Influence of design of dentist's chairs on body posture for dentists with different working experience.

BACKGROUND: Musculoskeletal disorders (MSD) are a common health problem among dentists. Dental treatment is mainly performed in a sitting position. The aim of the study was to quantify the effect of different ergonomic chairs on the sitting position. In addition, it was tested if the sitting position of experienced workers is different from a non-dental group. METHODS: A total of 59 (28 m/31f) subjects, divided into two dentist groups according to their work experience (students and dentists (9 m/11f) < 10 years, dentists (9 m/10f) ≥ 10 years) and a control group (10 m/10f) were measured. A three-dimensional back scanner captured the bare back of all subjects sitting on six dentist's chairs of different design. Initially, inter-group comparisons per chair, firstly in the habitual and secondly in the working postures, were carried out. Furthermore, inter-chair comparison was conducted for the habitual as well as for the working postures of all subjects and for each group. Finally, a comparison between the habitual sitting posture and the working posture for each respective chair (intra-chair comparison) was conducted (for all subjects and for each group). In addition, a subjective assessment of each chair was made. For the statistical analysis, non-parametric tests were conducted and the level of significance was set at 5%. RESULTS: When comparing the three subject groups, all chairs caused a more pronounced spinal kyphosis in experienced dentists. In both conditions (habitual and working postures), a symmetrical sitting position was assumed on each chair. The inter-chair comparisons showed no differences regarding the ergonomic design of the chairs. The significances found in the inter-chair comparisons were all within the measurementerror and could, therefore, be classified as clinically irrelevant. The intra-chair comparison (habitual sitting position vs. working sitting position) illustrated position-related changes in the sagittal, but not in the transverse, plane. These changes were only position-related (forward leaned working posture) and were not influenced by the ergonomic sitting design of the respective chair. There are no differences between the groups in the subjective assessment of each chair. CONCLUSIONS: Regardless of the group or the dental experience, the ergonomic design of the dentist's chair had only a marginal influence on the upper body posture in both the habitual and working sitting postures. Consequently, the focus of the dentist's chair, in order to minimize MSD, should concentrate on adopting a symmetrical sitting posture rather than on its ergonomic design.

Theoretical exploration of the neural bases of behavioural disinhibition, apathy and executive dysfunction in preclinical Alzheimer's disease in people with Down's syndrome: potential involvement of multiple frontal-subcortical neuronal circuits.

BACKGROUND: Recent research has suggested a specific impairment in frontal-lobe functioning in the preclinical stages of Alzheimer's disease (AD) in people with Down's syndrome (DS), characterised by prominent changes in personality or behaviour. The aim of the current paper is to explore whether particular kinds of change (namely executive dysfunction (EDF), disinhibition and apathy), associated in the literature with disruption of different underlying frontal-subcortical circuits, are a) more or less frequently reported than others and b) related to poor performance on tasks involving different cognitive processes. METHOD: Seventy-eight participants (mean age 47 years, range 36-72) with DS and mild to moderate intellectual disability (based on ICD-10 criteria), without a diagnosis of dementia of Alzheimer's type (DAT) or other psychiatric disorders, were selected from a larger sample of older adults with DS (n = 122). Dementia diagnosis was based on the CAMDEX informant interview, conducted with each participant's main carer. Informant-reported changes in personality/behaviour and memory were recorded. Participants were scored based on symptoms falling into three behavioural domains and completed five executive function (EF) tasks, six memory tasks (two of which also had a strong executive component) and the BPVS (as a measure of general intellectual ability). Multiple regression analyses were conducted to determine the degree to which the behavioural variables of 'EDF', 'disinhibition' and 'apathy', along with informant-reported memory decline and antidepressant medication use, predicted performance on the cognitive tasks (whilst controlling for the effects of age and general intellectual ability). RESULTS: Strikingly, disinhibited behaviour was reported for 95.7% of participants with one or more behavioural change (n = 47) compared to 57.4% with reported apathy and 36.2% with reported EDF. 'Disinhibition' score significantly predicted performance on three EF tasks (designed to measure planning, response inhibition and working memory) and an object memory task, (also thought to place high demands on working memory), while 'apathy' score significantly predicted performance on two different tasks, those measuring spatial reversal and prospective memory (p < 0.05). Informant reported memory decline was associated only with performance on a delayed recall task while antidepressant medication use was associated with better performance on a working memory task (p < 0.05). CONCLUSION: Observed dissociation between performance on cognitive tasks associated with reported apathy and disinhibition is in keeping with proposed differences underlying neural circuitry and supports the involvement of multiple frontal-subcortical circuits in the early stages of DAT in DS. However, the prominence of disinhibition in the behavioural profile (which more closely resembles that of disinhibited subtype of DFT than that of AD in the general population) leads us to postulate that the serotonergically mediated orbitofrontal circuit may be disproportionately affected. A speculative theory is developed regarding the biological basis for observed changes and discussion is focused on how this understanding may aid us in the development of treatments directly targeting underlying abnormalities.

Parental practices predict psychological well-being in midlife: life-course associations among women in the 1946 British birth cohort.

BACKGROUND: Certain parenting styles are influential in the emergence of later mental health problems, but less is known about the relationship between parenting style and later psychological well-being. Our aim was to examine the association between well-being in midlife and parental behaviour during childhood and adolescence, and the role of personality as a possible mediator of this relationship. METHOD: Data from 984 women in the 1946 British birth cohort study were analysed using structural equation modelling. Psychological well-being was assessed at age 52 years using Ryff's scales of psychological well-being. Parenting practices were recollected at age 43 years using the Parental Bonding Instrument. Extraversion and neuroticism were assessed at age 26 years using the Maudsley Personality Inventory. RESULTS: In this sample, three parenting style factors were identified: care; non-engagement; control. Higher levels of parental care were associated with higher psychological well-being, while higher parental non-engagement or control were associated with lower levels of psychological well-being. The effects of care and non-engagement were largely mediated by the offspring's personality, whereas control had direct effects on psychological well-being. The psychological well-being of adult women was at least as strongly linked to the parenting style of their fathers as to that of their mothers, particularly in relation to the adverse effects of non-engagement and control. CONCLUSIONS: This study used a prospective longitudinal design to examine the effects of parenting practices on psychological well-being in midlife. The effects of parenting, both positive and negative, persisted well into mid-adulthood.

Prevalence of depressive symptoms and syndromes in later life in ten European countries: the SHARE study.

BACKGROUND: The EURO-D, a12-item self-report questionnaire for depression, was developed with the aim of facilitating cross-cultural research into late-life depression in Europe. AIMS: To describe the national variation in depression symptoms and syndrome prevalence across ten European countries. METHOD: The EURO-D was administered to cross-sectional nationally representative samples of non-institutionalised persons aged > or =50 years (n=22 777). The effects of age, gender, education and cognitive functioning on individual symptoms and EURO-D factor scores were estimated. Country-specific depression prevalence rates and mean factor scores were re-estimated, adjusted for these compositional effects. RESULTS: The prevalence of all symptoms was higher in the Latin ethno-lingual group of countries, especially symptoms related to motivation. Women scored higher on affective suffering; older people and those with impaired verbal fluency scored higher on motivation. CONCLUSIONS: The prevalence of individual EURO-D symptoms and of probable depression (cut-off score > or =4) varied consistently between countries. Standardising for effects of age, gender, education and cognitive function suggested that these compositional factors did not account for the observed variation.

WITHDRAWN: Dehydroepiandrosterone (DHEA) supplementation for cognitive function.

BACKGROUND: In view of the theoretical rationale for beneficial effects of DHEA and DHEAS on cognitive function in ageing and dementia, we have undertaken a thorough investigation of well-conducted studies in this area. This will provide a basis for confirmation of any effect of DHEA/S administration in humans in properly controlled trials. The review will also provide a scientific basis for effective dosage, acceptable route and duration of administration, and side effect profiles. This review is especially pertinent at this time as DHEA is currently being sold in large quantities in health food stores, particularly in the USA. In some cases the recommended dose is different for men and women (50mg/day for men and 25mg/day for women) and the basis for this recommendation needs to be explored. OBJECTIVES: To establish whether administration of DHEA, or its sulphate, DHEAS, improves cognitive function or reduces the rate of decline of cognitive function in normal older adults or in individuals with dementia. SEARCH STRATEGY: Relevant electronic databases, journals, personal communications and conference abstracts were searched for randomised controlled trials investigating the effects of DHEA/S on cognition in older adults. SELECTION CRITERIA: All relevant randomised controlled trials of DHEA/S were considered for inclusion in the review. DATA COLLECTION AND ANALYSIS: Data for the specified outcomes were independently extracted by two reviewers (FAH & JvN) and cross-checked. Any discrepancies were discussed and resolved. No data pooling was undertaken owing to the lack of availability of the relevant statistics. MAIN RESULTS: There are four included studies, three cognition in normal older people, and Barnhart 1999 in perimenopausal women with decreased well-being. There were no studies in dementia. There were a few significant findings. Wolf 1997 found significant improvement following DHEA compared with placebo in both immediate recall (MD 0.8, 95% CI 0.16, 1.44) and delayed recall (MD 0.9, 95% CI 0.09, 1.71) of a visual memory test in women, estimated in a crossover trial after 2 weeks of treatment with each of DHEA and placebo. However there was no significant improvement in men, nor a significant effect on a verbal memory test. There was also no significant effect on four other cognitive tests. Wolf 1998 (2) found that placebo group performance deteriorated significantly on a test of selective attention following a psychosocial stressor (p<0.05), while deterioration was not evident in the DHEA group (p=0.85) after two weeks of treatment. However, when compared to placebo, DHEA produced a significant impairment on a visual memory test (p<0.01) following the stressor. No significant effect was found on a third cognitive task. Effects were not found on tasks when administered in the absence of a stressor. Barnhart 1999 employed three cognitive measures and found no significant effect of DHEA compared with placebo at 3 months. Findings to date suggest that DHEA replacement seems to be well tolerated with an absence of significant side-effects. AUTHORS' CONCLUSIONS: The data offer no support at present for an improvement in memory or other aspects of cognitive function following DHEA treatment in normal older people. In view of the growing public enthusiasm for DHEA supplementation, particularly in the USA, and the possibility that any neuroprotective effect of DHEA/S may only be evident in the long term, there is a need to undertake high quality trials in which the duration of DHEA treatment is longer than one year, and the number of participants is large enough to detect effects if they exist.Recently, trials of DHEA supplementation in Alzheimer's Disease (USA), post-menopausal women (USA), normal older men (UK), and a one-year trial in normal older men and women (France) have been completed. As soon as the results are available these studies will be included in the review.

Was John Reid right? Smoking, class, and pleasure: a population-based cohort study in England.

OBJECTIVES: To assess whether there is a relationship between smoking and levels of overall quality of life, or with the pleasure domain of quality of life, in lower socio-economic groups (SES). STUDY DESIGN: Cohort study involving 9176 individuals aged 50 years and over who participated in the Health Survey for England and were followed up in Wave 1 of the English Longitudinal Study of Ageing in 2002. METHODS: We classified smokers as never-smokers, ex-smokers and current smokers, and used household wealth as a marker for socio-economic position. Pleasure was assessed using the pleasure subscale of the CASP-19 instrument, a 19-point measure of quality of life that covers four theoretical domains: control, autonomy, self-realization and pleasure. RESULTS: We found that the odds ratio for experiencing lower than median levels of pleasure for smokers with low SES was 1.42 (95% CI 1.16-1.74), and for all smokers was 1.33 (95% CI 1.17-1.51). The same pattern of associations was found when the outcome was total CASP-19 score or positive GHQ-12 score. CONCLUSIONS: We found no evidence to support a claim that smoking is associated with heightened levels of pleasure, either in people with low SES or in the general population. In fact, our results suggest the opposite: that smoking is associated with lower levels of pleasure and poorer overall quality of life. Policy decisions on smoking should consider its potentially harmful effect on quality of life and pleasure as well as on other aspects of health.

Dehydroepiandrosterone (DHEA) supplementation for cognitive function in healthy elderly people.

BACKGROUND: In view of the theoretical possibility of beneficial effects of DHEA or DHEAS in retarding age-associated deterioration in cognitive function, we have reviewed studies in this area. OBJECTIVES: To establish whether administration of DHEA, or its sulphate, DHEAS, improves cognitive function or reduces the rate of decline of cognitive function in normal older adults. SEARCH STRATEGY: Trials were identified from a last updated search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 10 October 2005 using the terms dhea*, prasterone, dehydroepiandrosterone*. In addition MEDLINE, EMBASE, PsycINFO and CINAHL were searched to find trials with volunteers who had no or minor memory complaints. Relevant journals, personal communications and conference abstracts were searched for randomized controlled trials investigating the effects of DHEA/S on cognition in older adults. SELECTION CRITERIA: All randomized placebo-controlled trials enrolling people aged over 50 without dementia and to whom DHEA/S in any dosage was administered for more than one day were considered for inclusion in the review. DATA COLLECTION AND ANALYSIS: Data for the specified outcomes were independently extracted by two reviewers (JGE and RM) and cross-checked. Any discrepancies were discussed and resolved. No data pooling was undertaken owing to the lack of availability of the relevant statistics. MAIN RESULTS: Only three studies provided results from adequate parallel-group data. Barnhart 1999 enrolled perimenopausal women with complaints of decreased well-being and, using three cognitive measures, found no significant effect of DHEA compared with placebo at 3 months. Wolf 1998b enrolled 75 healthy volunteers (37 women and 38 men aged 59-81) in a study of the effect of DHEA supplements on cognitive impairment induced by stress; after two weeks of treatment, placebo group performance deteriorated significantly on a test of selective attention following a psychosocial stressor (p<0.05), while deterioration was not evident in the DHEA group (p=0.85). However, when compared with placebo, DHEA was associated with a significant impairment on a visual memory recall test (p<0.01) following the stressor. No significant effects were found on a third cognitive task. Effects were not found on tasks when administered in the absence of a stressor. van Niekerk 2001 found no effect on cognitive function in 46 men aged 62-76 from three months of DHEA supplementation. DHEA supplements were well tolerated and without significant adverse effects apart from the reduced performance in the visual memory recall test observed in one trial. AUTHORS' CONCLUSIONS: What little evidence there is from controlled trials does not support a beneficial effect of DHEA supplementation on cognitive function of non demented middle-aged or elderly people. There is no consistent evidence from the controlled trials that DHEA produces any adverse effects. In view of growing public enthusiasm for DHEA supplementation, particularly in the USA, and the theoretical possibility of long-term neuroprotective effects of DHEA/S, there is a need for further high quality trials in which the duration of DHEA treatment is longer than one year, and the number of participants is large enough to provide adequate statistical power.

The modified CAMDEX informant interview is a valid and reliable tool for use in the diagnosis of dementia in adults with Down's syndrome.

BACKGROUND: Dementia because of Alzheimer's disease (AD) commonly affects older adults with Down's syndrome (DS). Methods are needed, with established concurrent and predictive validity, to facilitate the diagnostic assessment of dementia, when it is complicated by pre-existing intellectual disabilities (ID). We report on the reliability and validity of a modified version of the Cambridge Examination for Mental Disorders of the Elderly (CAMDEX) informant interview, for use when assessing people with DS suspected as having dementia. METHODS: As part of a previous epidemiological study of older people with DS, the CAMDEX informant interview was used to determine the prevalence of dementia. The 74 people with DS included at that time (Time 1) had also completed the Cambridge Cognitive Examination (CAMCOG), the neuropsychological assessment from the CAMDEX schedule. Fifty-six were assessed again 6 years later (Time 2). Based on the CAMDEX informant interview, nine of the 74 at Time 1, and 11 of the 56 at Time 2, were found to meet clinical criteria for AD. Forty-one scored above floor on the CAMCOG at Time 1 and were included in the analysis of cognitive decline. Concurrent validity was established by comparing diagnosis at Time 2 with independent evidence of objective decline on cognitive tasks since Time 1. Predictive validity was established by examining how accurately diagnosis at Time 1 predicted both cognitive decline and future diagnosis. Inter-rater reliability was determined by comparing the level of agreement between two raters. RESULTS: CAMDEX-based diagnosis of AD was shown to be consistent with objectively observed cognitive decline (good concurrent validity) and to be a good predictor of future diagnosis. Although numbers are small, some support is also provided for the accuracy with which diagnosis predicts cognitive decline. Inter-rater reliability was good with Kappa > 0.8 for 91% of items and > 0.6 for all items. CONCLUSIONS: The use of the modified CAMDEX informant interview enables the structured collection of diagnostic information, so that a valid and a reliable diagnosis of dementia can be made in those with pre-existing ID, using established diagnostic criteria.

Hormone replacement therapy for cognitive function in postmenopausal women.

BACKGROUND: As estrogens have been found in animal models to be associated with the maintenance and protection of brain structures, it is biologically plausible that maintaining high levels of estrogens in postmenopausal women by medication could be protective against cognitive decline. OBJECTIVES: To investigate the effect of ERT (estrogens only) or HRT (estrogens combined with a progestagen) in comparison with placebo in randomized controlled trials (RCTs) on cognitive function in postmenopausal women. SEARCH STRATEGY: The CDCIG Specialized Register was searched using the terms ORT, PORT, ERT, HRT, estrogen*, oestrogen*, progesteron* on 16 May 2002. In addition MEDLINE (1966-2002/01); EMBASE (1985-2000/11); PsycINFO (1967-2002/01) and CINAHL (1982-2001/12) were searched as the CDCIG Register does not contain all trials with healthy volunteers. SELECTION CRITERIA: All double-blind randomized controlled trials of the effect of ERT or HRT on cognitive function over a treatment period of at least two weeks in postmenopausal women. DATA COLLECTION AND ANALYSIS: Abstracts of the references retrieved by the searches were read by two reviewers in order to discard those that were clearly not eligible for inclusion. The two reviewers studied the full text of the remaining references and independently selected studies for inclusion. Any disparity in the resulting lists was resolved by discussion with all reviewers in order to arrive at the final list of included studies. The selection criteria ensured that the blinding and randomization of the included studies was adequate. Two reviewers (EH and KY) assessed the quality of other aspects including design and assessment of outcomes. One reviewer (EH) extracted the data from the studies. MAIN RESULTS: In total, 15 trials involving 566 postmenopausal women were included, but 6 studies did not have adequate data for analysis. Meta-analyses showed a positive effect of 10 mg of estradiol (E2) bolus injections intramuscularly monthly in relatively young surgically menopausal women on the Paired Associate learning test immediate recall (z=2.40, p<0.05, chi-square test=1.12, p=0.29, SMD=1.02, 95% C.I.=0.19-1.85), on a test of abstract reasoning (z=10.45, p<0.0001, WMD=6.80, 95% C.I.=5.52-8.08) and a test of speed and accuracy (z=9.16, p<0.0001 WMD=6.00, 95% C.I.=4.72-7.28). However, most studies showed no evidence of an effect on verbal or visuospatial memory, mental rotations, speed or accuracy measures. There was little evidence that Premarin, the most widely prescribed estrogen for postmenopausal use, had positive effects on cognitive function. The one effect of 9 months of treatment with Premarin (and a progestagen) on a measure of complex speed of information processing (the TMT-B) was probably explained by baseline differences, as it was not reported by the authors. REVIEWER'S CONCLUSIONS: There was little evidence regarding the effect HRT or ERT on overall cognitive function in healthy postmenopausal women. There was an effect on some verbal memory functions (immediate recall), on a test of abstract reasoning and a test of speed and accuracy in relatively young (47 years of age) surgically menopausal women who had been given a bolus intramuscular injection of 10 mg E2 every month for 3 months. These effects were from small studies from a single research group. It remains to be determined whether factors such as an older age (> 69 years of age), type of menopause (surgical or natural) and type of treatment (E2 with or without a progestagen), mode of delivery (transdermal, oral or intramuscular), dosage and duration (> 3 months) could alter the effect on memory functions to a clinically relevant level. In addition, whether the absence or presence of menopausal symptoms can modify treatment effects should be investigated in more detail. Longitudinal RCTs currently underway in the U.S.A., U.K. and Canada will be able to test these hypotheses by the year 2010.

Hormone replacement therapy to maintain cognitive function in women with dementia.

BACKGROUND: As estrogens have been shown to have several potentially beneficial effects on the central nervous system, it is biologically plausible that maintaining high levels of estrogens in postmenopausal women by means of estrogen replacement therapy (ERT) could be protective against cognitive decline and the development of Alzheimer's disease (AD) or other dementia syndromes. OBJECTIVES: To investigate the effects of ERT (estrogens only) or HRT (estrogens combined with a progestagen) compared with placebo in randomized controlled trials (RCTs) on cognitive function of postmenopausal women with dementia. SEARCH STRATEGY: The CDCIG Specialized Register, which contains up-to-date records from many medical databases was searched using the terms ORT, PORT, ERT, HRT, estrogen*, oestrogen*, progesteron* and Alzheim* on 16th of May 2002. In addition, MEDLINE (1966-2002/01); EMBASE (1985-2002/01); and PsyINFO (1967-2002/01) were searched. SELECTION CRITERIA: All double-blind randomized controlled trials (RCTs) into the effect of ERT or HRT for cognitive function with a treatment period of at least two weeks in postmenopausal women with AD or other types of dementia. DATA COLLECTION AND ANALYSIS: Abstracts of the references retrieved by the searches were read by two reviewers (EH and KY) independently in order to discard those that were clearly not eligible for inclusion. The two reviewers studied the full text of the remaining references and independently selected studies for inclusion. Any disparity in the ensuing lists was resolved by discussion with all reviewers in order to arrive at the final list of included studies. The selection criteria ensured that the blinding and randomization of the included studies was adequate. The two reviewers also assessed the quality of other aspects of the included trials. One reviewer (EH) extracted the data from the studies, but was aided and checked by JB from Cochrane. MAIN RESULTS: A total of five trials including 210 women with AD were analysed. Meta-analyses showed that there was a limited positive effect from low dosage of conjugated equine estrogens (CEE, 0.625 mg once a day) but not from higher dosage (1.25 mg of CEE once a day) on the Mini-Mental Status Examination after 2 months (WMD=1.28, 95% C.I.=0.26 to 2.30, z=2.45, p<0.01) and the effect disappeared after 3, 6 and 12 months of treatment. This effect was small and not clinically relevant as there was only a difference of 1 point on average in comparison with the placebo users (the scale range is 0-30). There were also short-term effects of 1.25 mg of CEE on tests of concentration and executive function, namely the Trail Making Test-B (WMD=-40.90, 95% C.I.-79.29 to -2.51, z=2.09, p<0.05) and Digit Span backward (WMD=0.67, 95% C.I.=-0.01 to 1.34, z=1.94, p<0.05). With regard to memory, only cued delayed recall of a word list was positively affected by 2 months of transdermal diestradiol (E2) (WMD=6.50, 95% C.I.=4.04 to 8.96, z=5.19, p<0.0001). No HRT effects were seen on other word lists, Paragraph Recall or Paired Associate Learning. In addition, no effects were seen on visual memory, language functions, most speeded tests, clinical rating scales or depression. Controls had better performance on the delayed recall of the Paragraph Test (overall WMD=-0.45, 95% C.I.=-0.79 to -0.11, z=2.60, p<0.01) after 1 month and on Finger Tapping after 12 months (WMD=-3.90, 95% C.I.=-7.85 to 0.05, z=1.93, p<0.05). Clinicians also gave controls a better score on a dementia rating scale (CDR, overall WMD=0.35, 95% C.I.=0.01 to 0.69, z=1.99, p<0.05). Positive findings in favour of treatment or placebo could have been random effects caused by multiple analyses. After correction for multiple testing, only the short-term positive treatment effect of E2 on memory remained. REVIEWER'S CONCLUSIONS: Currently, HRT or ERT for cognitive improvement or maintenance is not indicated for women with AD. As we did not have data on women with other types of dementia (e.g. vascular dementia) this remains to be investigated. As most studies only used CEE and our earlier review in healthy women found effects only after a bolus injection of E2, it remains possible that different preparations or types of ERT or HRT could have a different effects. Several questions are raised in this review, including whether factors such as age, dementia onset (early AD), or the use of a particular preparation for a longer duration of treatment could have different effects. Perhaps the most important question is whether ERT or HRT can delay the time of onset of dementia. For answers to these questions, we have to await the results of the large RCTs currently in progress in the UK, USA, and Canada.

Salivary cortisol and DHEA: association with measures of cognition and well-being in normal older men, and effects of three months of DHEA supplementation.

Dehydroepiandrosterone (DHEA) is a steroid that shows a marked age-related decline in humans. Previous research suggests potential for DHEA replacement in old age to enhance cognition and well-being. We conducted a clinical trial to test these hypotheses in a non-clinical sample of 46 men aged 62-76. Participants received either 50 mg DHEA daily for 13 weeks, followed by placebo for 13 weeks, or the reverse, in a randomised double-blind cross-over trial design. Levels of salivary cortisol and DHEA were measured at 0800 h and 2000 h prior to each assessment session. Cognition was assessed with tests of speed, attention and episodic memory. Well-being was measured with questionnaires of mood and perceived health. Mood questionnaires were completed at the assessment session as well as concurrently with saliva sampling.A correlational analysis of baseline behavioural data with hormonal data, controlling for age, revealed that higher morning DHEA was associated with lower confusion (r=-0.33; P=0.04), while higher evening DHEA was associated with lower anxiety (r=-0.35; P=0.03) and lower current negative mood in the morning (r=-0.37; P=0.03). Conversely, higher morning cortisol and a morning cortisol/DHEA ratio were associated with higher anxiety (r=0.35; P=0.03), (r=0.46; P=0.004), general mood disturbance (r=0.32; P=0.046), (r=0.32; P=0.04) and higher current negative mood in the evening (r=0.37; P=0.03), (r=0.38; P=0.03). A higher morning cortisol/DHEA ratio was also associated with higher confusion (r=0.39; P=0.01) and lower visuo-spatial memory performance (r=-0.39; P=0.01). Unexpectedly, higher evening cortisol was associated with faster choice reaction time (r=-0.33; P=0.04). These findings are consistent with an impairing effect of high cortisol on episodic memory and mood in older men, which may be attenuated by DHEA. When treatment effects were analysed, no significant effects of DHEA were observed on any of the trial outcomes, providing no support for benefits of DHEA supplementation for cognition or well-being in normal older men in the shorter-term.

Dehydroepiandrosterone (DHEA) supplementation for cognitive function .

BACKGROUND: In view of the theoretical rationale for beneficial effects of DHEA and DHEAS on cognitive function in ageing and dementia, we have undertaken a thorough investigation of well-conducted studies in this area. This will provide a basis for confirmation of any effect of DHEA/S administration in humans in properly controlled trials. The review will also provide a scientific basis for effective dosage, acceptable route and duration of administration, and side effect profiles. This review is especially pertinent at this time as DHEA is currently being sold in large quantities in health food stores, particularly in the USA. In some cases the recommended dose is different for men and women (50mg/day for men and 25mg/day for women) and the basis for this recommendation needs to be explored. OBJECTIVES: To establish whether administration of DHEA, or its sulphate, DHEAS, improves cognitive function or reduces the rate of decline of cognitive function in normal older adults or in individuals with dementia. SEARCH STRATEGY: Relevant electronic databases, journals, personal communications and conference abstracts were searched for randomised controlled trials investigating the effects of DHEA/S on cognition in older adults. SELECTION CRITERIA: All relevant randomised controlled trials of DHEA/S were considered for inclusion in the review. DATA COLLECTION AND ANALYSIS: Data for the specified outcomes were independently extracted by two reviewers (FAH & JvN) and cross-checked. Any discrepancies were discussed and resolved. No data pooling was undertaken owing to the lack of availability of the relevant statistics. MAIN RESULTS: There are four included studies, three cognition in normal older people, and Barnhart 1999 in perimenopausal women with decreased well-being. There were no studies in dementia. There were a few significant findings. Wolf 1997 found significant improvement following DHEA compared with placebo in both immediate recall (MD 0.8, 95% CI 0.16, 1.44) and delayed recall (MD 0.9, 95% CI 0.09, 1.71) of a visual memory test in women, estimated in a crossover trial after 2 weeks of treatment with each of DHEA and placebo. However there was no significant improvement in men, nor a significant effect on a verbal memory test. There was also no significant effect on four other cognitive tests. Wolf 1998 (2) found that placebo group performance deteriorated significantly on a test of selective attention following a psychosocial stressor (p<0.05), while deterioration was not evident in the DHEA group (p=0.85) after two weeks of treatment. However, when compared to placebo, DHEA produced a significant impairment on a visual memory test (p<0.01) following the stressor. No significant effect was found on a third cognitive task. Effects were not found on tasks when administered in the absence of a stressor. Barnhart 1999 employed three cognitive measures and found no significant effect of DHEA compared with placebo at 3 months. Findings to date suggest that DHEA replacement seems to be well tolerated with an absence of significant side-effects. REVIEWER'S CONCLUSIONS: The data offer no support at present for an improvement in memory or other aspects of cognitive function following DHEA treatment in normal older people. In view of the growing public enthusiasm for DHEA supplementation, particularly in the USA, and the possibility that any neuroprotective effect of DHEA/S may only be evident in the long term, there is a need to undertake high quality trials in which the duration of DHEA treatment is longer than one year, and the number of participants is large enough to detect effects if they exist. Recently, trials of DHEA supplementation in Alzheimer's Disease (USA), post-menopausal women (USA), normal older men (UK), and a one-year trial in normal older men and women (France) have been completed. As soon as the results are available these studies will be included in the review.

Population norms for the MMSE in the very old: estimates based on longitudinal data. Mini-Mental State Examination.

OBJECTIVE: To report the percentile distribution of Mini-Mental State Examination (MMSE) scores in older people by age, sex, and education level, estimated from longitudinal data, after correcting for loss due to dropout. METHODS: The Cambridge City over 75 Cohort is a population-based study of a cohort of 2106 subjects age 75 years and older at study entry followed up over 9 years. At each of the four waves, cognitive function was assessed using MMSE. Based on these data, the relationship between age and MMSE score was modeled. Percentile distributions by age, sex, and education level were provided using inverse probability weighting to correct for dropouts. RESULTS: Performance on MMSE was related to age in men and women. In women, at age 75, MMSE score ranged from 21 (10th percentile) to 29 (90th percentile). At age 95, the range was 10 (10th percentile) to 27 (90th percentile). The upper end of MMSE distribution was slightly modified with age, whereas the lower end of the distribution was very sensitive to age effect. A similar pattern was observed in both sexes. CONCLUSION: These findings provide norms for MMSE scores in subjects age 75 years and older from longitudinal population-based data. Such norms can be used as reference values to determine where an individual's score lies in relation to his or her age, sex, and education level.

Decline across different domains of cognitive function in normal ageing: results of a longitudinal population-based study using CAMCOG.

Dementia is an important cause of disability in the elderly. There is evidence that cognitive impairment in dementia is on a continuum with cognitive impairment in the non-demented elderly. In order to investigate this possibility, we need detailed knowledge about the population distribution of cognitive function and change in cognitive function. The aim of this study is to describe the change in different domains of cognitive function over 4 years in a population-based sample of non-demented elderly people, and to investigate the effect of sociodemographic variables and baseline cognitive function on change in each of the cognitive domains. Respondents from two group general practice lists (n = 503) were interviewed using the Cambridge Cognitive Examination (CAMCOG) at the incidence wave of the Cambridge City Over-75 Cohort Study and after a mean time period of 3.9 years. One hundred and thirty five of 212 non-demented subjects seen at follow-up completed the CAMCOG at both interviews. The annual rate of change in total CAMCOG score was -1.6 points per year (p < 0.001). There was statistically significant decline in all of the CAMCOG subscales. Greater decline in the Memory subscale was associated with less education (p = 0.03). Greater decline in the Attention/Calculation subscale was associated with manual social class (p = 0.05). Greater decline in the Perception subscale was associated with older age (p = 0.03). Decline in specific cognitive domains may indicate a reversible phase of cognitive impairment and deserves further investigation.

Healthy ageing in urban and rural Britain: a comparison of exercise and diet.

OBJECTIVE: to compare exercise levels, and dietary intake of fruit and vegetables in representative samples of healthy elderly people living in rural and urban areas. DESIGN: two-wave (screening followed by face-to-face interview) cross-sectional survey. SETTING: rural Cambridgeshire and urban Nottingham, UK. PARTICIPANTS: 2041 respondents (1021 in Cambridgeshire; 1020 in Nottingham) sampled from general practitioner lists. MAIN OUTCOME MEASURES: self-rated reports of health, exercise and food frequency. RESULTS: within these samples of healthy elderly people, those living in rural Cambridgeshire were significantly more likely to consume fresh fruit [odds ratio (OR) = 1.81, 95% confidence interval (CI) = 1.52-2.16, P < 0.001] and green vegetables (OR = 3.70, 95% CI = 3.07-4.45, P < 0.001) daily in both the summer and winter months. While overall levels of activity were similar for both groups, the structure of activities differed, with the urban sample reporting significantly greater time spent walking. CONCLUSIONS: against current World Health Organisation recommendations for fruit and vegetable consumption, respondents in rural areas reported a substantially 'healthier' diet than their urban peers. On the other hand, urban elderly people may enjoy greater cardiovascular protection from greater time spent walking.

Very old drivers: findings from a population cohort of people aged 84 and over.

BACKGROUND: Increases in longevity will involve a significant increase among the number of drivers in the very old, who are at greater risk of being involved in road accidents. Data are thus needed from studies of older populations to characterize those still driving, the reasons for giving up and to help formulate appropriate policies for dealing with the problems faced and created by an increase in older drivers. METHODS: A driving questionnaire was administered to surviving members of a cohort comprising a representative sample of individuals aged >/=84, the Cambridge City over 75 Cohort. Out of 546 survivors 404 completed the driving questionnaire at the 9-year follow-up. In addition, subjects were assessed, at baseline and at each follow-up, for cognitive performance using the Mini-Mental State Examination (MMSE) and for physical impairment using the Instrumental of Activities in Daily Living (IADL) scale. RESULTS: Of the sample, 37% had driven in the past, and 8.4% were still driving, the majority regularly. The drivers tended to be younger (mean age 86.6 years), men (71%) and to be married (67.7%). Although physical disability and cognitive impairment are common in this age group, current drivers had few physical limitations on their daily activities and were not impaired on MMSE. None of the current drivers had visual impairment and 22.6% had hearing loss. Of those who had given up driving, 48.5% had given up at the age of >/=80. The commonest reasons for giving up driving were health problems (28.6%), and loss of confidence (17.9%). One-third reported giving up driving on advice. CONCLUSION: A process of self-selection takes place among older drivers. People over the age of 84 who are still driving have generally high levels of physical fitness and mental functioning, although some have some sensory loss. Given the likely increase in the number of older drivers over the next decades, safety will be improved most by strategies aimed at the entire driving population with older drivers in mind, rather than relying on costly screening programmes to identify the relatively small numbers of impaired older people who continue to drive.

Staging of cytoskeletal and beta-amyloid changes in human isocortex reveals biphasic synaptic protein response during progression of Alzheimer's disease.

We have examined the relationships between dementia, loss of synaptic proteins, changes in the cytoskeleton, and deposition of beta-amyloid plaques in the neocortex in a clinicopathologically staged epidemiological cohort using a combination of biochemical and morphometric techniques. We report that loss of synaptic proteins is a late-stage phenomenon, occurring only at Braak stages 5 and 6, or at moderate to severe clinical grades of dementia. Loss of synaptic proteins was seen only after the emergence of the full spectrum of tau and beta-amyloid pathology in the neocortex at stage 4, but not in the presence of beta-amyloid plaques alone. Contrary to previous studies, we report increases in the levels of synaptophysin, syntaxin, and SNAP-25 at stage 3 and of alpha-synuclein and MAP2 at stage 4. Minimal and mild clinical grades of dementia were associated with either unchanged or elevated levels of synaptic proteins in the neocortex. Progressive aggregation of paired helical filament (PHF)-tau protein could be detected biochemically from stage 2 onwards, and this was earliest change relative to the normal aging background defined by Braak stage 1 that we were able to detect in the neocortex. These results are consistent with the possibility that failure of axonal transport associated with early aggregation of tau protein elicits a transient adaptive synaptic response to partial de-afferentation that may be mediated by trophic factors. This early abnormality in cytoskeletal function may contribute directly to the earliest clinically detectable stages of dementia.

Incidence and course of dementia in people with Down's syndrome: findings from a population-based study.

The prevalence rate of Alzheimer's disease (AD) in people with Down's syndrome (DS) increases significantly with age. However, the nature of the early clinical presentation, course and incidence rates of dementia are uncertain. The aims of the present study were to investigate the characteristics of age-related clinical changes and incidence rates for dementia in a population-based sample of people with DS aged 30 years and older at the age of risk for dementia. A modified version of the Cambridge Examination for Mental Disorders of the Elderly informant interview was used to determine the extent and nature of changes in memory, personality, general mental functioning and daily living skill 18 months after a similar assessment At the time of the first assessment, the initial changes reported were predominately in behaviour and personality. At the second assessment, overall estimated incidence rates for frontal-like dementia were high (0.24), mainly in the younger groups, with incidence rates of AD, meeting both ICD-10 and DSM-IV criteria, of 0.04 predominately in the older groups. The present authors have hypothesized that the observed personality changes and the high estimated incidence rates of frontal-like dementia in the younger groups may indicate that functions served by the frontal lobes are the first to be compromised with the progressive development of Alzheimer-like neuropathology in people with DS.

Dehydroepiandrosterone (DHEA) supplementation for cognition and well-being.

BACKGROUND: In view of the theoretical rationale for beneficial effects of DHEA and DHEAS in aging and dementia, we believe it is timely to undertake a thorough investigation of well-conducted studies in this area. This will provide a basis for confirmation of any effect of DHEA/S administration in humans, in large-scale and properly controlled trials, which would evaluate effective dosage, acceptable route and duration of administration and side effect profiles. This is especially pertinent at this time as DHEA is currently being sold in large quantities in health food stores, particularly in the USA. In some cases the recommended dose is different for men and women (50mg/day for men and 25mg/day for women) and the basis for this recommendation needs to be explored. OBJECTIVES: To establish whether administration of DHEA, or its sulphate, DHEAS, improves psychological well-being and/or improves cognitive function or reduces the rate of decline of cognitive function in older adults or in individuals with dementia. SEARCH STRATEGY: All available electronic databases, hand searched journals, personal communications and conference abstracts were searched for randomised controlled trials of DHEA in well-being and cognition. The total yield from searching was 415 and the detailed breakdown is given in the body of this review. SELECTION CRITERIA: All relevant randomised controlled trials of DHEA or DHEAS were considered for inclusion in the review. Studies where groups are matched, rather than randomised, were also considered. DATA COLLECTION AND ANALYSIS: Data for the specified outcomes were independently extracted by two reviewers (FAH & JvN) and cross-checked. Any discrepancies were discussed and resolved. Where possible and appropriate, data were pooled and the mean differences estimated. MAIN RESULTS: The published DHEA trials fall into 2 categories: 1. four German studies in which DHEA was administered for a period of two weeks or less; 2. a USA study in which DHEA was administered for three months. Well-being was assessed in both sets of studies and a significant improvement was reported in the longer duration USA study, while no effect was reported in the shorter duration studies. The USA study used an open-ended questionnaire for self-assessment of well-being and stated that 67% of men and 82% of women reported enhanced well-being on DHEA compared with placebo. There was no significant change on an analogue measure of libido. The German studies assessed mood and well-being with a number of standardised scales and reported no significant effects of DHEA on any of them. Only the German studies examined performance on cognitive tests, i.e. memory, verbal fluency, speed of processing, etc. They reported no significant benefit of DHEA. REVIEWER'S CONCLUSIONS: The data at present offer limited support for improvement in a sense of well-being following DHEA treatment. This effect was reported only in the longer-term study which used a crude measure of well-being. The data offer no support at present for an improvement in memory or other aspects of cognitive function following DHEA treatment, although cognitive function was only measured in the short-duration trials. In view of the growing public enthusiasm for DHEA supplementation, particularly in the USA, it is clear that high-quality trials need to be undertaken in older adults, in which (a) the duration of DHEA treatment is in excess of two weeks, (b) the number of participants is large enough to detect effects if they exist, and (c) the outcome measures include validated scales for assessment of mood and well-being, and objective tests of cognitive function. Recently, studies of DHEA supplementation in clinical depression and Alzheimer's Disease have been completed in the USA. As soon as the results are available these studies will be reviewed. Currently, two trials (in France and the USA) in normal elderly are in progress.

Neuropathological findings in the very old. Results from the first 101 brains of a population-based longitudinal study of dementing disorders.

We report a unique longitudinal epidemiological study of cognitive decline in the elderly population of the city of Cambridge, UK. A population sample of people aged 75 and over was surveyed between 1984-1996 (n = 2,616) and followed 2.4, 6, and 9 years later. CAMDEX diagnostic criteria were used for clinical assessment, and the neuropathological protocol (in 101 cases) was based on the CERAD method, with additional features to allow Braak staging of neurofibrillary pathology. The main findings are of the heterogeneity of lesions to be found in very old populations, and the existence of considerable overlap in the pathologies found in the demented and nondemented. It seems that white matter (ischemic) pallor an amyloid angiopathy, as well as neuritic plaques, neurofibrillary tangles and Lewy body formation are all lesions that increase the likelihood of dementia.