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In mild cognitive impairment (MCI) due to Alzheimer disease (AD), also known as prodromal AD, there is evidence for a pathologic shortage of uridine, choline, and docosahexaenoic acid [DHA]), which are key nutrients needed by the brain. Preclinical and clinical evidence shows the importance of nutrient bioavailability to support the development and maintenance of brain structure and function in MCI and AD. Availability of key nutrients is limited in MCI, creating a distinct nutritional need for uridine, choline, and DHA. Evidence suggests that metabolic derangements associated with ageing and disease-related pathology can affect the body’s ability to generate and utilize nutrients. This is reflected in lower levels of nutrients measured in the plasma and brains of individuals with MCI and AD dementia, and progressive loss of cognitive performance. The uridine shortage cannot be corrected by normal diet, making uridine a conditionally essential nutrient in affected individuals. It is also challenging to correct the choline shortfall through diet alone, because brain uptake from the plasma significantly decreases with ageing. There is no strong evidence to support the use of single-agent supplements in the management of MCI due to AD. As uridine and choline work synergistically with DHA to increase phosphatidylcholine formation, there is a compelling rationale to combine these nutrients. A multinutrient enriched with uridine, choline, and DHA developed to support brain function has been evaluated in randomized controlled trials covering a spectrum of dementia from MCI to moderate AD. A randomized controlled trial in subjects with prodromal AD showed that multinutrient intervention slowed brain atrophy and improved some measures of cognition. Based on the available clinical evidence, nutritional intervention should be considered as a part of the approach to the management of individuals with MCI due to AD, including adherence to a healthy, balanced diet, and consideration of evidence-based multinutrient supplements.

New super-sensitive biomarker assay platforms for measuring Alzheimer’s disease (AD) core pathological markers in plasma have recently been developed and tested. Research findings from these technologies offer promising evidence for identifying the earliest stages of AD and correlating them with brain pathological progression. Here, we review findings using immunomagnetic reduction, one of these ultrasensitive technologies. The principles, technology and assays developed, along with selected published findings will be discussed. The major findings from this technology were significant increases of amyloid beta (Aβ) 42 and total tau (t-tau) levels in subjects clinically diagnosed with early AD when compared with cognitively normal control (NC) subjects. The composite marker of the product of Aβ42 and t-tau discriminated subjects with early AD from NC subjects with high accuracy. The potential of this technology for the purpose of early or preclinical disease stage detection has yet to be explored in subjects who have also been assessed with brain imaging and cerebrospinal fluid AD core biomarker measurements.

Introduction Polypharmacy is a growing problem in the United States. The use of multiple medications increases the likelihood that a patient will experience potential drug interactions and adverse drug reactions (ADRs). Those individuals with dementia or Alzheimer’s disease (AD) are at greater risk, due to age, comorbidities, and an increased likelihood of being on a greater number of neuroactive medications. Methods uMETHOD Health (uMH) has developed a precision medicine platform to address dementia and mild AD through the creation of personalized, multidomain treatment plans. Many interactions and ADRs may be observed, such as drug–drug interactions (DDIs), drug–gene interactions (DGIs), anticholinergic cognitive burden (ACB), and depression-inducing drugs (DIDs). uMH’s algorithms can parse these interactions, rate them based on input from open-source databases, and then record all these interactions in a generated treatment plan. A total of 295 individuals aged 65 and older were included in this analysis. Results Of 295 individuals, 97.59% were on at least one medication, with an overall mean of 11.5 medications per person; 83.66% were on five or more medications. A total of 102 DGIs, 3642 DDIs, and one high-priority DDI were found in this population. There was a significant increase in the number of DDIs as medications per person increased (P value

Alzheimer's disease is an important condition with a considerable and unmet disease burden in large need of continued research and more treatment options. The 5HT6 antagonists are a new class of medications to be offered. Because they are pro-cholinergic, these medications are to be used as adjuncts to acetylcholinesterase inhibitors (such as donepezil), further increasing acetylcholine in the central nervous system (CNS). Early trials of the 5HT6 antagonists showed improvements in cognition and activities of daily living when used as adjuncts to current therapies for Alzheimer's dementia. However, recent phase III trials have failed to show a statistically significant improvement in cognitive function. This article will provide a comprehensive review of 5HT6 antagonists in drug development, including some that have been recently discontinued. We will discuss both the successes and failures of this drug class and provide rationale for their continued research and development.

Alzheimer’s disease (AD) is a devastating neurodegenerative disorder affecting the elderly. Current clinical diagnostic tools are often ineffective in accurately diagnosing AD. However, new advances in diagnostic imaging, particularly positron emission tomography (PET) amyloid imaging, have shown increased sensitivity and specificity, as well as high inter-reader agreement. The most commonly studied tracer, PiB-C11, has shown high affinity binding to amyloid, but is limited in its use outside of research due to its short half-life. Instead, development of other PET ligands with increased half-life, such as fluorine-18-labeled (18F) tracers, allows for more widespread use of PET in clinical settings. In particular, recent phase II and III trials of 18F-florbetaben have demonstrated the high accuracy of this PET tracer in identifying amyloid accumulation. This paper will examine the techniques of amyloid imaging, focusing particularly on the recently approved 18F-florbetaben. Electronic supplementary material The online version of this article (doi:10.1007/s40120-014-0022-9) contains supplementary material, which is available to authorized users.