Characteristics of a two-stage screen for incident dementia

Background and objectives: To avoid costly evaluation of healthy individuals, efficient methods of screening for incident dementia must combine adequate sensitivity and high specificity. Two-stage screening may offer improvements over single-stage methods. We therefore investigated a two-stage screening protocol for incident dementia among 3,308 elderly. Methods: We administered the Modified Mini-Mental-State (3MS) or, rarely, Jorm\u27s IQCODE, to a validation sample of 441 high-risk respondents. Informants then completed the Dementia Questionnaire (DQ). Finally, all 441 sample members underwent physical, neurologic, and neuropsychologic assessment. We studied the sensitivity and specificity of the 3MS/IQCODE and DQ using Receiver-Operating Characteristic analyses. Results: A 3MS cut point of 82/83 (of 100) yielded sensitivity and specificity of 91.5 and 90.1%. With 3MS scores of ⩽82, a DQ cut point of 2/3 (of five) yielded conditional sensitivity and specificity of 90.2 and 55.3%. Combining these instruments yielded sensitivity and specificity of 82.5 and 95.6%. Age stratification and use of longitudinal decline score criteria did not materially improve these figures. Conclusions: The improved specificity of the two-stage approach offers economies that are attractive, particularly if sensitivity can be enhanced, for example, by examination of a high-risk validation sample

The cholinergic system in the pathophysiology and treatment of Alzheimer's disease

Cholinergic synapses are ubiquitous in the human central nervous system. Their high density in the thalamus, striatum, limbic system, and neocortex suggest that cholinergic transmission is likely to be critically important for memory, learning, attention and other higher brain functions. Several lines of research suggest additional roles for cholinergic systems in overall brain homeostasis and plasticity. As such, the brain's cholinergic system occupies a central role in ongoing research related to normal cognition and age-related cognitive decline, including dementias such as Alzheimer's disease. The cholinergic hypothesis of Alzheimer's disease centres on the progressive loss of limbic and neocortical cholinergic innervation. Neurofibrillary degeneration in the basal forebrain is believed to be the primary cause for the dysfunction and death of forebrain cholinergic neurons, giving rise to a widespread presynaptic cholinergic denervation. Cholinesterase inhibitors increase the availability of acetylcholine at synapses in the brain and are one of the few drug therapies that have been proven clinically useful in the treatment of Alzheimer's disease dementia, thus validating the cholinergic system as an important therapeutic target in the disease. This review includes an overview of the role of the cholinergic system in cognition and an updated understanding of how cholinergic deficits in Alzheimer's disease interact with other aspects of disease pathophysiology, including plaques composed of amyloid-β proteins. This review also documents the benefits of cholinergic therapies at various stages of Alzheimer's disease and during long-term follow-up as visualized in novel imaging studies. The weight of the evidence supports the continued value of cholinergic drugs as a standard, cornerstone pharmacological approach in Alzheimer's disease, particularly as we look ahead to future combination therapies that address symptoms as well as disease progression

Reduced risk of Alzheimer\u27s Disease in Users of Antioxidant Vitamin Supplements: The Cache County Study

Background: Antioxidants may protect the aging brain against oxidative damage associated with pathological changes of Alzheimer disease (AD). Objective: To examine the relationship between antioxidant supplement use and risk of AD. Design: Cross-sectional and prospective study of dementia. Elderly (65 years or older) county residents were assessed in 1995 to 1997 for prevalent dementia and AD, and again in 1998 to 2000 for incident illness. Supplement use was ascertained at the first contact. Setting: Cache County, Utah. Participants: Among 4740 respondents (93%) with data sufficient to determine cognitive status at the initial assessment, we identified 200 prevalent cases of AD. Among 3227 survivors at risk, we identified 104 incident AD cases at follow-up. Main Outcome Measure: Diagnosis of AD by means of multistage assessment procedures. Results: Analyses of prevalent and incident AD yielded similar results. Use of vitamin E and C (ascorbic acid) supplements in combination was associated with reduced AD prevalence (adjusted odds ratio, 0.22; 95% confidence interval, 0.05-0.60) and incidence (adjusted hazard ratio, 0.36; 95% confidence interval, 0.09-0.99). A trend toward lower AD risk was also evident in users of vitamin E and multivitamins containing vitamin C, but we saw no evidence of a protective effect with use of vitamin E or vitamin C supplements alone, with multivitamins alone, or with vitamin B–complex supplements. Conclusions: Use of vitamin E and vitamin C supplements in combination is associated with reduced prevalence and incidence of AD. Antioxidant supplements merit further study as agents for the primary prevention of AD

Do Statins Reduce Risk of Incident Dementia and Alzheimer\u27s Disease? The Cache County Study

Background: Prior reports suggest reduced occurrence of dementia and Alzheimer disease (AD) in statin users, but, to our knowledge, no prospective studies relate statin use and dementia incidence. Objective: To examine the association of statin use with both prevalence and incidence of dementia and AD. Design: Cross-sectional studies of prevalence and incidence and a prospective study of incidence of dementia and AD among 5092 elderly residents (aged 65 years or older) of a single county. Participants were assessed at home in 1995-1997 and again in 1998-2000. A detailed visual inventory of medicines, including statins and other lipid-lowering agents, was collected at both assessments. Main Outcome Measures: Diagnosis of dementia and of AD. Results: From 4895 participants with data sufficient to determine cognitive status, we identified 355 cases of prevalent dementia (200 with AD) at initial assessment. Statin use was inversely associated with prevalence of dementia (adjusted odds ratio, 0.44; 95% confidence interval, 0.17-0.94). Three years later, we identified 185 cases of incident dementia (104 with AD) among 3308 survivors at risk. Statin use at baseline did not predict incidence of dementia or AD (adjusted hazard ratio for dementia, 1.19; 95% confidence interval, 0.53-2.34; adjusted hazard ratio for AD, 1.19; 95% confidence interval, 0.35-2.96), nor did statin use at follow-up (adjusted odds ratio for dementia, 1.04; 95% confidence interval, 0.56-1.81; adjusted odds ratio for AD, 0.85; 95% confidence interval, 0.32-1.88). Conclusions: Although statin use might be less frequent in those with prevalent dementia, we found no association between statin use and subsequent onset of dementia or AD. Further research is warranted before costly dementia prevention trials with statins are undertaken

Anti-Hypertensive Medication Use and Incident Alzheimer\u27s Disease. The Cache County Study

Background: Recent reports suggest that antihypertensive (AH) medications may reduce the risk of dementing illnesses. Objectives: To examine the relationship of AH medication use with incidence of Alzheimer disease (AD) among the elderly population (aged 65 years and older) of Cache County, Utah, and to examine whether the relationship varies with different classes of AH medications. Methods: After an initial (wave 1) multistage assessment (1995 through 1997) to identify prevalent cases of dementia, we used similar methods 3 years later (wave 2) to identify 104 incident cases of AD among the 3308 survivors. At the baseline assessment, we obtained a detailed drug inventory from the study participants. We carried out discrete time survival analyses to examine the association between the use of AH medications (including angiotensin converting enzyme inhibitors, beta-blockers, calcium channel blockers, and diuretics) at baseline with subsequent risk of AD. Results: Use of any AH medication at baseline was associated with lower incidence of AD (adjusted hazard ratio, 0.64; 95% confidence interval, 0.41-0.98). Examination of medication subclasses showed that use of diuretics (adjusted hazard ratio, 0.57; 95% confidence interval, 0.33-0.94), and specifically potassium-sparing diuretics (adjusted hazard ratio, 0.26; 95% confidence interval, 0.08-0.64), was associated with the greatest reduction in risk of AD. Corresponding analysis with a fully examined subsample controlling for blood pressure measurements did not substantially change our findings. Conclusions: These data suggest that AH medications, and specifically potassium-sparing diuretics, are associated with reduced incidence of AD. Because the latter association is a new finding, it requires confirmation in further study