years old) analysis and 1-year follow-up (n=273), in Linköping, Sweden. MEASUREMENTS: We analysed data on health-related factors from a postal questionnaire, a home visit and a clinic visit at baseline and at the 1-year follow-up. We calculated the effect size to evaluate the degree of differences between the groups. RESULTS: A greater proportion of non-participants resided in sheltered accommodation or nursing homes (participants vs non-response vs refusal, 11% vs 22% vs 40, P<0.001, φ=0.24). During the home visit or clinic visit, a higher proportion of dropouts reported mid-severe problems in EQ-5D domains (mobility and self-care) and limitations in personal activities of daily living, but the differences between participants and dropouts were very small (φ<0.2). No significant difference was found between the groups with regard to emergency room visits or hospital admissions, despite the fact that more participants than dropouts (φ=0.23) had multimorbidities (≥2 chronic diseases). Living in sheltered accommodation or a nursing home (odds ratio (OR), 2.8; 95% confidence interval (CI), 1.5-5), female gender (OR, 1.8; 95% CI, 1.1-3.1) and receiving more home visits in primary care (OR, 1.03; 95% CI, 1-1.06) contributed positively to drop out in the data collection stages over the study period. CONCLUSION: Non-participants were not considered to be a group with worse health. Mobility problems may influence very old people when considering further participation, which threatens attrition.

Hot flushes still occur in a population of 85-year-old Swedish women.

OBJECTIVES: Hot flushes and night sweats often cause discomfort and may negatively affect sleep and quality of life. Studies have shown that menopausal symptoms, like hot flushes, may persist for up to 20 years after the menopausal transition, but there are no published studies regarding the occurrence of hot flushes among women older than 80 years. The aim of this study is to determine the prevalence of hot flushes in 85-year-old women. METHODS: All 85-year old women living in Linköping municipality in 2007 (n = 415) received a postal questionnaire. The majority, 74% (n = 307), answered the questionnaire and 47% (n = 194) agreed to visit the Department of Geriatric Medicine; during this visit questions regarding hot flushes and use of hormone therapy were asked. RESULTS: About 16% (n = 29) of the women experienced hot flushes during the day and/or during the night and 6.5% (n = 12) of the women were currently using hormone therapy. Almost 10% (n = 17) of all responding women were very to moderately distressed by their hot flushes. CONCLUSION: Our results confirm and extend previous knowledge based on studies of younger postmenopausal women in showing that menopausal symptoms still occur in elderly women. We found that, while the prevalence of menopausal symptoms decreases with age, these symptoms are still experienced by some 85-year-old women.

Age and diagnostic performance of Alzheimer disease CSF biomarkers.

OBJECTIVES: Core CSF changes in Alzheimer disease (AD) are decreased amyloid ß(1-42), increased total tau, and increased phospho-tau, probably indicating amyloid plaque accumulation, axonal degeneration, and tangle pathology, respectively. These biomarkers identify AD already at the predementia stage, but their diagnostic performance might be affected by age-dependent increase of AD-type brain pathology in cognitively unaffected elderly. METHODS: We investigated effects of age on the diagnostic performance of CSF biomarkers in a uniquely large multicenter study population, including a cross-sectional cohort of 529 patients with AD dementia (median age 71, range 43-89 years) and 304 controls (67, 44-91 years), and a longitudinal cohort of 750 subjects without dementia with mild cognitive impairment (69, 43-89 years) followed for at least 2 years, or until dementia diagnosis. RESULTS: The specificities for subjects without AD and the areas under the receiver operating characteristics curves decreased with age. However, the positive predictive value for a combination of biomarkers remained stable, while the negative predictive value decreased only slightly in old subjects, as an effect of the high AD prevalence in older ages. CONCLUSION: Although the diagnostic accuracies for AD decreased with age, the predictive values for a combination of biomarkers remained essentially stable. The findings highlight biomarker variability across ages, but support the use of CSF biomarkers for AD even in older populations.

In vitro screening for putative psoriasis-specific antigens among wheat proteins and peptides.

BACKGROUND: Patients with psoriasis who had raised IgG and/or IgA antigliadin antibodies showed clinical improvement in a trial with a gluten-free diet. The selection of patients for the diet treatment was based on the presence of specific antibodies, i.e. the result of humoral immunity. OBJECTIVES: As psoriasis is now considered to be a T cell-mediated disease we decided to challenge peripheral blood mononuclear cells (PBMCs) in vitro from randomly selected patients with well-defined wheat proteins/peptides to explore the possibility of identifying a specific antigen with T cell activating properties in a subgroup of patients. METHODS: PBMCs from 37 patients (20 female and 17 male; mean age 49years) and 37 healthy controls (12 female and 25 male; mean age 57years) were included. Not all patients participated in all experiments. The PBMCs were exposed in vitro with the following wheat proteins/peptides in various concentrations: total albumins, 0·28 α-amylase inhibitor and the synthetic peptides, p31-43, p57-68 and p62-75, based on coeliac-active sequences of α-gliadin. The proliferative response was measured as counts per minute after the cells had been pulsed with methyl-(3) H-thymidine. RESULTS: Albumin, α-amylase inhibitor, p31-43 and p57-68 elicited a significant response in both patients and controls but showed no differences between the groups. The response induced by the α-amylase inhibitor was higher than that induced by the albumin fraction and the p31-43 and p57-68 peptides. At a concentration of 25µgmL(-1) , five of 36 patients with psoriasis responded positively to the p62-75 peptide and none of the 33 controls, using a stimulation index of 2·4 as the cut-off level (P<0·05). These five patients did not show clinical features that differed from the remaining patients. Among the responding patients the relative number of CD4+ cells increased in some but not all after in vitro challenge with the albumins, 0·28 α-amylase inhibitor, and p62-75. These antigens could also induce in vitro the expression of the homing antigen cutaneous lymphocyte antigen (CLA) in a few patients and controls. CONCLUSIONS: The wheat protein antigens, especially the p62-75 peptide, might be of interest in a subgroup of patients with psoriasis.

Hearing difficulties, uptake, and outcomes of hearing aids in people 85 years of age.

OBJECTIVE: The aim of this study was to investigate self-reported hearing difficulties, uptake, and hearing-aid outcomes and their relationships to demographic, cognitive, psychosocial, and health variables in 85 year olds. DESIGN AND STUDY SAMPLE: Three hundred and forty-six elderly adults participated in a survey that included questionnaires and home visits. Fifty-five percent of participants admitted to having hearing difficulties, and 59% of these owned hearing aids. The participants' most frequently cited reason for not acquiring hearing aids was that they did not think their hearing problem was perceived as severe enough. Participants with hearing difficulties who did not own hearing aids showed worse general and mental health. Many of the elderly participants were successful in their rehabilitation, and their hearing-aid outcomes were similar to those of a younger group, with the exception of a greater proportion of non-users among the elderly. CONCLUSION: Many older people with self-reported hearing difficulties do not acquire hearing aids, despite this study's findings that older people are likely to have success with hearing rehabilitation. It is important to make greater efforts to try to increase elderly adults' awareness of hearing loss and the benefits of hearing rehabilitation.

Association of insulin-like growth factor-1 receptor polymorphism in dementia.

There is an increasing interest in how oxidative stress can cause cells to go into apoptosis in both normal ageing and in neurodegenerative disorders. Previous research has implicated insulin-like growth factor-1 (IGF-1) as being involved in the pathogenesis in Alzheimer's disease (AD) by protecting the neurons through reducing neuronal susceptibility to oxidative stress. IGF-1 receptor (IGF-1R) polymorphisms alter cerebral and systemic levels of IGF-1 and may alter the function of the receptor. We genotyped the IGF-1R gene by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) to assess whether this gene polymorphism can be linked to dementia. We used leukocyte DNA from 72 patients with AD, 75 patients with vascular dementia (VaD), 14 patients with mixed dementia (AD+VaD), and a control group consisting of 209 individuals without a history of progressive neurological disorders. Analysis of gene frequency for gender revealed a significant difference between female VaD patients and female controls carrying at least one A allele (OR = 1.8, CI 95% 1.1-2.9, p = 0.02), but not for male patients. In addition, we found a strong tendency to a difference between all cases of female dementia patients and controls carrying the A allele (OR = 1.5, CI 95% 0.99-2.2, p = 0.054). Our results suggest that the A allele of IGF-1R may be involved in the pathogenesis of VaD in females.

APOE epsilon4 allele is associated with reduced cerebrospinal fluid levels of Abeta42.

The epsilon4 allele of APOE is a risk factor for Alzheimer disease (AD). By analysis of a large cohort of AD patients (n = 563) and control subjects (n = 118), it is shown that the epsilon4 allele is strongly associated with reduced CSF levels of beta-amyloid (1-42) (Abeta42) in both AD (p < 10(-9)) and control (p = 0.0012) populations. As no associations of APOE variants with other indexes of AD severity were observed, this effect may reflect a fundamental involvement of ApoE in Abeta metabolism.

Cobalamin, folate, methylmalonic acid, homocysteine, and gastritis markers in dementia.

The prevalence of dementia disorders, cobalamin and/or folate deficiency as well as gastritis increases with age. To investigate whether there is an association between these conditions, plasma homocysteine (Hcy), serum methylmalonic acid, serum cobalamin and blood folate concentrations were measured. Gastritis was indirectly diagnosed by measuring serum antibodies against H,K-ATPase, HELICOBACTER PYLORI and intrinsic factor, using enzyme-linked immunosorbent assays. The studied groups consisted of 47 patients with Alzheimer's disease (AD), 9 with AD pathology in combination with additive vascular lesions, 59 with vascular dementia, 8 who were cognitively impaired, and 101 control cases. Plasma Hcy concentrations were significantly elevated in the dementia groups, with the highest levels in patients with vascular pathology. We conclude that hyperhomocysteinemia is a common finding in patients with dementia disorders of different etiologies. The markers for gastritis did not contribute to an elucidation of a possible connection between this condition, dementia disorders, or cobalamin/folate deficiency.

Dementia in primary care: why the low detection rate?

OBJECTIVE: The aim of the present study was to find reasons for the low detection rate of dementia in primary care. Another aim was to investigate the attitudes and knowledge on dementia among Swedish general practitioners (GPs). DESIGN: Two-hundred-and-twenty-eight postal questionnaires were distributed to GPs in the county of Ostergötland. SETTING: Primary care in Sweden. MAIN OUTCOME MEASURES: The opinions of GPs on dementia management in primary care. RESULTS: The response rate was 67%. GPs showed a good knowledge of dementia diseases but underestimated the occurrence of dementia. They presented a positive attitude towards managing patients with dementia and considered that existing drug therapy justified an active search for patients with dementia in primary care, but they believed the efficacy of the drugs to be limited. Assessing the social environment of patients and organising social support were regarded as the most difficult tasks in the management of demented patients. CONCLUSION: The study indicates that the main obstacles are a lack of resources and a sceptical attitude to the benefits of drug treatment. Co-operation between the community services, specialist clinics and the primary care team should be improved.

Tau and Abeta42 in cerebrospinal fluid from healthy adults 21-93 years of age: establishment of reference values.

BACKGROUND: Tau protein and the 42-amino acid form of beta-amyloid (Abeta42) measured in cerebrospinal fluid (CSF) have been proposed as potential biochemical diagnostic markers for Alzheimer disease. For the introduction of these assays in clinical practice, adequate reference values are of importance. METHODS: CSF samples were obtained from 231 neurologically and psychiatrically healthy individuals, 21-93 years of age, all with a MiniMental State examination score of 28 or above. Standardized ELISAs were used to measure tau and Abeta42 in CSF. Following IFCC recommendations, we used a rank-based method; the 0.90 and 0.10 fractiles were estimated to establish reference values for CSF-tau and CSF-Abeta42, respectively. Putative confounding factors, such as the influence of the passage of proteins from peripheral blood to CSF, influence of dysfunction of the blood-brain barrier, and freezing and thawing of CSF, were investigated. RESULTS: A correlation with age was found for CSF-tau (r = 0.60; P <0.001). Therefore, separate reference values for different age groups were established for CSF-tau: <300 ng/L in the group 21-50 years of age, <450 ng/L in the group 51-70 years of age, and <500 ng/L in the group 71-93 years of age. CSF-Abeta42 did not correlate with age (r = -0.045), and the reference value was set to >500 ng/L. No correlation was found between blood-brain barrier function and CSF-tau or CSF-Abeta42. CONCLUSIONS: These reference values can be applied when using CSF-tau and CSF-Abeta42 in clinical practice.

[Harmonization of dementia diagnoses--a necessary quality assurance]. / Harmonisering av demensdiagnoser--en nödvändig kvalitetssäkring.

Classification and registration of diseases is necessary in order to monitor the proliferation of diseases in a population. Despite the presence of an international framework for classification of diseases (ICD 10) which has been approved by the Swedish authorities, the guidelines provided are not observed in the area of dementia diseases. Different diagnoses can be used to describe the same condition, and "dementia unspecified" is sometimes employed when a specified diagnosis could have been used. In order to refine consensus regarding the use of different diagnoses in the dementia field, representatives for the Swedish University hospitals and medical faculties propose a unified description of a limited number of dementia diagnoses.

Tacrine and rate of progression in Alzheimer's disease--relation to ApoE allele genotype.

Today, cognitive impairment can be successfully treated with acetylcholine esterase inhibitors (AChE-I) in many, but not all, patients with Alzheimer's disease (AD). To investigate the relation between tacrine treatment, inheritance of ApoE epsilon4 alleles, and rate of progression, the differences in MMSE and CIBIC scores (efficacy parameters) after 6 and 12 months of tacrine (an AChE-I) treatment were investigated in 145 AD patients. Of these, 84 were ApoE epsilon4-positive (ApoE4) and 61 were ApoE epsilon4-negative (ApoE2-3). No differences were found after 6 months of treatment, but after 12 months the CIBIC scores revealed that the ApoE4 patients had declined more than the ApoE2-3 patients (p < 0.05). No differences were found for the last 6 months of treatment. The results primarily suggest a faster rate of decline in the ApoE4 AD compared to the ApoE2-3, but may also reflect that ApoE epsilon4 genotype inheritance is a negative predictor of treatment effect of tacrine in AD patients.

Mental disorders among elderly people in primary care: the Linköping study.

OBJECTIVE: The aims of this study were to describe the prevalence of mental disorders among elderly patients in primary care and to compare diagnoses from psychiatric interview with diagnoses in medical records. METHOD: Patients aged 70 years and above attending a primary care centre (N = 350) were studied using a psychiatric and medical record examination. RESULTS: The prevalence of mental disorder according to the psychiatric interview was 33% (16% dementia, 17% other mental disorders). Only 49% of these had any psychiatric diagnosis in case records and 17-38% received specific treatments. The frequency of psychiatric symptoms among those with no mental disorder was between 1% and 66%. Patients with mental disorders were more often females, had more visits to a doctor, more diagnoses in medical records, and were prescribed more drugs. CONCLUSION: Mental disorders and symptoms are common among the elderly in primary care. More effort should be made to increase the recognition rate.

Protective effects of tanning on cutaneous DNA damage in situ.

BACKGROUND: The incidence of skin cancer, the most common type of cancer in the Western world, has been shown to be associated with the degree of exposure to solar radiation. However, little is known on how human skin can be protected against UV-induced DNA damage by constitutive and induced pigmentation. OBJECTIVE: To study the effect of skin pigmentation induced by a sunbed-type of treatment on the formation of UV-induced DNA damage in human skin in situ. METHODS: A photoproduct assay was performed in untanned and tanned skin of healthy volunteers. RESULTS: There is no significant difference in the induction of photoproducts between untanned and tanned skin. CONCLUSION: Our data demonstrate that constitutive skin pigmentation is more efficient than the induced one in protection against formation of photoproducts.

Mercury intolerance and lymphocyte transformation test with nickel sulfate, palladium chloride, mercuric chloride, and gold sodium thiosulfate.

The peripheral lymphocytes of 10 patients referred to as mercury intolerant and 9 patients referred to as tolerant with regard to presence or absence of psychosomatic symptoms when percutaneously exposed to low patch test doses of mercury were stimulated in vitro with four metal salts. In addition, cells from 7 subjects with no anamnestic mercury intolerance or allergy to metals as well as free from dental alloys were included as controls. Lymphocyte transformation test was done by in vitro challenge with five concentrations of gold sodium thiosulfate, nickel chloride, palladium chloride, and seven concentrations of mercuric chloride. Stimulation with palladium chloride and mercuric chloride showed a difference between the mercury-intolerant and -tolerant patients on one hand and the controls on the other, but there was no difference between the two patient groups. With regard to nickel sulfate, there was a significant dose-dependent stimulation in all the three groups but no difference between the groups could be seen. Gold sodium thiosulfate did not stimulate the lymphocytes at all. Based on these results, we therefore conclude that lymphocyte transformation test performed with the four metal salts cannot be used to further differentiate between mercury-intolerant and -tolerant patients.

No association between the alpha2-macroglobulin (A2M) deletion and Alzheimer's disease, and no change in A2M mRNA, protein, or protein expression.

A polymorphism consisting of a deletion near the 5' splice site of exon 18 on the alpha2-macroglobulin (A2M) gene (A2M-2) has been suggested to be associated with Alzheimer's disease (AD) in family-based studies. We studied the A2M-2 allele together with the ApoE alleles in a large series on patients with AD (n = 449) and age-matched controls (n = 349). Neuropathologically confirmed diagnoses were available in 199 cases (94 AD and 107 control cases). We found no increase in A2M-2 genotype or allele frequencies in AD (27.5% and 14.6%) versus controls (26.4% and 14.9%). In contrast, a marked increase (p < 0.0001) in ApoE epsilon4 genotype or allele frequencies was found in AD (66.6% and 41.2%) as compared with controls (29.8% and 16.5%), suggesting sufficient statistical power in our sample. No relation was found between the A2M-2 and the ApoE epsilon4 allele. No change in A2M exon 17-18 mRNA size or sequence or A2M protein size was found in cases carrying the A2M-2 deletion, suggesting that there is no biological consequences of the A2M intronic deletion. No change in A2M protein level in cerebrospinal fluid was found in AD, suggesting that the A2M-2 allele does not effect the A2M protein expression in the brain. The lack of an association between the A2M-2 allele and AD in the present study, and the lack of abnormalities in the A2M mRNA or protein suggest that the A2M-2 allele is not associated with AD.

Eosinophil cationic protein- and eosinophil-derived neurotoxin/eosinophil protein X-immunoreactive eosinophils in prurigo nodularis.

It is known that eosinophils are actively involved in allergy and inflammation. The granular components of eosinophils, eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin/eosinophil protein X (EDN/EPX), play an important role in such allergic and inflammatory processes. Prurigo nodularis is a chronic inflammatory skin disease with obvious cutaneous nervous involvement. To detect ECP and EDN/ EPX expression in the eosinophils and their relation to nerve fibres in prurigo nodularis, ECP and EDN/EPX single-labelling immunofluorescence, and ECP and PGP 9.5 double-labelling immunofluorescence, were performed. In prurigo nodularis lesional skin, the ECP- and EDN/EPX-containing cells, which were mainly distributed in the upper dermis, were significantly increased in number compared to their numbers in uninvolved and normal skin. The immunoreactivity of ECP and EDN/EPX in prurigo lesional skin was stronger than in uninvolved skin or control skin. The PGP 9.5-immunoreactive nerves were also increased in number in the areas where there were increased eosinophils. The nerves were in close proximity to eosinophils, and occasionally even seemed to be in contact. The present results indicate that the cutaneous nerves and the ECP- and EDN/EPX-containing eosinophils are possibly involved in the pathogenesis of the disease. The close relationship of nerves and eosinophils indicates that the cutaneous nerves may influence eosinophil function in the chronic inflammatory states of prurigo nodularis. ECP and EDN/EPX could thus be released to the local tissue and modulate the inflammation of the prurigo nodularis lesion.

Selective effects on NGFI-A, MR, GR and NGFI-B hippocampal mRNA expression after chronic treatment with different subclasses of antidepressants in the rat.

There is a latency period of several weeks before the onset of clinical effect of antidepressant drugs. The detailed mechanisms underlying drug-induced adaptive neuronal changes are not known. To elucidate the involvement of changes in gene expression of candidate transcription factors, we treated rats for 21 days with buspirone, fluoxetine, 8-OH-DPAT and moclobemide. In situ hybridization was used to study mRNAs encoding NGFI-A, NGFI-B and the glucocorticoid receptors, MR and GR. NGFI-A mRNA expression increased profoundly in the hippocampal formation and the cerebral cortex after all drug treatments, especially after moclobemide treatment (77-122% increase); with the exception of buspirone. MR mRNA expression was induced in hippocampal CA1/CA2 subregions (27-37%) by all antidepressants, while moclobemide and 8-OH-DPAT significantly increased GR gene expression mainly in the CA1 region (31-44%). NGFI-B mRNA was significantly decreased in the hippocampal CA3 subfield (23%) and restrosplenial granular cortex (38%) by moclobemide treatment. There are selective effects of antidepressant drugs on specific transcription factors. These may be important for adaptive neuronal and neuroendocrine changes after antidepressant treatment including HPA axis negative feedback regulation.