Alzheimer's disease (AD) is a progressive disorder in which neurodegeneration begins decades before clinical symptoms appear. Detecting AD during this preclinical phase presents both the enormous challenge of identifying at-risk patients prior to symptom onset and the potential reward of treating patients early enough to prevent or slow disease progression. Given that a 5-year delay in the onset of the clinical manifestations of AD could result in almost a 50% reduction in disease prevalence, early detection of AD is a major focus of clinical research. Several objective, measurable indicators of preclinical and clinical characteristics of AD are currently available or in development. These biomarkers are promising because they promote identification of individuals at risk for AD onset and disease progression; diagnostic accuracy and treatment during the early stages of AD; and the development of disease-modifying therapies that may potentially slow or prevent disease progression during the preclinical phase of AD.

Treatment of attention-deficit/hyperactivity disorder (ADHD) may positively impact the neurobiology of adult patients with ADHD. Treatment may also minimize impairment from core symptoms and may alter the course of co-morbid disorders such as depression and substance use disorder. However, much of the information on stimulant use in adult ADHD comes from studies conducted in children, and it remains unclear whether there is a difference between children and adults when it comes to the side effects and tolerability of ADHD treatments. It is known that clinical presentation differs between adults and children, with adults demonstrating a higher percentage of mood disorders. Current treatments for adult ADHD include psychosocial therapies and pharmacologic therapies, the latter of which include the stimulants d-methylphenidate extended release (XR), OROS methylphenidate, lisdexamfetamine, and mixed amphetamine salts XR; and the nonstimulant atomoxetine, a selective norepinephrine reuptake inhibitor. There is need for additional study of treatment strategies for adult ADHD. Although all classes of ADHD medications are approved in adults, there are fewer approved formulations for adults than for children. Efficacy in adults is more subjective than in children, which may affect how efficacy rates for adult treatments are calculated. Adults also present a greater diversion risk than children. In addition, there are several new and emerging medication treatments worth considering.

This Expert Roundtable Supplement represents part 2 of a 3-part supplement series on adult ADHD led by Lenard A. Adler, MD. In this activity, Thomas J. Spencer, MD, discusses the neurobiology and genetics of adult ADHD; Mark A. Stein, PhD, discusses stimulant therapy; and Jeffrey H. Newcorn, MD, reviews nonstimulants and psychosocial treatments.

The 12-month and lifetime prevalences of bipolar I and II disorder in the United States are 2.0% and 3.3%, respectively. Similar to schizophrenia, bipolar disorder is also associated with premature and excess mortality, with an estimated loss of ∼15 years of life expectancy. Most of the excess mortality in individuals with mood disorders results from natural causes, not suicide. Again, similar to schizophrenia, the most common cause of death in patients with bipolar disorder is cardiovascular disease (CVD), which occurs approximately twice as often in this group as in the general population. Although the data are more limited than in schizophrenia, people with bipolar disorder are differentially affected by medical comorbidity. Bipolar disorder is associated with elevated risk of a wide variety of comorbid medical illnesses, including migraine, asthma, chronic bronchitis, hypertension, and gastric ulcer, which compound disability and increase the burden of the disease.

In discussions of diversion and misuse of medications in adult attention-deficit/hyperactivity disorder (ADHD), the word “misuse” is intentionally used. Abuse of a medication refers to excessive use of a drug to achieve a “high,” which may result in addiction to the medication and which causes dysfunction in a patient's life. However, misuse refers to usage of a medication without a prescription or for reasons other than that which it was prescribed. Diversion refers to the diverting of legally prescribed medication into illegal use by other than the patient. Sahakian and Morein-Zamir recently discussed the use of cognitive-enhancing drugs by individuals with a variety of disorders as well as off-label and non-prescription use by the general public. In addition to inappropriate use of medications, patients with ADHD often turn to other substances that are detrimental to their health, such as nicotine.

There is a complex overlap between major depressive disorder (MDD) and attention-deficit/hyperactivity disorder (ADHD). The different therapeutic options for adult ADHD mirror those used for children with ADHD. Both stimulant and nonstimulant medications are used to treat the disorder.

Full remission, defined as the absence of all significant symptoms of depression over at least 6 months, is the ultimate goal of antidepressant therapy. Remission takes time and studies have shown that remission rates continue to rise for at least 3 months after initial improvement. Depression is a recurrent condition with a cumulative probability of recurrence of 40% over 2 years and 70% over 5 years after the first depressive episode. In addition the risk of recurrence increases with each new depressive episode. Continuing antidepressant treatment beyond the acute response significantly decreases the risk of recurrence. A double-blind study with the serotonin norepinephrine reuptake inhibitor milnacipran, for example, has shown that patients in remission following treatment with milnacipran who continued the active treatment for a further 12 months had significantly less relapse (P<.05) than those switched to placebo. In spite of the importance of maintaining antidepressant therapy, many patients do not continue treatment. Among the principal reasons for this are side effects and worries of psychological or physical dependence. To reduce the risk of relapse, treatment with effective, well-tolerated antidepressants with few withdrawal effects should be pursued for at least 6 months and possibly longer in patients already experiencing relapse.

While insomnia is common among men and women and across all age groups, older adults and women experience markedly increased risk for this disorder. Insomnia complaints in adults ≥65 years of age are very common. Foley and colleagues demonstrated in a study of 9,282 older adults (mean age of 74) an insomnia prevalence rate of ∼60%.

Approximately 57% of older adults have sleep complaints (Slide 1). Most of these are associated with comorbid conditions including depressed mood, respiratory problems, or poor physical health. The healthiest members of this population have far fewer sleep complaints.

The diagnosis of dementia has always represented both a challenging and hastened end to life. William, born in 1924, grew up on a farm, served in World War II, and became a successful restaurateur. His dementia began at 57 years of age and lasted 9 years. By year 3 he could no longer be managed at home and was placed in a nursing home. By year 5, he no longer knew his children, and at year 6, he could no longer speak. William's family described his eventual passing as a blessing, saying that he had been released from a terrible prison. Although the painful reality of this disorder continues, there has been significant progress in Alzheimer's disease treatment and now, optimism about the future of Alzheimer's disease management.

Parkinson's disease is a progressive neurodegenerative disorder with prominent motor features. The cardinal motor signs, bradykinesia, rigidity, and tremor, are treated effectively by dopaminergic therapies. Levodopa is standard, and often initial, therapy for patients with this condition. However, with continued treatment, and as the disease progresses, the response to oral dopaminergic drugs becomes unstable and motor fluctuations emerge, including off periods (when medication effects wear off) and dyskinesia (dystonic or choreatic movements) (Slide 1). Risk factors for motor complications include younger age at disease onset, longer disease duration, higher levodopa dosage, and more severe motor symptoms.