Almost 36 million people will have dementia in 2010—an alarming figure set to double every 20 years with the “greying” of the world population. Alzheimer's disease (AD) and dementia have enormous financial and social impacts on society. Prevention or illness delay of even a small percentage of cases would provide significant cost benefits for health-care systems. This review considers the rationale for a combined B-vitamin and antioxidant supplement (Cerefolin NAC) in treating and slowing AD-related cognitive decline.

Vitamin B12 and folate deficiencies are associated with various cognitive disorders, including dementia. In the 1980s, plasma total homocysteine (tHcy) assays were introduced to assist in diagnosing these deficiencies. Hey is derived from dietary methionine. Cells re-methylate Hey to methionine using B12-dependent methionine synthase; 5-methyltetrahydrofolate (5-MTHF) acts as a methyl donor (Figure 1A). Alternatively, Hey is converted to cystathionine, and ultimately cysteine, by B6-dependent cystathionine β-synthase. Blood Hey levels rise in B6, B6, and folate deficiencies.Higher levels are also associated with aging, smoking, male gender, renal impairment, and drugs including methotrexate, metformin, and levodopa.

Using tHcy as a marker, B vitamin deficiencies were found to be highly prevalent in the elderly. This led to speculation that elevated blood Hey, hyperhomocysteinemia, might occur commonly in dementias, including AD. Hyperhomocysteinemia implies impaired meth-ylation reactions (hypomethylation), with predictable adverse effects for neurotransmitter synthesis and AD neuropathology. Hey is also associated with vascular disease, itself a risk factor for dementia.

Evidence for the “homocysteine hypothesis of dementia” came with reports of hyperhomocysteinemia in patients with clinically and pathologically confirmed AD. Raised blood levels were also observed in mild cognitive impairment (MCI) and vascular dementia. Although elevated Hey could be a consequence of, or coincidental with, dementia hyperhomocysteinemia, it is now recognised to be associated with an increased risk for both cognitive decline and incident dementia.

This is the second published case report of Lleuprolide acetate for depot suspension (LD)-induced mania. Both reports detail a patient with a prior psychiatric history of both depressive and hypomanic episodes. While depression is a predictable and documented side effect of LD and menopause (especially in those with a previoushistory of symptoms), manic reactions are rare and unexplained. Possible causative mechanismsbehind the LD-induced manic episodes are discussed, and we suggest that patients with a single previous hypomanic episode are at risk for LD-induced mania.

A 64-year-old man had a first generalized seizure. He was seen in an emergency room where magnetic resonance imaging revealed a right parietal meningioma with a diameter of 2.5 cm. He was seen by the neurosurgery team and a craniotomy was performed. He was discharged from the hospital on phenytoin. Three weeks later he reported drowsiness and unsteadiness to his neurologist. In addition, he described episodes of transient sensory disturbance in his left arm, sometimes with twitching movements of the left hand and wrist. These episodes could last ≤3 minutes, and his hand and arm would be weak afterward for several hours. A phenytoin level was measured at 17. Lamotrigine was added to his regimen, and on 400 mg/day the lamotrigine level was 3.8. The dose was increased gradually to 400 mg BID and seizures stopped. Two hours after each dose, however, the patient would become dizzy, nauseated, and encephalopathic for a period of 60–90 minutes.

The patient presented with a convulsive seizure due to a meningioma and developed simple partial sensorymotor seizures arising in the region of the meningioma after its resection. The seizures persisted with phenytoin at a moderately high serum level but responded to lamotrigine as a second agent at just above the maximum tolerated dose. This case illustrates a common course of events for otherwise healthy adults who have seizures due to structural brain disease and are placed on phenytoin and lamotrigine.

Before reviewing the differential diagnosis of bipolar disorder, it is important to understand the epidemiology, incident, and prevalence of the disorder as well as to divide it by type: type I, type II, or the phenomenon of not otherwise specified, which is defined as subthreshold mania or hypomania. Subthreshold mania or hypomania entails fewer than the requisite number of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition symptoms of mania or hypomania, or an insufficient duration of time with which to make a diagnosis of a syndrome of mania or hypomania. Currently, the most reliable epidemiology of prevalence rates were reported in a replication study of 9,282 respondents to the National Comorbidity Survey conducted by Merikangas and colleagues.

Those data show there is a lifetime prevalence rate of bipolar I disorder of 1 % and bipolar II disorder of 1.1%. In this study, not otherwise specified was labeled subthreshold bipolar disorder as the illness duration was not long enough or the number of symptoms was not extensive enough to constitute syndromal mania or hypomania. This type had a prevalence rate of 2.4%, for a total lifetime prevalence of ~4.4%. This rate is somewhat higher than has been described in the past, but included the subdivision that researchers believe comprises the bipolar spectrum.

There has been much underdiagnosis or lack of diagnostic accuracy of bipolar disorder, with relative overdiagnosis of major depressive disorder, which historically has been well documented. However, in the last 10 years, there has been a substantial increase in the making of diagnoses of bipolar disorder in various clinical settings. One dataset examined ambulatory medical care survey data and found that among adults over an ~10-year period, there was approximately a doubling in the incidence of diagnosing bipolar disorder of any type (Slide 1).

Simone is a 64-year-old African American female with a 25-year history of schizophrenia who had been hospitalized ∼10 times. Simone's last psychiatric hospitalization occurred 2 years prior to this presentation. She had been living in a supervised residence facility in a rural community with other patients and was generally adherent to her medications with encouragement by staff at her residence. Her psychotic symptoms had improved but had not disappeared. She continued to have persistent delusions that the Federal Bureau of Investigation was keeping her under surveillance because of information she supposedly had about national security. She continued to smoke 1 pack of cigarettes/day despite being told that she was developing chronic obstructive pulmonary disease. She stopped abusing alcohol, principally because of a lack of funds and lack of access to a liquor store. Simone was obese, with a body mass index (BMI) of 30 kg/m2. She was hypertensive, with a blood pressure of 140 over 95, and had mild abnormalities in her metabolic variables. She enjoyed fatty foods and never refused a meal.

Simone's case is not an unusual presentation for someone with schizophrenia. Psychiatric and somatic comorbidities in patients with schizophrenia are quite common. There is justifiable concern regarding long-term impact of treatments on metabolic variables, and metabolic comorbidities are often encountered.

For most patients with major depressive disorder (MDD) the first-line treatment is one of the selective serotonin reuptake inhibitors (SSRIs). However, some practitioners prefer to utilize a serotonin norepinephrine reuptake inhibitor (SNRI) or the norepinephrine-dopamine reuptake inhibitor bupropion as their first-line antidepressant treatments (Slide 1). Differences of opinion regarding first, second, or third choice of antidepressant often stem from regional practices or individual training.

A basic standard of practice in MDD treatment is to initiate monotherapy trials with several first-line choices of antidepressants before moving on to alternate strategies. This basic strategy was evaluated in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. Only approximately one third of the patients remitted after being treated with the study's first-line treatment, a 12-week trial of citalopram in doses up to 60 mg/day. As in other contemporary treatment studies, remission was defined as virtually complete relief of depressive symptoms. This is defined as a Hamilton Rating Scale for Depression score of ≤7 or a score of ≤5 on the self-report version of the Quick Inventory of Depressive Symptomatology.

For those who did not obtain an adequate response to the initial course of citalopram therapy, the STAR*D study compared several alternate treatments, including switching to another antidepressant, adjunctive therapy with another type of medication (ie, a medication that is not an antidepressant), or combination treatment (ie, adding another antidepressant). At the end of four sequential treatment trials, only approximately two thirds of the patients remitted. Of those, 40% to 70% relapsed within the next year despite continued therapy.

Clinicians treating patients with first-episode (FE) schizophrenia can draw upon the vast literature on the treatment of patients with multiple-episode schizophrenia. Studies with multi-episode patients, however, may not fully generalize to the treatment of FE patients. Studies with multi-episode patients typically recruit from hospitals or other acute care units, settings where patients usually have been either non-responsive or non-adherent to previous treatment, or mixtures of both. Studies of multi-episode patients therefore tend to include patients who are not fully responsive to treatment. Without the filter of prior treatment history, FE compared with multi-episode patients may show a broader range of treatment patterns, ranging from extremely good to very poor. Further, studies of FE patients may be very instructive about side effects, as the confounding effect of prior medication use is particularly important with side effects. Finally, data suggest that much of the deterioration (eg, more severe negative symptoms) associated with schizophrenia may occur during the 5 years following illness onset. Providing patients with better treatment at illness onset offers the hope of improving their long-term outcome.

FE studies do have limitations. Relatively few new cases of schizophrenia occur each year. The typically chronic course of schizophrenia results in a large number of patients with multi-episode schizophrenia for every FE patient at any one time. Recruitment for studies of FE schizophrenia compared with those of multi-episode schizophrenia is often more difficult given the smaller number of available patients. We systematically know less about the treatment of FE patients than we do about the treatment of multi-episode patients.