Detecting patients with Alzheimer''s disease suitable for drug treatment: comparison of three methods of assessment.

BACKGROUND. Therapy to enhance cholinergic function in the brain is under evaluation for the treatment of Alzheimer's disease. Tetrahydroaminoacridine (tacrine) has recently received a product licence in the United States of America for the treatment of Alzheimer's disease, and the licence application in the United Kingdom will shortly be reviewed. It is therefore possible that this drug will become available for use in the UK in due course. There will then be a need for screening procedures for a large number of elderly patients to decide whether or not they have dementia and, if so, whether it is the result of Alzheimer's disease and is suitable for treatment with the new drug. METHOD. A total of 246 patients aged 75 years or over in two general practices in Bristol were assessed to investigate the potential workload such screening would engender. Three different assessment schedules for the diagnosis of dementia were compared--the mini-mental state examination, the Kew test, and the abbreviated mental test score. RESULTS. None of the assessment schedules was found to be particularly onerous, with median times for administration of five, three and two minutes, respectively. A score of 23 or less on the mini-mental state examination was taken as the main cut-off point for further evaluation. Sixty six patients obtained this score--in 25 the low score reflected factors other than dementia, and 11 others declined further assessment. Of the remaining 30 patients only four had probable Alzheimer's disease at an appropriate level of severity for treatment, and lived with a carer who could ensure compliance and monitor side effects. Two of these patients were receiving conflicting medical treatment and a third declined therapy, leaving only one person for whom treatment could be prescribed. CONCLUSION. It seems likely that of those medically suitable for treatment, it may not be possible to prescribe tacrine for an appreciable proportion. Nevertheless, all potential patients should be screened as the procedures involved are not onerous and at least some of those found suitable for treatment are likely to benefit from this new approach.     

Herpesviruses in brain and Alzheimer's disease

It has been established, using polymerase chain reaction (PCR), that herpes simplex virus type 1 (HSV1) is present in a high proportion of brains of elderly normal subjects and Alzheimer's disease (AD) patients. It was subsequently discovered that the virus confers a strong risk of AD when in brain of carriers of the type 4 allele of the apolipoprotein E gene (apoE-epsilon4). This study has now sought, using PCR, the presence of three other herpesviruses in brain: human herpesvirus 6 (HHV6)-types A and B, herpes simplex virus type 2 (HSV2) and cytomegalovirus (CMV). HHV6 is present in a much higher proportion of the AD than of age-matched normal brains (70% vs. 40%, p=0.003) and there is extensive overlap with the presence of HSV1 in AD brains, but HHV6, unlike HSV1, is not directly associated in AD with apoE-epsilon4. In 59% of the AD patients' brains harbouring HHV6, type B is present while 38% harbour both type A and type B, and 3% type A. HSV2 is present at relatively low frequency in brains of both AD patients and normals (13% and 20%), and CMV at rather higher frequencies in the two groups (36% and 35%); in neither case is the difference between the groups statistically significant. It is suggested that the striking difference in the proportion of elderly brains harbouring HSV1 and HSV2 might reflect the lower proportion of people infected with the latter, or the difference in susceptibility of the frontotemporal regions to the two viruses. In the case of HHV6, it is not possible to exclude its presence as an opportunist, but alternatively, it might enhance the damage caused by HSV1 and apoE-epsilon4 in AD; in some viral diseases it is associated with characteristic brain lesions and it also augments the damage caused by certain viruses in cell culture and in animals.     

Identification of a new locus for autosomal dominant non-syndromic hearing impairment (DFNA7) in a large Norwegian family

Hereditary hearing impairment affects about 1 in 1000 newborns. In most cases hearing loss is non-syndromic with no other clinical features, while in other families deafness is associated with specific clinical abnormalities. Analysis of large families with non-syndromic and syndromic deafness have been used to identify genes or gene locations that cause hearing impairment. The present report describes a large Norwegian family with autosomal dominant non-syndromic, progressive high tone hearing loss with linkage to 1q21-q23. A maximum LOD score of 7.65 (theta = 0.00) was obtained with the microsatellite marker D1S196. Analysis of recombinant individuals maps the deafness gene (DFNA7) to a 22 cM region between D1S104 and D1S466. The region contains several attractive candidate genes. This report supports the idea of extensive genetic heterogeneity in hereditary hearing impairment and represents the first localization of a deafness gene in a Norwegian family.      

Multiple cerebral metastases: detectability with Gd-DTPA-enhanced MR imaging

Sixteen patients with suspected cerebral metastases were studied with magnetic resonance (MR) imaging before and after the intravenous administration of 0.1 mmol/kg of gadolinium diethylenetriaminepenta-acetic acid. The images were interpreted blindly by two neuroradiologists; all clinical, radiologic (computed tomographic and MR imaging), and pathologic data were reviewed to arrive at a final "best diagnosis," which was then compared with the prior blinded interpretations. Of seven patients found to have multiple metastases, six (86%) had at least one tumor nodule depicted by postinfusion MR imaging that was missed by one or both observers on review of preinfusion images alone. Lesions missed on preinfusion studies were usually small nodules hidden by or not detected next to regions of high-signal edema thought to be related to the adjacent tumor nodule. The authors believe that contrast enhancement improves detection of metastatic foci with MR imaging and that the findings indicate broader implications for the detection of multiple lesions from other causes.     

Changing Levels of Social Engagement with Gay Men Is Associated with HIV Related Outcomes and Behaviors: Trends in Australian Behavioral Surveillance 1998–2020

Archives of Sexual Behavior - Changes to how gay, bisexual, and other men who have sex with men (GBM) connect with each other and with their communities have implications for HIV prevention. Social...     

CLINICO-EPIDEMIOLOGICAL ALGORITHM FOR PREDICTING SYSTEMIC ARTERIAL HYPERTENSION AT HIGH ALTITUDE THROUGH MATHEMATICAL MODELLING

A population based hybrid design combining element of cohort and cross-sectional approach was used to develop a simple clinical algorithm to predict individual probability of developing hypertension (systolic BP > 140 mm Hg and/or diastolic BP > 90 mmHg). 3615 soldiers initially normotensive at the time of induction into high altitude, were studied by systematic random sampling. Multiple logistic regression analysis showed a high significant association between hypertension and age, body mass index (BMI), tobacco smoking and alcohol consumption. Using the constant/coefficient values obtained from the logistic model and the receiver operating characteristics (ROC) curve analysis, the following predictive rule was developed – To the age in years, add (BMIx 3.86); also add 5.53 if he is a smoker; and add 19.81 if he consumes alcohol. If the total exceeds 142, the individual is at high risk of developing hypertension. This algorithm carries a sensitivity of 68.2% and specificity of 78.5%.KEY WORDS: Hypertension, High altitude