American Journal of Alzheimer's Disease & Other Dementias®

Recent clinical trials and critical reviews of Alzheimer's disease (AD) research discourage already relatively sparing clinical uses of cholinesterase inhibitors (ChEIs) considering the prevalence of AD. As evidence against use of this class of drugs, detractors cite critical reviews of ChEls and lack of long-term health benefits found in one long-term clinical trial. This paper describes the use of standard error of measurement to allow investigators to design clinical trials that address these issues. The new clinical trial procedures afford sufficient precision for two purposes. First, practitioners can assess individual patients with precision and certainty in their observations. Second, clinical trial researchers can study how short-term drug effects on individual patients predict long-term benefits from continued treatment. With these more clinically informative clinical trial designs, investigators would be able to avoid uncertainties currently raised by conflicts between short-and long-term AD clinical trials.

Dementia patients' caregivers often provide information about patients' daily functioning, but little is known about factors influencing caregivers' perceptions. Baseline data from an intervention trial were used to compare caregiver estimates of dementia patients' performance with their actual performance of instrumental activities of daily living (IADLs) and to assess relationships between measures of caregiver responses to caregiving, self-perceived sense of self-efficacy, and depression. We also assessed patient cognition, overall function and behavioral disturbance, and caregivers' perceptions of their patients' behavior as manipulative or deliberate. Disparities between these estimates and actual patient performance on structured IADL tasks were unrelated to any caregiver, patient, or relationship factor that we measured.

Background: Although the significance of apolipoprotein E4 (Apo E4) in Alzheimer's disease (AD) has been well established in Caucasian populations, its role in determining the rate of cognitive decline in other ethnic groups has yet to be determined This study examined the two-year progression of cognitive decline and its association with Apo E4 allelic status in a group of Chinese elderly subjects with AD.

Method: One hundred andfour Chinese subjects with mild and moderate AD as assessed by the Clinical Dementia Rating (CDR 1 and 2) were followed up at a mean (SD) duration of 22.53 (5.21) months. The rate of cognitive decline and its association with Apo E4 allelic status was evaluated.

Results: At follow-up, 74 (73 percent) subjects were reassessed. Forty-nine remained stable at the same CDR and 25 had deteriorated The mean (SD) deterioration in the Mini-Mental State Examination (MMSE) was 2.52 (4.38) and in the Mattis Dementia Rating Scale (DRS) was 9.03 (14.98) (paired t-test, p < 0. 001). There was no significant difference in the baseline MMSE and DRS scores between the “stable,” “deteriorated,” or “deceased” groups. Mildly demented subjects with the Apo E4 allele were more likely to have deteriorated to a more severe CDR than subjects without the Apo E4 allele (Pearson χ² = 5.72, df 1, p = 0.017, Odds ratio = 6.3, CI 1.3 to 30.53).

Conclusion: The presence of the Apo E4 allele may influence the rate ofcognitive deterioration, particularly in subjects with mildAD.

The behavioral and psychological symptoms of dementia (BPSD), such as psychosis, agitation, or aggression have a considerable negative impact on the quality of life of both patients and their caregivers. Multiple studies have demonstrated that atypical antipsychotics are efficacious in the treatment of the aggressive and psychotic symptom clusters, and here we review their use in this indication. Because of the safety concerns associated with the use of atypical antipsychotics in this population, these drugs must be usedjudiciously. For patients with severe BPSD such as psychosis, agitation, or aggression, for whom there are few options, atypical antipsychotics, particularly risperidone and olanzapine, should be considered.

The Mini-Mental State Examination (MMSE) is a commonly used clinical toolfor evaluating the cognitive aspects of mental function. In this study, 40 consecutive patients presenting to a memory disorder clinic and their caregivers were evaluated for coaching of the patient with respect to MMSE content over the 24 hours prior to clinical evaluation. Caregivers completed a questionnaire concerning MMSE practice sessions with the patient prior to the physician encounter; then, the patients were asked to spell the word “WORM” backwards instead of “WORLD” during the MMSE test. Some or all of the MMSE content was reviewed with the patient prior to the interview by 42.5 percent of the caregivers, 17.5 percent ofpatients spelled or attempted to spell “WORLD” backwards instead of “WORM” These results demonstrate that coaching of patients prior to administration of the MMSE is not uncommon, and that this needs to be taken into consideration when forming therapeutic decisions based on MMSE results.

Alzheimer s disease (AD) is characterized by profound memory loss sufficient to interfere with social and occupationalfunctioning. It is the most common form of dementia, affecting more than 20 million people worldwide. AD is characterized by an insidious loss of memory, associated functional decline, and behavioral disturbances. Patients may live for more than a decade after they are diagnosed with AD, making it the leading cause of disability in the elderly. The incidence of AD rangesfrom I to 4 percent of the population per year, rising from its lowest level at ages 65 to 70 years to rates that may approach 6 percent for those over the age of 85 years. The first neurotransmitter defect discovered in AD involved acetylcholine (A Ch). As cholinergic function is requiredfor short-term memory, the cholinergic deficit in AD was also believed to be responsible for much of the short-term memory deficit. Clinical drug trials in patients with AD have focused on drugs that augment levels of A Ch in the brain to compensate for the loss of cholinergic function. These drugs have included ACh precursors, muscarinic agonists, nicotinic agonists, and acetylcholinesterase inhibitors. The most highly developed and successful approaches to date have employed acetylcholinestrase inhibition. Although some Food and Drug Administration-approved drugs are available for the treatment ofAlzheimer's disease, the outcomes are often unsatisfactory, and there is a place for alternative medicine, in particular, herbal medicine. This paper reviews the clinical effects of a number of commonly used types of herbal medicines for the treatment ofAD.

Early recognition and treatment initiation are pivotal in managing Alzheimer k disease (AD). Once a diagnosis of AD is made, a treatment plan is developed and should include treatment initiation with cholinesterase inhibitors (ChEfs) to improve cognition, management of comorbid conditions, and treat behavioral symptoms. Caregiver compliance is integral to AD treatment success. The purpose of this report is to present two real case studies of “suspected” AD or related dementia and stress the significance of early and accurate diagnosis in disease management. In case 1, a caregiver reports gradual but progressive loss of memory, and the patient himself complains of memory impairment. Neuroimaging analysis confirms “typical” AD. In case 2, initiation of ChEI therapy is followed by substantial clinical improvement in the face of a complex medical picture, and neuroimaging revealing more neurodegenerative changes than could be accountedfor by “pure” AD.

In Alzheimer s disease (AD), the major components of senile plaques and neurofibrillary tangles, amyloid-β and tau, respectively, are thought by many to play a key role in disease initiation and progression. However, herein we propose that rather than being initiators of disease pathogenesis, the lesions that characterize AD, senile plaques and neurofibrillary pathology, occur consequent to oxidative stress and, importantly, function as a primary line of antioxidant defense. Importantly, this paradigm shift in thinking about the role of lesions in disease also provides an explanation for the appearance of both amyloid-β and tau in control individuals given the increased levels of oxidative stress associated with the aged brain. In AD, oxidative stress is not only high but chronic and is superimposed upon an age-related vulnerable environment. Therefore, one would predict, successfully, an increased lesion load in patients with AD above and beyond that seen in normal aging. The notion that amyloid-β and tau accumulations indicate adaptation and, likely, physiological processes sheds light on the pathological expression of disease and calls into question the rationale of current therapeutic efforts targeted toward lesion removal.

The purpose of this study was to determine whether a family history of dementia in afirst-degree relative influenced the progression of Alzheimer s disease (AD) after two years offollow-up. Patients were recruited in the REAL.FR (Reseau sur la Maladie d'Alzheimer Franqais) study and underwent behavioral, global, nutritional, and medical evaluation with assessment ofcognitivefunction and independence every six months. At inclusion, 113 patients reported a family history of dementia, and 358 patients had no family history of dementia. There was no statistical difference for any factors between the two groups at baseline. After two years offollow-up, a similar percentage of patients were still followed in each group, and although most parameters showed significant deterioration, there was no difference between the two groups, indicating that a family history of dementia does not appear to influence the progression of AD.