Alzheimer Disease & Dementia

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A discovery about the brain protein KIBRA, commonly found in the kidneys and brain, could lead to future treatments for Alzheimer disease (AD). Investigators at the Translational Genomics Research Institute (TGen), lead by Corneveaux and Liang, in Phoenix found that the risk for AD is 25% lower in persons who carry the memory-enhancing KIBRA gene.1 This fi nding indicates that there might be a link between KIBRA and some of the proteins with which it interacts.

The use of antipsychotics to quiet agitated older adults with dementia has come under increasing fire. After a Canadian study demonstrated an increased risk of adverse events or death with these agents,1 the FDA expanded its earlier warning to physicians.

A variety of conditions may account for the sleep difficulties experienced by many older adults, including specific sleep disorders, circadian rhythm disturbances, and medical and psychiatric comorbidities.

On a hypothetical morning, you've arrived early at your office to answer e-mails and respond to prescription requests without interruptions. The following voice mail, left for you much earlier that day, awaits your attention: "Doctor, I need to discuss my mother's behavior with you. The medications she's taking might be calming her down during the days, but she's not okay at night."

Almost 3 years after the FDA warned of increased mortality in elderly patients who received atypical antipsychotics off-label for neuropsychiatric syndromes of dementia, no medication has been approved as safe and effective for this increasingly challenging problem. Recent publications, however, including a white paper from the American College of Neuropsychopharmacology (ACNP), indicate that clinical investigators are wrestling with the dilemma and considering potential alternatives to antipsychotics.

A recent 4-year study linked apathy to a hastened decline in persons with Alzheimer disease (AD). Another recent study found that persons with mild cognitive impairment (MCI) were more likely to convert to AD a year later if they also had apathy.

Short of mass screening of the elderly using a neuropsychological test or some yet-to-be-determined biomarker, persons with cognitive disorders come to the attention of the health care system only when symptoms are recognized. Occasionally, physicians identify cognitive deficit on routine examination or when they notice patients having trouble following instructions (eg, taking medications properly)

Conventional antipsychotic drugs such as haloperidol have been supplanted by newer, atypical antipsychotics (risperidone [Risperdal], olanzapine [Zyprexa], quetiapine [Seroquel], ziprasidone [Geodon], aripiprazole [Abilify]), although no medication has an FDA indication for the treatment of behavioral symptoms in patients with dementia

In many ways, the frustration experienced bypatients struggling with mild cognitive impairment(MCI) is matched by the frustration ofclinicians facing the challenge of managing thisheterogeneous condition. The prognosis can bevariable, and no proven therapies exist.

Defined as a clinical syndrome involving progressive deterioration in multiple areas of cognitive functioning, dementia is a major cause of disability, institutionalization, and increased mortality among the elderly. Although it can occur in younger persons too, dementia is typically associated with aging. It is often seen as a disease that cannot be prevented or cured. However, there is increasing evidence that some types of dementia can be successfully treated or even reversed.

In patients with dementia who are physically aggressive and dangerous to themselves or others, the use of intramuscular haloperidol or lorazepam may be appropriate. Because haloperidol causes less drowsiness and cognitive impairment than lorazepam, it is preferred in patients with dementia and delirium. The usual dose of haloperidol for elderly patients with dementia is 0.5 to 1 mg; this dose can be repeated every 25 to 30 minutes until the patient is no longer dangerous to self or others. If benzodiazepine or alcohol withdrawal is suspected, lorazepam is the preferred medication. Physical restraints may be appropriate until the medication takes effect.

Increased plasma cortisol levels (correlated with increased hypothalamic-pituitary-adrenal axis activity) may be associated with more rapid disease progression in Alzheimer-type dementia (AD). In a study conducted at the Washington University School of Medicine in St Louis, Dr John Csernansky and colleagues assessed 33 patients with very mild or mild AD and 21 persons without AD annually for up to 4 years, using the Clinical Dementia Rating Scale and various neuropsychological tests. Plasma was obtained from each patient and assessed for cortisol level.

Given the lack of a good evidence base for pharmacological treatment of neuropsychiatric symptoms of dementia, are there any effective treatments for such problems as agitation, aggression, delusions, hallucinations, repetitive vocalizations, and wandering? A recent review suggests that nondrug interventions that address behavioral issues and unmet needs may be helpful, as may caregiving interventions and the use of bright light therapy.

Theories about the causes of Parkinson disease (PD) are as tangled as the neurofilament proteins of Lewy bodies. However, investigators are teasing out threads of evidence that increasingly implicate environmental factors--perhaps aided and abetted by genetics--as contributors to this common neurodegenerative disorder.