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Clive Holmes

Publications and source records attributed to Clive Holmes.

23 records · Page 2Linked to original sources
PubMed2002

Genotype and phenotype in Alzheimer's disease.

BACKGROUND: Patients with Alzheimer's disease show a wide variation in clinical phenotype. Genetic research has been largely concerned with the role of mutations or common variants as risk factors for the disease. Do genetic factors also influence clinical phenotype? AIMS: To examine the evidence that genetic factors influence the clinical expression of the disease in addition to influencing risk. METHOD: A selective review was made of the key literature. RESULTS: Mutations in three genes, coding for amyloid precursor protein, presenilin-1 and presenilin-2, and a common variation (epsilon4) in another gene, APOE, have been shown to lead to an earlier development of the disease. More recently, genetic association and twin studies have suggested a role for genetic factors in the development of other aspects of clinical phenotype, notably the appearance of non-cognitive symptoms. CONCLUSIONS: In Alzheimer's disease genetic variation influences a number of aspects of clinical phenotype.

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Does lithium therapy protect against the onset of dementia?

Lithium compounds might theoretically play a role in preventing dementia by inhibiting formation both of beta amyloid and hyper phosphorylated tau protein. We carried out a case-control study to assess any possible clinical effects of lithium therapy on the diagnosis of dementia, using data from the General Practice Research Database, which collects routine data from primary care patients in the UK. Patients who received lithium had a higher risk of a diagnosis of dementia compared with those who did not (adjusted odds ratio 1.8, 95% CI 1.1-2.8). There was a trend toward increasing risk with increasing numbers of lithium prescriptions. This evidence does not support the use of lithium for preventing dementia.

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Association between dementia and infectious disease: evidence from a case-control study.

Inflammation plays a part in the etiology of dementia. Whether this is the primary pathogenesis, or a secondary reaction is unclear. We postulate that since systemic infection can provoke the enhanced synthesis of inflammatory mediators in the brain, such diseases may promote the onset of dementia. We carried out a nested case-control study using the General Practice Research Database. Cases were patients with incident dementia, and controls without such a diagnosis. Infectious episodes in the four years preceding diagnosis were counted using diagnostic codes, or prescription codes for anti-infective drugs. We considered age, sex, smoking, diabetes mellitus, and frequency of consultation as potential confounders. There were 9954 valid cases, and 9374 valid controls. Cases were on average older, more likely to be female, to smoke and to have diabetes, than the controls. There was an increased risk of diagnosis of dementia in those patients older than 84 with infections (OR for 2 or more infections compared with 0 or 1 = 1.4, 95% CI 1.2 to 1.7). Smoking and diabetes mellitus were also shown to markedly increase the risk of diagnosis of dementia. We have shown a positive association between episodes of infection and increased likelihood of diagnosis of dementia in the very elderly. Smoking and diabetes mellitus are associated with onset of dementia in the elderly. The evidence from this study may represent cause and effect, since there is a credible biologic explanation.

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The effect of link nurses on hospital readmission rates.

This study investigates whether visits to a patient early post-discharge by a member of the ward team (locality link nurse) reduces psychiatric hospital readmission rates for older people and improves the physical and psychological state of the patient. This is a summary of the paper the full version can be accessed at nursingtimes.net.

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