Alzheimer's disease is the leading cause of dementia. However, neither Alzheimer's disease nor Alzheimer's dementia are an inevitable consequence of aging. This review provides an overview of the issues involved in a diagnosis of Alzheimer's disease before an individual meets the criteria for Alzheimer's dementia. It examines how Alzheimer's disease diagnosis rates can be improved, the implications of an early diagnosis for the individual, carer and society, and the importance of risk reduction to prevent or delay progression. Although no disease-modifying agents capable of reversing the initial pathological changes are currently available, it may be possible to prevent or delay the development of dementia in a proportion of the population by modifying exposure to common risk factors. In other individuals, diagnosing the disease or risk of disease early is still valuable so that the individual and their carers have time to make choices and plan for the future, and to allow access to treatments that can help manage symptoms. Primary healthcare professionals play a pivotal role in recognising individuals at risk, recommending lifestyle changes in mid-adult life that can prevent or slow down the disease, and in timely diagnosis. Early intervention is the optimal strategy, because the patient's level of function is preserved for longer.

Impaired sexual function is associated with major depressive disorder in the untreated state and is often more prevalent during antidepressant therapy, which frequently results in poor treatment compliance. In this double-blind, multicenter study, the effects of agomelatine (an MT1 and MT2 agonist and 5HT-2C antagonist) and venlafaxine XR on sexual function were compared using the Sex Effects Scale in depressed patients. A total of 276 male and female patients received either agomelatine (50 mg) or venlafaxine XR (titrated to a target dose of 150 mg/d) for 12 weeks. Those who were sexually active at baseline (n = 193) and those who, in addition, achieved remission (n = 111) were defined a priori for analyses of change in sexual function. Treatment-emergent sexual dysfunction was significantly less prevalent among patients who received agomelatine, and venlafaxine XR was associated with significantly greater deterioration on the Sex Effects Scale domains of desire and orgasm. Both treatments resulted in equivalently high rates of remission (agomelatine, 73%; venlafaxine XR, 66.9%), although fewer patients in the agomelatine group discontinued treatment because of adverse events (agomelatine, 2.2%, vs venlafaxine XR, 8.6%). Agomelatine seems to be an efficacious antidepressant with a superior sexual side effect profile compared with venlafaxine XR, although superiority to placebo was not evaluated in this trial.

Given considerable variation in diagnostic and therapeutic practice, there is a need for national guidance on the use of neuroimaging, fluid biomarkers, cognitive testing, follow-up and diagnostic terminology in mild cognitive impairment (MCI). MCI is a heterogenous clinical syndrome reflecting a change in cognitive function and deficits on neuropsychological testing but relatively intact activities of daily living. MCI is a risk state for further cognitive and functional decline with 5–15% of people developing dementia per year. However, ~50% remain stable at 5 years and in a minority, symptoms resolve over time. There is considerable debate about whether MCI is a useful clinical diagnosis, or whether the use of the term prevents proper inquiry (by history, examination and investigations) into underlying causes of cognitive symptoms, which can include prodromal neurodegenerative disease, other physical or psychiatric illness, or combinations thereof. Cognitive testing, neuroimaging and fluid biomarkers can improve the sensitivity and specificity of aetiological diagnosis, with growing evidence that these may also help guide prognosis. Diagnostic criteria allow for a diagnosis of Alzheimer’s disease to be made where MCI is accompanied by appropriate biomarker changes, but in practice, such biomarkers are not available in routine clinical practice in the UK. This would change if disease-modifying therapies became available and required a definitive diagnosis but would present major challenges to the National Health Service and similar health systems. Significantly increased investment would be required in training, infrastructure and provision of fluid biomarkers and neuroimaging. Statistical techniques combining markers may provide greater sensitivity and specificity than any single disease marker but their practical usefulness will depend on large-scale studies to ensure ecological validity and that multiple measures, e.g. both cognitive tests and biomarkers, are widely available for clinical use. To perform such large studies, we must increase research participation amongst those with MCI.

Background: Psychotic symptoms are common in Alzheimer's disease (AD) and related neurodegenerative disorders and are associated with more rapid disease progression and increased mortality. It is unclear to what degree existing criteria are utilized in clinical research and practice. Objective: To establish research criteria for the diagnosis of psychosis in AD. Methods: The International Society to Advance Alzheimer's Research and Treatment (ISTAART) Neuropsychiatric Symptoms (NPS) Professional Interest Area (PIA) psychosis subgroup reviewed existing criteria for psychosis in AD and related dementias. Through a series of in person and on-line meetings, a priority checklist was devised to capture features necessary for current research and clinical needs. PubMed, Medline and other relevant databases were searched for relevant criteria. Results: Consensus identified three sets of criteria suitable for review including those of Jeste and Finkel, Lyketsos, and the Diagnostic and Statistical Manual for Mental Disorders, 5th edition. It was concluded that existing criteria could be augmented by including a more specific differentiation between delusions and hallucinations, address overlap with related conditions (agitation in particular), adding the possibility of symptoms emerging in the preclinical and prodromal phases, and building on developing research in disease biomarkers. Conclusion: We propose criteria, developed to improve phenotypic classification of psychosis in AD, and advance the research agenda in the field to improve epidemiological, biomarker, and genetics research in the field. These criteria serve as a complement to the International Psychogeriatric Association criteria for psychosis in neurocognitive disorders.

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Nutritional factors can influence the risk of developing Alzheimer’s disease (AD) and its rate of progression, and there is, therefore, increasing interest in nutrition as a modifiable risk factor for the disease. Synaptic loss is an important feature of early AD, and the formation of new synapses is dependent on key nutritional elements that are known to be deficient in patients with AD. The daily medical food, Souvenaid, contains Fortasyn Connect, a multinutrient combination developed to specifically address these deficiencies, comprising docosahexaenoic acid, eicosapentaenoic acid, uridine monophosphate, choline, phospholipids, selenium, folic acid, and vitamins B12, B6, C, and E. Although yielding heterogeneous findings, clinical studies of Fortasyn Connect provide preliminary evidence of clinically relevant benefits on cognitive outcomes in prodromal and early AD. The LipiDiDiet trial investigated the effects of Fortasyn Connect on cognition and related measures in prodromal AD, and is the first randomized, controlled, double-blind, multicenter trial study of a non-pharmacological intervention in this setting. The primary efficacy endpoint was change over 24 months in a composite score of cognitive performance using a neuropsychological test battery. Fortasyn Connect had no significant effect on this endpoint, but demonstrated a significant benefit on secondary endpoints, including domains of cognition affected by AD (attention, memory, executive function) and hippocampal atrophy, suggesting a potential benefit on disease progression. Other studies have demonstrated benefits for Fortasyn Connect on nutritional markers and levels of plasma homocysteine. Taken together, current evidence indicates that Fortasyn Connect may show benefit on domains of cognition affected by AD and nutritional measures that influence risk factors for its progression; that it has greater potential for benefit earlier rather than later in the disease; and that it is safe and well tolerated, alone or in combination with AD medications. Further research into its potential role in AD management is therefore warranted.