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PHILADELPHIA – Nearly half of dementia cases worldwide could theoretically be prevented or delayed by eliminating 14 modifiable risk factors during an individual's lifetime, a report from the Lancet Commission on dementia prevention, intervention, and care. The report adds two new modifiable risk factors for dementia — high cholesterol and vision loss — to the 12 risk factors identified in the 2020 Lancet Commission report, which were linked to about 40% of all dementia cases. The original Lancet Commission report, published in 2017, identified nine modifiable risk factors that were estimated to be responsible for one third of dementia cases. "Our new report reveals that there is much more that can and should be done to reduce the risk of dementia. It's never too early or too late to act, with opportunities to make an impact at any stage of life," lead author Gill Livingston, MD, from University College London, UK, said in a statement. The 57-page report was published online July 31 in The Lancet Neurology to coincide with its presentation at the Alzheimer's Association International Conference 2024. 'Compelling' New Evidence The 12 risk factors cited in the 2020 report are lower levels of education, hearing loss, hypertension, smoking, obesity, depression, physical inactivity, diabetes, excessive alcohol consumption, traumatic brain injury (TBI), air pollution, and social isolation. According to the authors of the current report, there is "new compelling evidence" that untreated vision loss and elevated low-density lipoprotein (LDL) cholesterol are also risk factors for dementia. These two added risk factors are associated with 9% of all dementia cases — with an estimated 7% of cases due to high LDL cholesterol from about age 40 years, and 2% of cases due to untreated vision loss in later life, the authors said. Out of all 14 risk factors, those tied to the greatest proportion of dementia in the global population are hearing impairment and high LDL cholesterol (7% each), along with less education in early life, and social isolation in later life (5% each), the report estimates. The new report also outlines 13 recommendations aimed at individuals and governments to help guard against dementia. They include preventing and treating hearing loss, vision loss, and depression; being cognitively active throughout life; using head protection in contact sports; reducing vascular risk factors (high cholesterol, diabetes, obesity, hypertension); improving air quality; and providing supportive community environments to increase social contact. Dr. Tara Spires-Jones, PhD, president of the British Neuroscience Association, emphasized that while this research doesn't directly link specific factors to dementia, it supports evidence that a healthy lifestyle — encompassing education, social activities, exercise, cognitive engagement, and avoiding head injuries and harmful factors for heart and lung health — can enhance brain resilience and prevent dementia. In an interview with Medscape Medical News, Heather M. Snyder, PhD, senior vice president of medical and scientific relations, Alzheimer's Association, said, "Our brains are complex and what happens throughout our lives may increase or decrease our risk for dementia as we age. Protecting brain health as we age requires a comprehensive approach that includes discussions on diet, exercise, heart health, hearing, and vision." Also weighing in on the new report, Shaheen Lakhan, MD, PhD, neurologist and researcher based in Miami, Florida, said the addition of high cholesterol is "particularly noteworthy as it reinforces the intricate connection between vascular health and brain health — a link we've long suspected but can now target more effectively." As for vision loss, "it's not just a matter of seeing clearly; it's a matter of thinking clearly. Untreated vision loss can lead to social isolation, reduced physical activity, and cognitive decline," said Lakhan. Dementia Is Not Inevitable In his view, "the potential to prevent or delay nearly half of dementia cases by addressing these risk factors is nothing short of revolutionary. It shifts our perspective from viewing dementia as an inevitable part of aging to seeing it as a condition we can actively work to prevent," Lakhan added. He said the report's emphasis on health equity is also important. "Dementia risk factors disproportionately affect socioeconomically disadvantaged groups and low- and middle-income countries. Addressing these disparities isn't just a matter of fairness in the fight against dementia, equality in prevention is as important as equality in treatment," Lakhan commented. While the report offers hope, it also presents a challenge, he said. Implementing the recommended preventive measures requires a "coordinated effort from individuals, healthcare systems, and policymakers. The potential benefits, both in terms of quality of life and economic savings, make this effort not just worthwhile but imperative. Preventing dementia is not just a medical imperative — it's an economic and humanitarian one," Lakhan said. Masud Husain, PhD, with University of Oxford, UK, agreed. The conclusions in this report are "very important for all of us, but particularly for health policy makers and government," he told the Science Media Centre. "If we did simple things well such as screening for some of the factors identified in this report, with adequate resources to perform this, we have the potential to prevent dementia on a national scale. This would be far more cost effective than developing high-tech treatments, which so far have been disappointing in their impacts on people with established dementia," Husain said. Note: This article originally appeared on Medscape .

A multicomponent nonpharmaceutical intervention improves sleep in people with dementia living at home, early results of a new phase 3 randomized controlled trial (RCT) show. The benefits of the intervention — called DREAMS-START — were sustained at 8 months and extended to caregivers, the study found. "We're pleased with our results. We think that we were able to deliver it successfully and to a high rate of fidelity," said study investigator Penny Rapaport, PhD, Division of Psychiatry, University College London, United Kingdom. The findings were presented on July 30 at the Alzheimer's Association International Conference (AAIC) 2024 . Sustained, Long-Term Effect Sleep disturbances are very common in dementia. About 26% of people with all types of dementia will experience sleep disturbances, and that rate is higher in certain dementia subtypes, such as dementia with Lewy bodies, said Rapaport. Such disturbances are distressing for people living with dementia as well as for those supporting them, she added. They're "often the thing that will lead to people transitioning and moving into a care home." Rapaport noted there has not been full RCT evidence that any nonpharmacologic interventions or light-based treatments are effective in improving sleep disturbances. Medications such as antipsychotics and benzodiazepines aren't recommended as first-line treatment in people with dementia "because often these can be harmful," she said. The study recruited 377 dyads of people living with dementia (mean age, 79.4 years) and their caregivers from 12 national health service sites across England. "We were able to recruit an ethnically diverse sample from a broad socioeconomic background," said Rapaport. Researchers allocated the dyads to the intervention or to a treatment as usual group. About 92% of participants were included in the intention-to-treat analysis at 8 months, which was the primary time point. The intervention consists of six 1-hour interactive sessions that are "personalized and tailored to individual goals and needs," said Rapaport. It was delivered by supervised, trained graduates, not clinicians. The sessions focused on components of sleep hygiene (healthy habits, behaviors, and environments); activity and exercise; a tailored sleep routine; strategies to manage distress; natural and artificial light; and relaxation. A whole session was devoted to supporting sleep of caregivers. The trial included masked outcome assessments, "so the people collecting the data were blinded to the intervention group," said Rapaport. The primary outcome was the Sleep Disorders Inventory (SDI) score. The SDI is a questionnaire about frequency and severity of sleep-disturbed behaviors completed by caregivers; a higher score indicates a worse outcome. The study adjusted for baseline SDI score and study site. The adjusted mean difference between groups on the SDI was -4.7 points (95% CI, -7.65 to -1.74; P = .002) at 8 months. The minimal clinically important difference on the SDI is a 4-point change, noted Rapaport. The adjusted mean difference on the SDI at 4 months (a secondary outcome) was - 4.4 points (95% CI, -7.3 to -1.5; P = .003). Referring to illustrative graphs, Rapaport said that SDI scores decreased at both 4 and 8 months. "You can see statistically, there's a significant difference between groups at both time points," she said. "We saw a sustained effect, so not just immediately after the intervention, but afterwards at 8 months." As for other secondary outcomes, the study found a significant reduction in neuropsychiatric symptoms among people with dementia at 8 months in the intervention arm relative to the control arm. In addition, sleep and anxiety significantly improved among caregivers after 8 months. This shows "a picture of things getting better for the person with dementia, and the person who's caring for them," said Rapaport. She noted the good adherence rate, with almost 83% of people in the intervention arm completing four or more sessions. Fidelity to the intervention (ie, the extent to which it is implemented as intended) was also high, "so we feel it was delivered well," said Rapaport. Researchers also carried out a health economics analysis and looked at strategies for implementation of the program, but Rapaport did not discuss those results. Encouraging Findings Commenting for Medscape Medical News, Alex Bahar-Fuchs, PhD, Faculty of Health, School of Psychology, Deakin University, Victoria, Australia, who co-chaired the session featuring the research,said the findings of this "well-powered" RCT are "encouraging," both for the primary outcome of sleep quality and for some of the secondary outcomes for the care-partner. "The study adds to the growing evidence behind several nonpharmacological treatment approaches for cognitive and neuropsychiatric symptoms of people with dementia," he said. The results "offer some hope for the treatment of a common disturbance in people with dementia which is associated with poorer outcomes and increased caregiver burden," he added. An important area for further work would be to incorporate more objective measures of sleep quality, said Bahar-Fuchs. Because the primary outcome was measured using a self-report questionnaire (the SDI) completed by care-partners, and because the intervention arm could not be blinded, "it remains possible that some detection bias may have affected the study findings," said Bahar-Fuchs. He said he would like to see the research extended to include an active control condition "to be able to better ascertain treatment mechanisms." Note: This article originally appeared on Medscape .

TOPLINE: Mental health disorders increase the likelihood of developing chronic diabetic complications and vice versa across all age groups in patients with type 1 diabetes (T1D) or type 2 diabetes (T2D). METHODOLOGY: Understanding the relative timing and association between chronic diabetic complications and mental health disorders may aid in improving diabetes screening and care. Researchers used a US national healthcare claims database (data obtained from 2001 to 2018) to analyze individuals with and without T1D and T2D, who had no prior mental health disorder or chronic diabetic complication. The onset and presence of chronic diabetic complications and mental health disorders were identified to determine their possible association. Individuals were stratified by age: 0-19, 20-39, 40-59, and ≥ 60 years. TAKEAWAY: Researchers analyzed 44,735 patients with T1D (47.5% women) and 152,187 with T2D (46.0% women), who were matched with 356,630 individuals without diabetes (51.8% women). The presence of chronic diabetic complications increased the risk for a mental health disorder across all age groups, with the highest risk seen in patients aged ≥ 60 years (hazard ratio [HR], 2.9). Similarly, diagnosis of a mental health disorder increased the risk for chronic diabetic complications across all age groups, with the highest risk seen in patients aged 0-19 years (HR, 2.5). Patients with T2D had a significantly higher risk for a mental health disorder and a lower risk for chronic diabetic complications than those with T1D across all age groups, except those aged ≥ 60 years. The bidirectional association between mental health disorders and chronic diabetic complications was not affected by the diabetes type (P > .05 for all interactions). IN PRACTICE: "Clinicians and healthcare systems likely need to increase their focus on MHDs [mental health disorders], and innovative models of care are required to optimize care for both individuals with type 1 diabetes and those with type 2 diabetes," the authors wrote. LIMITATIONS: The study relied on International Classification of Diseases 9th and 10th revision codes, which might have led to misclassification of mental health conditions, chronic diabetes complications, and diabetes type. The data did not capture the symptom onset and severity. The findings may not be generalizable to populations outside the United States. DISCLOSURES: The study was supported by the Juvenile Diabetes Research Foundation (now Breakthrough T1D). Some authors reported receiving speaker or expert testimony honoraria and research support, and some declared serving on medical or digital advisory boards or as consultants for various pharmaceutical and medical device companies. Note: This article originally appeared on Medscape .

Lauren Opladen remembers the agonizing wait all too well. At age 17, struggling with paralyzing depression after losing her brother to suicide and her father to amyotrophic lateral sclerosis, her teacher suggested she seek help. So, she did. But she had to spend 3 days inside an emergency department at the University of Rochester Medical Center in Rochester, New York, where the Comprehensive Psychiatric Emergency Program (CPEP) provides immediate care for youth and adults experiencing psychiatric emergencies. “We were sleeping on a couch just waiting for all these services, when that’s precious time wasted,” Ms. Opladen said. Ms. Opladen made it through that dark period, and 5 years later, she is a registered nurse at the same hospital. Every day she walks past a new facility she wishes had existed during her troubled teenage years: An urgent care center for children and adolescents experiencing mental health crises. Brighter Days Pediatric Mental Health Urgent Care Center, Rochester, New York, opened in July as a walk-in clinic offering rapid assessment, crisis intervention, and short-term stabilization, provides referrals to counseling or psychiatric care. Children and adolescents at immediate risk of harming themselves or others, or who need inpatient care, are sent to CPEP or another emergency department in the area. Similar walk-in facilities linking youth to longer-term services are popping up in nearly a dozen states, including New York, Ohio, Massachusetts, and Wisconsin. The emerging model of care may offer a crucial bridge between traditional outpatient services and emergency room (ER) visits for some young people experiencing mental health crises. “We’ve seen a significant increase in the number of children and adolescents presenting to emergency departments with mental health concerns,” said Michael A. Scharf, MD, chief of the Division of Child and Adolescent Psychiatry at the University of Rochester Medical Center, who oversees operations at Brighter Days. “These urgent care centers provide a more appropriate setting for many of these cases, offering specialized care without the often overwhelming environment of an ER.” The urgency of addressing youth behavioral health has become increasingly apparent. The most recent data from the US Centers for Disease Control and Prevention showed that over a 6-month period in 2020, during the early months of the COVID-19 pandemic, visits to the emergency department for mental health problems spiked 24% among children aged 5-11 years and 31% among 12-17-year-olds compared with the same period in 2019. Between March 2021 and February 2022, such emergency visits rose by 22% for teen girls, while falling by 15% for boys ages 5-12 years and 9% for older boys. Most visits occur during the school year. But staffing shortages and limited physical space are taxing the capacity of the healthcare system to screen, diagnose, and manage these patients, according to a 2023 report published in Pediatrics. Urgent Care: A Misnomer? Some in the mental health community said the label “urgent” in these centers’ titles is misleading. Brighter Days and similar facilities do not conduct involuntary holds, administer medication, or handle serious cases like psychotic episodes. David Mathison, MD, senior vice president of clinic operations at PM Pediatrics, a chain of pediatric urgent care clinics in Maryland, said patients and their families may mistakenly believe the centers will address mental health problems quickly. “It’s really not urgent behavioral health. It’s really just another access point to get behavioral health,” Dr. Mathison said. “Crises in pediatrics are so much more complex” than physical injuries or acute infections, which are the bread and butter of urgent care centers. “An urgent care center almost implies you’re going to come in for a solution to a simple problem, and it’s going to be done relatively quickly on demand, and it’s just not what the behavioral health centers do,” he said. Dr. Mathison, who also serves on the executive committee for the section on urgent care at the American Academy of Pediatrics, likened the centers to in-person versions of crisis center hotlines, which offer virtual counseling and talk therapy and may refer individuals to specialists who can provide clinical care over the long term. Instead, Brighter Days and other centers provide crisis de-escalation for individuals experiencing an exacerbation of a diagnosed mental illness, such a manic episode from bipolar disorder. “Most places aren’t just going to change their therapy without either contacting their psychiatrist or having psychiatrists on staff,” Dr. Mathison said. Other challenges at Brighter Days and similar centers include staffing with appropriately trained mental health professionals, given the nationwide shortage of child and adolescent psychiatrists, Dr. Scharf said. The number of child and adolescent psychiatrists per 100,000 children varies significantly across states. Nationally, the average stands at 14 psychiatrists per 100,000 children, but ranges from as low as 4 to 65, according to the American Academy of Child & Adolescent Psychiatry . For now, Dr. Scharf said, patients who visit Brighter Days are billed as if they are having a routine pediatric office visit as opposed to a pricier trip to the emergency department. And the center accepts all individuals, regardless of their insurance status. Ms. Opladen said the urgent care center represents a significant improvement over her experience at the emergency department’s psychiatric triage. “I saw how awful it was and just the environment,” she said. “The first thing I thought was, what do I need to do to get out of here?” She said the pediatric mental health urgent care centers are “the complete opposite.” Like Brighter Days, these centers are designed to look more like a pediatrician’s office, with bright welcoming colors and games and toys. “It’s separated from everything else. There’s a welcome, relaxed space,” she said. “The welcoming feel is just a whole different environment, and that’s really how it should be.” A version of this article first appeared on Medscape.com .

Eight commonly used antidepressants have been ranked by their weight gain potential. Results of a large observational study showed small differences in short- and long-term weight change in patients prescribed one of eight antidepressants, with bupropion associated with the lowest weight gain and escitalopram, paroxetine, and duloxetine associated with the greatest. Escitalopram, paroxetine, and duloxetine users were 10%-15% more likely to gain at least 5% of their baseline weight compared with those taking sertraline, which was used as a comparator. Investigators noted that the more clinicians and patients know about how a particular antidepressant may affect patients’ weight, the better informed they can be about which antidepressants to prescribe. “Patients and their clinicians often have several options when starting an antidepressant for the first time. This study provides important real-world evidence regarding the amount of weight gain that should be expected after starting some of the most common antidepressants,” lead author Joshua Petimar, ScD, assistant professor of population medicine in the Harvard Pilgrim Health Care Institute at Harvard Medical School, Boston, said in a press release. The findings were published online in Annals of Internal Medicine . Real-World Data Though weight gain is a commonly reported side effect of antidepressant use and may lead to medication nonadherence and worse outcomes, there is a lack of real-world data about weight change across specific medications. Investigators used electronic health records from eight health care systems across the United States spanning from 2010 to 2019. The analysis included information on 183,118 adults aged 20-80 years who were new users of one of eight common first-line antidepressants. Investigators measured their weight at baseline and at 6, 12, and 24 months after initiation to estimate intention-to-treat (ITT) effects of weight change. At baseline, participants were randomly assigned to begin sertraline, citalopram, escitalopram, fluoxetine, paroxetine, bupropion, duloxetine, or venlafaxine. The most common antidepressants prescribed were sertraline, citalopram, and bupropion. Approximately 36% of participants had a diagnosis of depression, and 39% were diagnosed with anxiety. Among selective serotonin reuptake inhibitors (SSRIs), escitalopram and paroxetine were associated with the greatest 6-month weight gain, whereas bupropion was associated with the least weight gain across all analyses. Using sertraline as a comparator, 6-month weight change was lower for bupropion (difference, 0.22 kg) and higher for escitalopram (difference, 0.41 kg), duloxetine (difference, 0.34 kg), paroxetine (difference, 0.37 kg), and venlafaxine (difference, 0.17 kg). Escitalopram, paroxetine, and duloxetine users were 10%-15% more likely to gain at least 5% of their baseline weight compared with sertraline users. Investigators noted little difference in adherence levels between medications during the study except at 6 months, when it was higher for those who took bupropion (41%) than for those taking other antidepressants (28%-36%). The study included data only on prescriptions and investigators could not verify whether the medications were dispensed or taken as prescribed. Other limitations included missing weight information because most patients did not encounter the health system at exactly 6, 12, and 24 months; only 15%-30% had weight measurements in those months. Finally, the low adherence rates made it difficult to attribute relative weight change at the 12- and 24-month time points to the specific medications of interest. “Clinicians and patients could consider these differences when making decisions about specific antidepressants, especially given the complex relationships of obesity and depression with health, quality of life, and stigma,” the authors wrote. The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases. Disclosures are noted in the original article. Note: This article originally appeared on MDedge .

PHILADELPHIA — An experimental, cell-based therapy met its primary safety and secondary efficacy endpoints in a phase 2a study on mild Alzheimer's disease (AD). The results "exceeded our expectations" in terms of "consistent positive efficacy signals" across different domains, including cognition, quality of life, and neuroimaging results, Joshua Hare, MD, co-founder, chief science officer, and chairman of Longeveron, which developed the treatment, told Medscape Medical News. The findings were presented on July 28 at the Alzheimer's Association International Conference (AAIC) 2024 . FDA Fast Track Designation Earlier this month, the US Food and Drug Administration (FDA) granted Lomecel-B Regenerative Medicine Advanced Therapy designation and Fast Track designation for the treatment of mild AD. Lomecel-B is a living cell product made from medicinal signaling cells isolated from the bone marrow of young, healthy, adult donors. These specialized cells have been shown to perform a number of complex functions in the body, including the formation of new tissue. They also have been shown to respond to sites of injury or disease and secrete bioactive factors that are immunomodulatory and regenerative. Lomecel-B may have multiple potential mechanisms of action that could lead to anti-inflammatory and provascular regenerative responses "and therefore may have broad application for a range of rare and aging related diseases," a company press release noted. In a phase 1 study, a single dose of Lomecel-B had a positive benefit/risk profile and suggested clinical benefits in cognitive function and in offsetting hippocampal atrophy. The phase 2a CLEAR MIND study tested single and multiple dosing regimens of Lomecel-B vs placebo in 48 patients, aged 60-85 years, with a diagnosis of mild AD by National Institutes of Health-Alzheimer's Association criteria, a Mini-Mental State Examination (MMSE) score of 18-24, and a brain MRI and PET scan consistent with AD. On the primary outcome of safety, the study confirmed the established safety profile of Lomecel-B for single and multiple dosing regimens, with no hypersensitivity or infusion-related reactions and no cases of amyloid-related imaging abnormalities. On the secondary efficacy measures, treatment with Lomecel-B was associated with an overall slowing of disease worsening compared with treatment with placebo. "Positive efficacy results were demonstrated via a change from baseline at week 39 of the trial at prespecified levels using the Composite Alzheimer's Disease Score (CADS) — a secondary outcome measure that combines information across cognitive, functional capacity, and brain MRI domains," the company reported in a press release. Lomecel-B was also associated with slowing cognitive and functional decline as shown by statistically significant results in the Montreal Cognitive Assessment and "statistical trending" improvements compared with placebo in Clinical Dementia Rating-Sum of Boxes and MMSE. A statistically significant improvement relative to placebo was observed in the AD Cooperative Study-Activities of Daily Living, and there was a numerical improvement relative to placebo in quality of life observed by caregivers and measured by AD-Related Quality of Life and Quality of Life-AD scales. Lomecel-B also appeared to slow the progression of brain atrophy in areas associated with AD, which was statistically significant for left hippocampal volume, relative to placebo, and this correlated with clinical outcomes. "The detailed measurement of brain atrophy shows that there's a marked attenuation of the degree of atrophy that develops after treatment," said Hare. Targeting Neuroinflammation In addition, findings on diffusion tensor imaging MRI suggest that Lomecel-B has the potential to reduce neuroinflammation compared with placebo. "This cellular-based therapy is highly effective at targeting neuroinflammation devoid of the side effects of most other anti-inflammatory therapies. Of course, we need to do more studies, but the results of diffusion tensor imaging were incredibly consistent that there was a powerful effect to reduce neuroinflammation," Hare said. The company plans to meet with the FDA shortly to iron out details of the next study. "We have a slight signal that multiple dosing is better than single dosing. One of the primary objectives of the next study that we're planning will be to further nail down dosing regimens," Hare said. Commenting on this research for Medscape Medical News , Heather M. Snyder, PhD, senior vice president of medical and scientific relations, Alzheimer's Association, said, "This is an interesting small study of a promising new approach to Alzheimer's treatment." "The Alzheimer's Association funded some of the prior work leading to this study through the Part the Cloud research funding initiative. The data reported at AAIC 2024 are encouraging but preliminary and need to be replicated in larger studies including representative study populations," Snyder said. "All evidence-based paths to treatment of Alzheimer's and all other dementias should be explored. We are in an era of unprecedented promise, with new treatments in various stages of development that slow, or may possibly prevent, cognitive decline due to Alzheimer's or other disease," she said. "The Alzheimer's Association envisions a future where there are many treatments available that address these diseases in multiple ways and can be combined into powerful combination therapies, most likely in conjunction with brain-healthy lifestyle guidance," she added. Note: This article originally appeared on Medscape .

Keypoint: Why a blue dye may be a viable treatment for psychiatric disorders. Methylene blue is both a dye and a medicine. Methylene blue has been demonstrated to improve depression, as well as anxiety and Alzheimer's disease. Methylene blue also enhances memory. Methylene blue is both a dye and an FDA-approved medication. Described as the first fully synthetic drug used in medicine, methylene blue was initially synthesized by a German chemist in 1876, and 15 years later, it was employed as a treatment for malaria. This dye/medicine continued to play an important role as an antimalarial medication during the First and Second World Wars. In the late 19th century, methylene blue was explored as a treatment for schizophrenia, and later, it was employed as a treatment for urinary tract infections, an antidote for carbon monoxide and cyanide poisoning, and a drug for septic shock. Today, this amazing medicant is being explored as a treatment for neuropsychiatric conditions. The chemical structure of methylene blue is similar to that of both tricyclic antidepressants and the anti-seizure medicine carbamazepine. However it’s mechanisms of action are quite different from these medications. Some of these mechanisms are dose dependent, meaning that higher doses can have the opposite effects of lower doses. The specific mechanisms of methylene blue include antibacterial, antiviral, and anti-inflammatory effects; blockade of GABA-A receptors; inhibition of monoamine oxidase A (MAO-A); improvement in mitochondrial functioning; and inhibition of tau protein aggregation. Methylene blue also affects the transmission of the primary excitatory neurotransmitter in the human brain, glutamate, by inhibiting N-methyl-D-aspartate (NMDA) receptors. This results in an increase in brain-derived neurotrophic factor (BDNF). In this way, methylene blue functions similarly to ketamine and other psychoplastogens such as psilocybin and LSD, but it does not cause alterations in consciousness, such as those produced by psychedelic medicines. Antidepressant effects Since the 1970’s, methylene blue has been found to be an effective antidepressant medicine in multiple studies. For example, a 1986 study performed by researchers in Scotland explored the effects of 15 mg of methylene blue administered daily to 13 women who suffered from severe depression. Their response was compared to 15 women who were given a placebo. The women who received a placebo did not improve, but those who were given methylene blue showed marked improvement. In fact, within one week, the women who were receiving methylene blue showed a statistically significant improvement in their depressive symptoms relative to those in the placebo group. In another study, 24 chronically and/or severely depressed participants were treated with methylene blue 200 mg or 300 mg daily. Nineteen of these individuals were diagnosed with bipolar disorder, and 14 of these showed “definite improvement.” In 1986, a two-year randomized, cross-over study examined the effects of 300 mg versus 15 mg of methylene blue daily in 17 individuals with bipolar disorder . All participants also took lithium throughout the study. The investigators found that individuals who took the higher dose were significantly less depressed than those who took the lower dose, and no change in manic symptoms occurred in either group. Hospitalization rates were reduced following treatment with either dose. Another study involved a double-blind crossover design with men or women who were diagnosed with bipolar I or bipolar II disorder and were partially stabilized on lamotrigine. Participants were randomly assigned to receive either methylene blue at a dose of 15 mg or 195 mg daily for three months, then they were switched to the other dose. They continued to take lamotrigine throughout the study. Twenty-seven individuals completed the study. Methylene blue was well tolerated, and no severe side effects were reported. None of the individuals experienced a worsening of manic symptoms. However, there was an overall reduction in symptoms of depression and anxiety . Methylene blue as a treatment for other psychiatric disorders In 1938, a study described the use of methylene blue as a treatment for schizophrenia. More than 50 years later, another study explored the use of methylene blue in eight patients with schizophrenia who failed to respond to conventional antipsychotic medications. These individuals demonstrated statistically significant improvement following treatment with methylene blue, and their symptoms worsened when the medicine was discontinued. A double-blind, randomized, placebo-controlled Phase II trial involving 321 individuals with mild or moderately severe Alzheimer’s disease found moderate improvement following the administration of 138 mg of methylene blue daily after 24 weeks, but higher (228 mg) and lower (69 mg) doses were ineffective. Methylene blue has also been found to enhance memory and exert neuroprotective effects. Side effects with this medicine, which are typically mild and well tolerated, may include blue-colored urine, nausea, and headache. Summary While newer antidepressant medications often cost hundreds of dollars per month, older therapeutics that can no longer be patented may provide effective and more affordable options for people suffering from psychiatric illnesses who cannot afford more expensive treatments. Methylene blue is one such medicine. Further studies will help us understand more about the potential benefits of this unique therapeutic, as well as its benefits for the treatment of psychiatric and neurodegenerative disorders. Note: This article originally appeared on Psychology Today .

Keypoint: Recent updates in suicide prevention interventions for older adults and how a novel tablet application may provide relief to individuals at high risk of suicide. Suicide in late life constitutes a major public health concern. In 2019, the Centers for Disease Control and Prevention (CDC) reported that the suicide rate for all ages in the United States was 14.5/100,000. Middle-aged and older adults have higher rates of suicide than their younger counterparts (19.41/100,000 for individuals aged 55 to 64), and the highest rate of suicide remains for older males (39.9/100,000 for males aged 75 and older).1 Despite the alarmingly high rates, psychosocial interventions for this population are understudied and urgently needed. Mobile devices provide a unique and powerful opportunity to deliver interventions to suicidal individuals during periods of increased suicide risk.2 With the current COVID-19 pandemic , reliance on digital health technology is growing, and developing targeted interventions that can be used remotely by older adults during times of emotional crisis is of paramount importance. Characteristics and Risk Factors To establish effective psychosocial interventions, risk factors for late-life suicide must be examined. Sociodemographic and clinical factors that are more commonly found in middle-aged and older individuals (eg, widowhood, cognitive decline, etc) play an important role in suicide risk . Understanding the complex interaction of these late-life occurrences can guide efforts in designing preventative interventions. Demographic Factors According to the CDC, middle-aged and older adults account for the highest number of suicides compared to younger populations. In 2018, adults aged 65 and older were reported to make up 16% of the US population, but were responsible for 18.8% of suicides. While there are an estimated 25 suicide attempts for every completed suicide in the general population, approximately 1 in 4 suicide attempts results in death for older adults. Gender, race, and ethnicity also influence suicide risk and behavior. Women consistently account for a higher number of suicide attempts than men. There are 3 female attempts for each male attempt, yet an estimated 3.6 males die by suicide for every 1 female death. This discrepancy is attributed to the difference in method, because men often use more lethal methods when attempting suicide. In comparison to other racial and ethnic groups, non-Hispanic American Indian/Alaska Native and non-Hispanic white people account for the highest rates of suicide at 22.3 and 17.6/100,000, respectively. Cognitive Functioning and Physical Illness As many as 1 in 9 older adults suffer from some form of cognitive impairment. Cognitive impairment is often responsible for reducing decision-making capacity and affecting emotion regulation abilities, potentially contributing to suicidal ideation and behavior. Discrepancies in literature regarding suicide risk and cognitive impairment suggest that dementia can either be a risk factor or a protective factor depending on the progression and severity of symptoms. However, a review on suicide risk and Alzheimer disease found that Alzheimer disease is associated with a moderate suicide risk in older adults, even several years after diagnosis. Physical illness and functional disability in late life are also strongly associated with suicide. In a cohort study by Erlangsen and colleagues,12 investigators found that certain cancers and liver disease, specifically, are most closely associated with suicidal outcomes. Despite strong associations found in research, reviewers of the literature advise caution when using physical illness to determine risk, many noting that identifying physical illness does not serve as a predictor for suicide, nor does quantifying the severity of symptoms. Psychiatric Illness and Suicidal Behavior Psychiatric illness is noted in up to 97% of late-life suicides, with major depression cited as the most strongly associated psychiatric disorder. Retrospective analysis of psychiatric illness and suicide mortalities in older adults in Denmark highlight recurrent depression as contributing to the highest rate of suicides in adults aged 60 and older, followed closely by other affective disorders and reaction to stress/adjustment disorders. This risk was significantly increased for individuals who were hospitalized for any type of psychiatric disorder, with hospitalized psychiatric illness accounting for 22.3% of male suicides aged 60 and older. One of the predictors of suicidal behavior is suicidal ideation, especially active suicidal ideation with intent or plan. However, in older adults who are seeking aging services, even passive suicidal ideation is an indicator of suicide risk. Despite the elevated number of late-life suicides, suicidal older adults often go undetected due to lower rates of reporting, especially in primary care where older adults most likely seek medical treatment. This information highlights the need for increased identification strategies, as well as enhanced efforts to prevent the onset of suicidal ideation given the high mortality rate in late-life suicide attempters. Psychosocial Factors Interpersonal losses including widowhood or death of friends and family are commonplace in advancement of age. The accompanying stress, sense of loneliness, and social disconnection in response to loss is associated with elevated suicide risk, especially within the first year after the death of a close relative. Passive and active suicidal thoughts are particularly common among older adults in long-term care facilities, and social isolation and loneliness are some of the most frequently reported bases for suicidal thoughts. The relationship between perceived social support and psychiatric illness, most notably depression, is strong even when controlling for other factors, such as negative affectivity and overreporting of experiences. This points toward a need for more dynamic psychosocial interventions. Existing Psychosocial Interventions for Suicide Prevention Current randomized, controlled trials (RCTs) that evaluate psychosocial interventions for older adults are typically developed to address depression or other affective disorders in young adults and are not specifically targeted toward suicidality. Of the few published RCTs that measure suicidal ideation as a primary outcome in older adults, the intervention and assessment methods are diverse. Conwell investigated the effect of a peer companionship program on socially disconnected older adults, but saw no significant difference in suicidal ideation outcomes between the treatment and control groups. Two studies, conducted by Ecker and Kumpula, evaluated adaptations of CBT on veterans with suicidal ideation. The first study was a 4-month brief cognitive behavioral therapy (CBT), and the second was CBT for depression compared against 2 other evidence-based psychotherapies. Both authors reported a reduction in suicidal ideation in the CBT/bCBT groups compared to control groups. Gustavson and Lutz examined suicidal ideation as a primary outcome in tests of problem-solving therapy in older adult populations. These studies both saw significant reductions in suicidal ideation in the treatment groups; however, 1 study tailored the intervention toward older adults with depression and executive dysfunction, and the other targeted subjects with functional disability, making the interventions difficult to compare. Kiosses investigated the effects of problem adaptation therapy (PATH) on suicidal ideation, an intervention that utilizes emotion-regulation techniques and compensatory strategies in older adults with depression and cognitive impairment. The authors saw a reduction in suicidality in the PATH participants, but the reduction was not significantly different from the supportive therapy control group. The samples in the aforementioned studies represent specific populations (ie, veterans with medical illness, older adults with functional disabilities), and are not representative of the general older adult population. The heterogeneity of the interventions creates difficulty in both between-study comparisons and generalizability to the general population. Moreover, these studies often exclude those who express active suicidal ideation, leaving out those who are at greater risk of suicide. The results are promising; however, it is important that findings be replicated with larger and more representative samples to more accurately examine the effectiveness and promote generalizability of the interventions. Role of Technology in Treatment The onset of the COVID-19 pandemic and the associated policies have the potential to exacerbate the severity of the previously identified risk factors for suicide in older adults. Social-distancing guidelines, stress, and limited access to health care may contribute to increased feelings of isolation and loneliness, worsening of cognitive and functional abilities, and intensification of symptoms of psychiatric disorders. Technology offers the opportunity to alleviate logistical barriers to receiving clinical interventions for older adults who may have difficulty adhering to treatment. As the reliance on telehealth increases, more thorough investigation into remote psychosocial intervention methods targeted specifically for this population is particularly essential. Literature on the role of technology treatment for suicide prevention in older adults is sparse. Preliminary findings available on feasibility and acceptability of technology-based mobile interventions suggest promising effects of improvement, but further testing is needed. In a review of mobile health technology for suicide prevention, one intervention, Virtual Hope Box (VHB), was tested in middle-aged adults. The study recruited both young and middle-aged veterans with a mean age of 46 years old and tested an augmentation of CBT using smartphone capabilities to enhance and personalize the experience with a “hope box.” The study evaluated the effect of the application on intensity of suicidal ideation and importance of reasons for living, but the results yielded no statistically significant treatment effect on these outcomes between the treatment and control groups. Our research at the Emotion, Cognition, and Psychotherapy Lab at Weill Cornell Medicine aims to reduce suicide risk by employing a simplified, personalized, and easy-to-use mobile intervention. WellPATH is a tablet application that focuses on emotion regulation strategies (specifically, cognitive reappraisal strategies, which focus on seeing a situation from a different perspective) to reduce negative emotions associated with increased suicide risk. It is a personalized, mainly standalone, mobile intervention that incorporates patient-specific techniques that can be accessed when the patient is faced with negative emotions. The patient and WellPATH interventionist identify situations, problems, or concerns that trigger intense negative emotions that may lead to increased suicidal ideation or behavior and develop personalized cognitive reappraisal strategies to reduce the intense negative emotions. Preliminary results indicate that patients are able to utilize the user-friendly interface with ease and are highly satisfied with the support provided by WellPATH. The WellPATH application takes into consideration characteristics unique to older adults and offers immediate access to an intervention that is easy to use. It addresses the need for a mobile suicide prevention intervention for middle-aged and older adults at high suicide risk, which is particularly germane, given the increased reliance on telehealth . Concluding Thoughts The topic of suicide in older adults requires greater consideration. Identification of risk factors is valuable in understanding elder suicidality; however, further attention is encouraged for the development and evaluation of effective interventions tailored to older adults. The few psychosocial interventions mentioned show overall promising results, but unfortunately, there is little available data beyond what has been described. The novel WellPATH tablet application has the opportunity to provide relief to individuals at high risk of suicide by offering an immediate intervention to patients in their actual environment. With the rapid increase in population of middle-aged and older adults, the continued exploration of adaptive preventative interventions is essential for safeguarding the well-being of this increasingly vulnerable population. Note: This article originally appeared on Psychiatric Times .

TOPLINE: Reducing screen time for entire families — parents, children, and adolescents — over a 2-week period can improve the mental health of children and adolescents, notably by mitigating issues related to internalizing behavior and by promoting prosocial behavior. METHODOLOGY: Researchers conducted a secondary analysis of a randomized clinical trial including 89 families (181 children and adolescents) from 10 municipalities in Denmark. Of these, 45 families reduced their screen time for leisure to less than 3 hours per week for 2 weeks (86 children; mean age, 8.6 years; 49% girls) and 44 families maintained their usual screen habits (95 children; mean age, 9.5 years; 60% girls). The children and at least one adult member of the families that reduced their screen time had to hand over their smartphones and tablets for 2 weeks. To ensure compliance, television monitors were installed in their homes. The main outcome was the between-group difference in the change in total behavioral difficulties, measured by the Strengths and Difficulties Questionnaire. TAKEAWAY: The total difficulties score was lower among the participants who reduced their use of screen media vs those who maintained their usual screen habits (mean difference, −1.67 points; 95% CI, −2.68 to −0.67). Internalizing, defined as emotional symptoms and peer problems, showed the greatest improvement in those with reduced screen time, with a mean difference of −1.03 points (95% CI, −1.76 to −0.29). Prosocial behavior also improved significantly, with a mean difference of 0.84 points (95% CI, 0.39-1.30). IN PRACTICE: In an invited commentary, Henning Tiemeier, MD, PhD, of the Department of Social and Behavioral Sciences at the Harvard T.H. Chan School of Public Health, in Boston, wrote, "What is so novel about this intervention is that it does not recommend a lasting reduction of screen time to some arbitrary guideline level, but it examines a radical short-term break. This intervention could possibly be repeated, constituting an intermittent break strategy." LIMITATIONS: The open-label nature of the study may have introduced bias in the assessment of behavioral strengths and difficulties. The short-term follow-up of 2 weeks limits the generalizability of the results to long-term effects. The study sample may represent a subgroup with particularly high motivation to reduce the use of screen media, influencing the generalizability of the findings. DISCLOSURES: The SCREENS study was supported by the European Research Council. One of the authors was supported by the UK Medical Research Council and National Institute for Health and Care Research Biomedical Research Centre in Cambridge, England. Another author declared receiving grants from various sources. Note: This article originally appeared on Medscape .

There has been an "alarming" increase in mental health hospital admissions involving methamphetamine use, new research showed. Investigators found that between 2008 and 2020, such admissions increased by more than 10-fold. "Overall, our results show an alarming increase in mental health disorder–related hospitalizations with concurrent methamphetamine use from 2008 to 2020," the investigators led by Diensn Xing, Department of Medicine, Louisiana State University Health Sciences Center at Shreveport, Louisiana, wrote. "These results are especially concerning because these hospitalizations outpace hospitalizations for methamphetamine use alone or mental health disorders alone," they added. The study was published online on June 26 in Nature Mental Health . Action Needed Mental illness and methamphetamine use are both growing health problems. The investigators pointed out that methamphetamine use can cause serious harm to an individual's mental, emotional, and social well-being and can significantly alter the brain. They added that long-term methamphetamine users can exhibit "extreme anxiety, confusion, troubled sleep, mood changes, and aggressive behavior." In addition, use of the drug can cause psychotic side effects such as paranoia, hallucinations, delusions, and suicidality. The investigators noted that to date, no studies have examined the combined effects of both diseases or characterized national trends over more than 10 years. The researchers analyzed US mental health–related trends in methamphetamine users from 2008 to 2020. In particular, they wanted to characterize which demographic and geographic groups might be affected by both of these diseases because people with mental illness and co-occurring methamphetamine use are an "intersectional group" that is "doubly vulnerable to suicide and overdose death due to the synergistic effects of methamphetamine and mental health disorders." Investigators evaluated US trends in mental health disorder–related hospital admissions (MHD-HAs) and compared them with mental health admissions that involved concurrent methamphetamine use (MHD-HA-MUs) between 2008 and 2020. Using data from the largest US inpatient care database, which encompasses more than 7 million hospital stays annually, they examined close to 4 million weighted hospital admissions and found more than a 10-fold increase in MHD-HA-MUs, compared with a 1.4-fold increase in MHD-HAs. MHD-HA-MUs increased significantly among men (13-fold), non-Hispanic Black patients (39-fold), and those aged 41-64 years (16-fold). In the southern United States, MHD-HA-MUs increased 24-fold, larger than in any other region in the United States. "Overall, the data suggest that there are synergistic effects with methamphetamine use and mental health disorder, highlighting this patient group's unique needs, requiring distinct action," the researchers wrote. They proposed several interventions, including public education about substance use disorders, mental illness, and the effects of stigma. They also suggested decreasing criminal penalties for those with substance use disorders and improving healthcare delivery for this patient population. This work was supported by the National Institutes of Health (NIH) and an award from the National Institute of General Medical Sciences of the NIH. Xing and coauthors declared no relevant financial relationships. Note: This article originally appeared on Medscape .

How common are psychiatric disorders in unhoused individuals? Key points: Psychiatric illnesses are common in unhoused individuals, and the prevalence appears to be increasing. Substance use disorders, including alcohol use disorder, occur in over 40% of the unhoused population. About 14% of unhoused persons have a psychotic disorder. Interventional approaches should address both housing and mental health care. Homelessness can predispose individuals to psychiatric disorders. Conversely, certain psychiatric disorders can increase the risk of becoming homeless. A recent article in JAMA Psychiatry by Rebecca Barry, Dallas Seitz, and colleagues provides important information about the prevalence of specific psychiatric disorders in persons who are experiencing homelessness. These authors performed a meta-analysis of data reported in 85 research articles. They selected these articles because they fulfilled rigorous quality criteria and included diagnoses based on the International Classification of Disease (ICD), the Diagnostic and Statistical Manual of Mental Disorders (DSM), or standardized diagnostic instruments. They excluded studies on suicide, self-harm, cognitive impairment (except dementia), neurological disorders, and smoking. They also excluded studies where the entire population was likely to have a psychiatric diagnosis; for example, studies focusing on patients in psychiatric clinics. Most studies defined “homeless” as living in shelters or in places not intended as a permanent dwelling. The final analysis examined data from 48,414 unhoused adults (18 years and older). Current psychiatric disorders Overall, the investigators found that two-thirds (67%) of unhoused persons were diagnosed with a current psychiatric disorder. The most common was substance use disorder. Alcohol use disorder occurred in over 25% of these individuals, and substance use disorders, including alcohol use disorder, occurred in over 43%. Unhoused individuals experienced psychotic disorders at a markedly increased rate compared to the general population. In some studies, about 14% of those experiencing homelessness were diagnosed with a psychotic disorder. In other studies, about 7% were diagnosed with schizophrenia and 8% with bipolar disorder. Although not specifically reported in this study, many individuals with psychotic disorders also have substance use disorders. Antisocial personality disorder, major depression, anxiety disorders, and post-traumatic stress disorder were also common in unhoused individuals, occurring in about 26%, 19%, 14%, and 10.5%, respectively. The overall lifetime prevalence of psychiatric disorders among individuals experiencing homelessness was estimated to be 75%. It was higher for men (86%) than for women (69%). Important trends The authors report that there are indications that the prevalence of current mental illness in unhoused populations may be increasing. In studies conducted prior to 2010, the prevalence was 48% compared with 76% in studies reported after 2010. Implications The great majority of unhoused individuals have a current psychiatric disorder. Homelessness may exacerbate psychiatric disorders, and certain psychiatric disorders may increase the risk of homelessness. For strategies addressing the mental health needs of unhoused individuals to be most successful, access to both housing and mental health treatment must be considered. In addition, better access to quality mental health care may help prevent some individuals from experiencing homelessness in the first place. Note: This article originally appeared on Psychology Today .

Alzheimer's disease (AD), which affects approximately 6.9 million people in the United States, is a progressive neurodegenerative disorder marked by cognitive and behavioral impairment that significantly affects social and occupational functioning. AD typically occurs in patients over age 65 years, but research has uncovered a subtype of AD, early-onset Alzheimer's disease (EOAD), that affects people younger than age 65 years. Because EOAD (also referred to as younger- or earlier-onset AD) represents only about 200,000 AD cases in the United States, it poses unique diagnostic challenges. Symptoms are frequently misattributed to other medical conditions more common in younger individuals (eg, depression, menopause, stress). It is also often misdiagnosed as frontotemporal dementia. Consequently, patients with EOAD often must endure an arduous and frustrating testing process before receiving an accurate diagnosis. Current research is making strides to better define the clinical characteristics of this AD variant, laying the groundwork for promising improvements in diagnostic accuracy. Understanding Early-Onset Alzheimer's Disease Although both late-onset AD (LOAD) and EOAD are marked by beta-amyloid plaques, neurofibrillary tangles (abnormal accumulations of tau protein), and progressive neuronal damage, there are several substantial key distinctions between the two types. Like LOAD, EOAD includes a wide range of symptoms, with memory loss being one of the most prominent. EOAD, however, often presents with atypical nonamnestic cognitive deficits, including language difficulties, visual and spatial deficits, impaired motor skills, and behavioral changes. Several small-scale studies suggest that EOAD progression may be more aggressive compared with LOAD. One retrospective cohort study, which compared neuropsychological assessments of participants with EOAD or LOAD vs those of healthy controls, found that the EOAD group exhibited more pronounced deficits in visual perception, praxis, and executive tasks. Another cohort study, involving 1538 LOAD patients and 387 EOAD patients assessed at specific intervals post-diagnosis, revealed a higher prevalence of behavioral and psychological symptoms of dementia in the EOAD group. Challenges in Diagnosis In addition to nonamnestic presenting symptoms and a more aggressive disease course, a significant difference exists in the time to diagnosis between EOAD and LOAD. On average, EOAD has a longer delay in diagnosis — approximately 1.6 years. This delay can be attributed to several factors, including atypical presenting symptoms, the absence of cognitive screening tests to detect symptoms, and the frequent misdiagnosis of AD symptoms as psychiatric illness. The extended time to diagnosis often results in substantial losses, including time and financial resources, which can be devastating for patients. Other risks associated with delayed diagnosis include treatment delays, anxiety related to prolonged uncertainty, and increased caregiver burden. Additionally, the psychological impact of an EOAD diagnosis is significant. Patients with EOAD have a higher likelihood of developing depression compared with patients with LOAD, according to a recent case study. Although an AD diagnosis is devastating at any age, individuals diagnosed with EOAD are often in their prime, which may lead to an unexpected sense of loss personally and professionally. Patients with EOAD also appear to experience a more rapid cognitive decline. Multidisciplinary Approach to Diagnosis Primary care physicians (PCPs) are often the first clinicians to identify cognitive deficits that require further assessment and follow-up. Numerous barriers to cognitive screening exist within the primary care setting, however, including lack of specialized training and time constraints. A special report released by the Alzheimer's Association in 2020, based on a national survey of PCPs, highlighted the challenges they face in diagnosing dementia. Survey findings revealed that 53% of PCPs receive questions from patients about AD or other forms of dementia every few days, and 27% are "only sometimes or never comfortable" answering their questions. Consequently, 32% of PCPs refer patients to specialists for diagnosis and follow-up care at least once a month. The importance of a multidisciplinary care team in the diagnostic process cannot be overstated. A prospective study involving 439 patients with suspected AD compared independent diagnostic evaluations by a single clinician vs a multidisciplinary team of dementia experts, including physicians and nurses. The study showed that the multidisciplinary team achieved higher accuracy in etiologic diagnosis compared with the single clinician. Moreover, a series of international working group meetings with diverse dementia experts underscored the necessity of a patient-centered multidisciplinary approach to AD diagnosis. Specifically, the group advocated the development of a subspecialty of "dementia-trained" healthcare professionals who would serve as experts, contributing to accurate and timely diagnoses. Diagnostic Tools and Techniques Current diagnostic recommendations for AD encompass a combination of cognitive, functional, and behavioral assessments, supplemented by imaging and cerebrospinal fluid (CSF) and plasma biomarker assays. While these tools are beneficial, they have notable limitations. Commonly used cognitive assessment tools, such as the Mini-Mental State Examination (MMSE), can accurately identify memory and language deficits but are limited in detecting executive functioning impairments, which are often present in EOAD. Amyloid PET scans can confirm the presence of beta-amyloid plaques in the brain. CSF biomarkers serve as an alternative to amyloid PET scans, but lumbar puncture is invasive and may lead to postprocedure complications. Patients with EOAD are frequently excluded from studies and clinical trials owing to their atypical symptoms and younger age. The Longitudinal EOAD Study (LEADS) is a prospective longitudinal study following 400 participants with EOAD and 100 age-matched controls. The goals of LEADS are to define the clinical and biological characteristics of EOAD, develop specific biomarkers for future research, and establish a trial-ready network. This study is among the first to focus specifically on EOAD, representing a significant step toward achieving more timely and accurate diagnoses for this particular subgroup. Promising Advances in Diagnosis Research has increasingly focused on identifying blood-based biomarkers that can detect AD before clinical symptoms appear. One particularly promising biomarker is phosphorylated tau 217 (p-tau217). In March 2024, the US Food and Drug Administration granted breakthrough device designation for the Simoa phospho-Tau 217 blood test, which is designed for earlier detection of AD. While further research is warranted, especially regarding EOAD diagnosis, the development of an accurate blood biomarker is a significant advance toward more timely and precise AD diagnosis. Additionally, the development of smartphone and mobile applications capable of administering cognitive tests is a promising tool for early AD detection. Although still in early development, a small cohort study involving 360 participants with a family history of frontotemporal lobal degeneration utilized mobile devices for cognitive testing. The findings suggest that smartphone-based assessments could become reliable tools for early dementia diagnosis. Although EOAD poses distinct diagnostic challenges owing to its atypical presentation and age of onset, these advances in diagnostic techniques offer hope for early detection in the future. Furthermore, a multidisciplinary approach to diagnosis, involving healthcare practitioners who specialize in dementia, can enhance diagnostic accuracy and patient care. Note: This article originally appeared on Medscape .