Diabetes and dementia in older people: a Best Clinical Practice Statement by a multidisciplinary National Expert Working Group.

Both dementia and diabetes mellitus are long-term disabling conditions and each may be a co-morbidity of the other. Type 2 diabetes is associated with a 1.5- to 2-fold higher risk of dementia. Diabetes also may occur for the first time in many individuals with mental ill health, including cognitive impairment and dementia, and this may complicate management and lead to difficulties in self-care. Case finding is often poor for cognitive impairment in medical settings and for diabetes in mental health settings and this needs to be addressed in the development of care pathways for both conditions. Many other deficiencies in quality care (both for dementia and diabetes) currently exist, but we hope that this Best Clinical Practice Statement will provide a platform for further work in this area. We have outlined the key steps in an integrated care pathway for both elements of this clinical relationship, produced guidance on identifying each condition, dealt with the potentially hazardous issue of hypoglycaemia, and have outlined important competencies required of healthcare workers in both medical/diabetes and mental health settings to enhance clinical care.

Brief report: Use of the Mini-Cog as a screening tool for cognitive impairment in diabetes in primary care.

The Mini-Cog was shown to be a brief, acceptable and practical cognitive screen for older people with diabetes when administered by a primary care nurse. It could be integrated easily into the annual diabetes review and help to identify those who may benefit from extra help with their management.

Caring for older adults with diabetes mellitus: characteristics of carers and their prime roles and responsibilities.

AIMS: Expanding prevalence of diabetes has a major health impact on older people and the burden experienced by their informal carers. We report research which aimed to examine the burden on carers and highlight their input into diabetes care. METHODS: Of 98 diabetes patients aged over 59 years, 89 regularly received help with day-to-day activities or looking after from someone else and, of these, 83 carers consented to interview. Patients and carers were administered questionnaires related to the management of diabetes and personal strain (including Diabetes Knowledge Questionnaire, EuroQol, Caregiver Strain Scale and General Health Questionnaire). RESULTS: A substantial unmet need of older people with diabetes mellitus, in relation to domestic activities and diabetes care, was highlighted. Patient and carer diabetes knowledge was low. Primary carers were generally female relatives from the same household, not in paid employment. Twenty-seven carers (33%) provided > or = 35 h of care work each week. Most carers experienced a moderate level of stress, but 11 (14%) regularly felt overwhelmed. Thirty-three carers (40%) said they had never received any information on diabetes from professionals. Help most frequently wanted was advice and support in relation to accessing community services and about finances, benefits and/or allowances. CONCLUSIONS: Both patient and carer diabetes education strategies are required. Instruction for carers in the basic care of patients with diabetes is also needed and should be targeted. As many as one in seven carers felt regularly overwhelmed and lacked adequate support. Finally, 26 carers (31%) were entitled to benefits which they did not claim.

Prevalence and pattern of cognitive impairment in a community cohort of men in South Wales: methodology and findings from the Caerphilly Prospective Study.

BACKGROUND/AIMS: The prevalence of dementia and cognitive impairment not dementia was investigated in the Caerphilly Prospective Study cohort (men currently aged 65-84 years). METHODS: Of 1,633 men eligible for cognitive screening, 1,225 (75%) were seen, with those failing the screening criteria (CAMCOG <83 or decline in CAMCOG >9) being neurologically examined. RESULTS: For dementia, diagnosed by DSM-IV criteria, the population prevalence was 5.2% rising to 6.1% in the screened population. For cognitive impairment not dementia, the prevalence in the screened population was 15.6% giving an overall prevalence of cognitive impairment of 21.8%. Prevalence rose fivefold between ages of 65 and 84 years to reach over 50%. CONCLUSION: These figures are likely to underestimate actual prevalence in this population, and developing effective interventions should be a public health priority.

Evaluation of the safety and immunogenicity of synthetic Abeta42 (AN1792) in patients with AD.

BACKGROUND: Abeta42-immunization reduces plaque burden and improves cognition in transgenic mouse models of Alzheimer disease (AD). This phase 1 study evaluated the safety, tolerability, and immunogenicity of AN1792 (human aggregated Abeta42) in patients with mild to moderate AD. METHODS: Twenty patients were enrolled into each of four dose groups and randomly assigned to receive IM AN1792 (50 or 225 microg) with QS-21 adjuvant (50 or 100 microg) or QS-21 only (control) in a 4:1 active:control ratio on day 0 and at weeks 4, 12, and 24. Patients could receive up to four additional injections of a polysorbate 80 modified formulation at weeks 36, 48, 60, and 72. Safety, tolerability, immunogenicity, and exploratory evidence of efficacy were evaluated. RESULTS: Treatment-related adverse events were reported in 19 (23.8%) patients, but no relationship was observed between AN1792 dose and incidence. One patient developed meningoencephalitis that was diagnosed after death (not directly related to study treatment) and 219 days after discontinuing from the study. Five deaths occurred during the study follow-up, but none was considered to be directly related to study treatment. During the period of the first four injections, 23.4% of AN1792-treated patients had a positive anti-AN1792 antibody titer (an anti-AN1792 antibody titer of > or =1:1,000). This increased to 58.8% after additional injections with the modified formulation. Disability Assessment for Dementia scores showed less decline among active compared with control patients at week 84 (p = 0.002). No treatment differences were observed in three other efficacy measures. CONCLUSIONS: AN1792 + QS-21 elicited a positive antibody response to Abeta42 in more than half of this elderly study population.

Prevalence of diabetes in care home residents.

OBJECTIVE: To determine the prevalence of known and undetected diabetes diagnosed either by an elevated fasting baseline sample or by a 2-h post-glucose load sample in a group of residents of care homes in an urban-district setting. RESEARCH DESIGN AND METHODS: We completed individual interviews with patients and caregivers in 30 care homes (both residential and nursing homes) in two metropolitan districts of Birmingham, West Midlands, U.K. All care homes were under the supervision of primary care physicians (general practitioners). We carried out 75-g oral glucose tolerance tests (OGTTs) in consenting residents without previous known diabetes. Criteria for diagnosis of diabetes were obtained from the World Health Organization (1998) and the American Diabetes Association (1997). RESULTS: Of 636 residents available for study, 76 residents (12.0%) were known to have diabetes; of the 560 remaining residents, 286 either refused to participate or were deemed too ill or unavailable to undergo testing. Complete data on 274 OGTTs were obtained (median age 83 years, range 45-101). A total of 46 subjects were diagnosed as having diabetes and 94 as having impaired glucose tolerance. Allowing for subjects who refused or were unable to participate, the calculated total prevalence (which includes known and newly detected diabetes) was 26.7% (95% CI 21.9-32.0). The calculated overall prevalence of impaired glucose tolerance was 30.2% (25.2-35.6). CONCLUSIONS: In a group of care home residents not known to have diabetes and able to undergo testing, a substantial proportion have undetected diabetes based on a 2-h postglucose load. These residents warrant further study as they may be at higher cardiovascular risk and require an intervention.

Age and gender bias in statin trials.

Cardiovascular disease is strongly age-related, and is the leading cause of death in older people. Several well-publicized trials have recently reported that statin drugs (HMG CoA reductase inhibitors) are effective in lowering cholesterol and in reducing the risk of myocardial infarction and stroke. In order to determine whether the results of these trials are relevant to our ageing population, we examined the representation of older people and women in randomized controlled trials of statin drugs. A systematic search of the medical literature from 1990 to 1999 was done to identify randomized placebo-controlled trials of statin drugs which evaluated clinical end-points-myocardial infarction, stroke or death. We identified 19 trials: 15 secondary prevention and four primary prevention. The mean age, age range and gender of the participants in these trials were determined. In the secondary prevention trials, the total number of patients randomized was 31683, with a combined mean age of 58.1 years. No trial enrolled people beyond the age of 75 years, and only 23% of the trial population was female. The four primary prevention trials randomized a combined total of 14 557 subjects with a mean age of 56.9 years. Only 10% of study participants were female. Statin drug trials have suffered from age and gender bias, having been mainly conducted in middle-aged male populations. The extrapolation of evidence from these trials to older people and women needs further evaluation.

Cognitive dysfunction in older subjects with diabetes mellitus: impact on diabetes self-management and use of care services. All Wales Research into Elderly (AWARE) Study.

OBJECTIVE: To determine whether cognitive impairment is associated with changes in self-care behaviour and use of health and social services in older subjects with diabetes mellitus. RESEARCH DESIGN AND METHODS: This was a community based, case-control study of subjects registered with general practices participating in the All Wales Research into Elderly (AWARE) Diabetes Study. The 396 patients aged 65 years or older with known diabetes mellitus were compared with 393 age- and sex-matched, non-diabetic controls. Adjusted odds ratio estimates of normal performance on Mini-Mental State Examination (MMSE) and Clock Drawing Test (numbers and hands) were determined. Information on self-care behaviours and use of services was obtained. RESULTS: A total of 283 (71%) diabetic subjects scored 24 or more on MMSE, compared with 323 (88%) of controls (OR 0.54, P<0.0005). The mean (S.D.) scores were 24.5 (5.1) and 25.7 (4.3), respectively (difference between means 1.22; 95% CI 0.56, 1.88; P<0. 001). Clock testing demonstrated that 257 (65%) and 286 (72%) diabetic subjects correctly placed the numbers and hands, respectively, compared with 299 (76%) and 329 (84%) of controls (OR 0.59, P<0.001 and P<0.52, P<0.0005, respectively). Both test scores declined with increasing age, earlier school leaving age and deteriorating visual acuity. Of other variables examined, only need for oral hypoglycaemic drugs or insulin, history of stroke, dementia or Parkinson's disease and symptoms of autonomic neuropathy significantly impaired one or more cognitive test scores. The odds ratios (95% CI) for normal cognitive test results in subjects with diabetes after adjusting for all significant variables was 0.74 (0. 56, 0.97), P=0.029 for MMSE scores and 0.63 (0.44, 0.93), P=0.019, and 0.58 (0.38, 0.89), P=0.013, for the numbers and hands parts of the clock test, respectively. In comparison with diabetic subjects with no evidence of cognitive impairment, diabetic subjects with an MMSE score <23 were significantly less likely to be involved in diabetes self-care (P<0.001) and diabetes monitoring (P<0.001). A low MMSE score was also significantly associated with higher hospitalisation in the previous year (P=0.001), reduced ADL (activities of daily living) ability (P<0.001) and increased need for assistance in personal care (P=0.001). CONCLUSIONS: Elderly subjects with predominantly Type 2 diabetes mellitus display significant excess of cognitive dysfunction, associated with poorer ability in diabetes self-care and greater dependency. Routine screening of cognition in older subjects with diabetes is recommended.

Older adults, diabetes mellitus and visual acuity: a community-based case-control study.

MAIN OBJECTIVES: to screen for impaired distance visual acuity in older adults living at home, both with and without diabetes mellitus to determine whether diabetes increases the likelihood of visual impairment and to identify associated factors. DESIGN: case-control study. SETTINGS: three districts of Wales: North Clwyd, Powys and South Glamorgan, with assessments in subjects' homes. SUBJECTS: 385 with diabetes mellitus and 385 age- and sex-matched controls. MAIN OUTCOME MEASURES: visual acuity measures, short form (SF)-36 quality of life scores RESULTS: we observed impairment of visual acuity in 40% of those with diabetes mellitus and 31% of controls. Diabetes was associated with an increased risk of visual impairment [odds ratio 1.50 (95% confidence interval 1.09-2.05), P = 0.013]. The pinhole test identified uncorrected refractive error in 11% of the 63 patients with diabetes and 12% of the 49 controls who wore glasses, and in 51% of the 91 patients and 84% of the 69 controls who did not wear glasses (P < 0.001). Increasing age (P < 0.001) and female sex (P = 0.014) were significantly associated with visual impairment in both groups, whilst history of foot ulceration (P = 0.001), duration of diabetes (P = 0.018) and treatment with insulin (P < 0.001) were significantly associated with visual impairment in subjects with diabetes. We observed a significant association between impaired visual acuity and five domains of the SF-36 (physical and social functioning, mental health, vitality, and health perceptions; P < 0.01 in each case). CONCLUSION: older adults living at home have a high prevalence of uncorrected visual impairment. Diabetes mellitus is associated with significantly increased risk of visual loss. This impairment is associated with detriments in health-related quality of life. We recommend earlier use of optometry services and assessment of visual acuity by clinicians.

A review of quality of life in Alzheimer's disease. Part 1: Issues in assessing disease impact.

There are numerous methods available for assessing patients with Alzheimer's disease (AD) or other forms of dementia. Quality-of-life (QOL) assessment is unique among these methods, because the QOL concept itself includes a subjective component that is fundamental to its measurement. It could be argued that measuring quality of life is just as important as measuring disease severity, disease progression, symptom response, cognition, behavioural disturbance and activities of daily living when assessing the impact of disease and intervention in dementia. The subjective nature of quality of life provides healthcare professionals with the opportunity of incorporating the value systems of patients and their carers into their assessments. A systematic review was carried out to include the published data (and some unpublished data) on QOL assessment tools and instruments that claim to measure quality of life in dementia. Literature for this review was identified by a thorough search of computer databases (1980-1997) that included Medline, Embase, PsychLit and International Pharmaceutical Abstracts. Reports concerning the conceptualisation, development, validation, reliability, reproducibility, comprehensiveness, practicality and use of QOL instruments in dementia/AD were selected for review as well as papers documenting clinical drug trials in this therapeutic area. A number of measures or methods used in the literature for assessing the quality of life of patients with dementing illnesses were identified. It was decided to present the resulting review in 2 parts that correspond to the 2 main groups into which the instruments were categorised. The first (part 1) looks at measures used to assess the impact of disease as well as instruments at a developmental or testing stage. The second (part 2) includes instruments that claim to measure quality of life in studies documenting the impact of a drug in this therapeutic area. There are as yet no validated methods of assessing the quality of life of both patients with dementia and their carers at the same time. QOL outcomes for these 2 groups is closely, if not fundamentally, linked and yet most studies identified in this review concentrate on measuring the quality of life of either the patient or the carer alone. Although some researchers may be getting close conceptually, an instrument has yet to satisfy all the criteria necessary to become accepted as a gold standard for QOL assessment in dementing illness. The ideal instrument must show that it can reliably, reproducibly and comprehensively assess quality of life for patients with dementia and their carers. It should also demonstrate that it can measure quality of life effectively using a practical administration technique that does not place any unnecessary burden on either informal carers, other healthcare workers involved or the patient themselves. Further cross-sectional and longitudinal research is required to psychometrically test the available instruments as well as continuing conceptual research to explore new ways of assessing quality of life in this important area.

A review of quality of life in Alzheimer's disease. Part 2: Issues in assessing drug effects.

There are numerous methods available for assessing patients with Alzheimer's disease (AD) or other forms of dementia. Quality-of-life (QOL) assessment is unique among these methods. The subjective nature of quality of life provides healthcare professionals with the opportunity of incorporating the value systems of patients and their carers into their assessments. A systematic review was carried out to assess the published data (and some unpublished data) on QOL assessment tools and instruments that claim to measure quality of life in dementia. A number of measures or methods used in the literature for assessing the quality of life of patients with dementing illnesses were identified. It was decided to present the resultant review in 2 parts that correspond to the 2 main groups into which the instruments were categorised. The first (part 1), looked at measures used to assess the impact of disease as well as instruments at a developmental or testing stage. The second (part 2), includes instruments that claim to measure quality of life in studies documenting the impact of a drug in this therapeutic area. This second group consists mainly of instruments identified as being used to assess quality of life during clinical trials in dementia/AD. As in part 1, this part of the review was unable to identify any validated methods of assessing the quality of life of both patients with dementia and their carers at the same time. The ideal instrument must show that it can reliably, reproducibly and comprehensively assess quality of life for both patients with dementia and their carers. It should also demonstrate that it can measure quality of life effectively using a practical administration technique that does not place any unnecessary burden on either informal carers, other healthcare workers involved or the patient themselves. In addition, any measure intended for use in assessing the impact of drug treatment on quality of life must demonstrate sensitivity to change, also known as responsiveness. All these criteria are even more important when measuring quality of life as an outcome during clinical trials of a new antidementia drug, because the data generated are likely to influence decisions made by regulatory bodies about whether to grant licences that are required by pharmaceutical companies to market their products. Further cross-sectional and longitudinal research is required to ensure that the available instruments possess the essential psychometric criteria that must be demonstrated prior to their utilisation in clinical trials of any compound developed for use in dementia/AD. Ongoing conceptual research may still be useful in exploring new ways of assessing quality of life in this important therapeutic area.

Altered plasma antioxidant status in subjects with Alzheimer's disease and vascular dementia.

OBJECTIVES: Oxygen-free radicals and lipid hydroperoxides may have an aetiological role in the development of lesions in the central nervous system in patients with Alzheimer's disease and in those with vascular dementia. This study aimed to make a cross-sectional comparison of blood markers of oxidative stress in two groups of patients with these disorders and a control group. DESIGN: Cross-sectional comparative study. SETTING: Established memory clinics in Cardiff organized by a University Department of Geriatric Medicine within an acute care NHS Trust. METHODS: Following a dietary assessment, postprandial venous blood samples were obtained from the following: 25 subjects with probable Alzheimer's disease (AD) (mean age 74.3; 10 F, 15 M); 17 subjects with probable vascular dementia (VD) (mean age 75.5; 5 F, 12 M); and 41 controls (mean age 73.4; 24 F, 17 M) for measurement of circulating lipid peroxides (LP), total antioxidant capacity (TAC), vitamin C (VitC), vitamin E (VitE) and beta-carotene (BC). RESULTS: Plasma levels of VitC were significantly lower in subjects with vascular dementia compared with controls (VD, 6.5 (4.8, 8.2); controls, 10.0 (8.38, 11.6); VD vs controls, p = 0.015), but no significant difference was seen between controls and patients with Alzheimer's disease (AD, mean 8.3 (6.2, 10.4)). VitE levels were significantly lower in subjects with AD compared with controls (31.1 (28.2, 34.0) vs 36.0 (32.8, 39.2), p = 0.035). BC levels were similar in subjects with AD and controls, but significantly elevated in those with VD (AD, 0.28 (0.2, 0.34); VD, 0.40, (0.27, 0.53); controls, 0.28 (0.22, 0.34); VD vs controls, p = 0.046). There were no significant differences in LP or TAC between the three groups. CONCLUSIONS: Subjects with dementia attributed to Alzheimer's disease or to vascular disease have a degree of disturbance in antioxidant balance which may predispose to increased oxidative stress. This may be a potential therapeutic area for antioxidant supplementation.

No evidence that common allelic variation in the Amyloid Precursor Protein (APP) gene confers susceptibility to Alzheimer's disease.

In order to test the hypothesis that allelic variation within the Amyloid Precursor Protein (APP) gene influences susceptibility to common forms of Alzheimer's disease (AD) we screened the entire coding, promoter and 3' untranslated sequences of the APP gene for DNA variations in 30 unrelated patients and eight controls with probable AD by a combination of RT-PCR PCR and chemical cleavage mismatch analysis. Although we were unable to detect commonly occurring allelic variants, we were able to detect a novel mutation within the APP gene in one individual with late-onset AD. This mutation resulted in the substitution of a tryptophan residue for an arginine residue at codon 328 within exon 7 which encodes the so-called protease inhibitor domain of the 751 residue APP isoform. However, the pathological significance of this mutation is uncertain as neither this, nor any other mutation occurring within exon 7 of the APP gene was found in any of a further 102 AD patients and 86 age-matched controls. In conclusion, it is unlikely that susceptibility to AD results from commonly occurring allelic variants of the APP gene and it is even less probable that mutations within exon 7 of the APP gene are important risk factors for late-onset AD.

Symptoms of communication breakdown in dementia: carers' perceptions.

The breakdown of applied communication skills associated with the cognitive-communication deficit of dementia is poorly documented, as is carers' awareness of the nature of the problems. This study considered 32 symptoms which may be associated with breakdown of communication. Perceptions of these symptoms by carers of 79 community-living dementia patients were compared with perceptions of family/close friends of a comparable group of 76 control subjects. Communication skills of dementia patients were perceived to be significantly more impaired than those of control subjects. Areas of greatest discrepancy between performance of dementia and control groups included 'Asking the same question a number of times', 'Difficulty following conversation when a group of people are talking', 'Trouble keeping a conversation going' and 'Struggling to think of the names of people and places'. Eleven of the 32 symptoms were reported as occurring 'fairly often', 'usually' or 'always' in at least 50% of the dementia patients. Identification of specific factors likely to contribute to breakdown of communication in dementia will enable involved professionals to guide carers towards a better understanding of the problems. This should help to alleviate domestic stress thereby enhancing the quality of life of patients and their carers.

A retrospective study of myocardial infarction occurring in elderly patients in a coronary care unit.

Myocardial infarction is a major cause of morbidity and mortality particularly in the elderly. Coronary Care Unit monitoring has resulted in the improvement in prognosis in all age groups. In this study, the clinical course and outcome of 204 consecutive patients with acute myocardial infarction aged over 65 years is retrospectively analysed. All patients were managed in a Coronary Care Unit operating a needs related policy. Those under 75 years (120 patients) were compared to those over that age (84 patients). The groups differed in terms of clinical presentation, cardiac enzymatic rise and response to drug therapy. However they had similar complication rates, morbidity and mortality.

The apex cardiac beat: not a reliable clinical sign in elderly patients.

To assess its reliability as a marker of cardiomegaly in elderly patients, we compared a clinical assessment of heart size with that calculated from chest radiography. In 100 hospitalized subjects of median age 78 years, the apex beat was palpable in only 35% and its palpability declined with increasing age. Even when palpable, the apex beat had low specificity (74%) and sensitivity (69%) as a marker of cardiomegaly and its positive predictive value (69%) and negative predictive value (74%) were poor. The clinical assessment of heart size in elderly hospitalized patients should be interpreted with caution.