Digging Deeper: What Can We Really Learn about Dementia from History?

In response to Finch and Burstein's provocative argument that the advanced dementias may result from environmental toxins and lifestyle factors associated with post-industrial societies, we call for a more rigorous historical approach, emphasizing the importance of situating ancient texts more fully in their historical and cultural context. Such an approach would also entail consideration of the declining relative rates of dementia in Western countries, which have been linked to population health-level factors and policies that appear to have reduced the risk of dementia by directly and indirectly influencing the social determinants of brain health.

Making the Case for the Accelerated Withdrawal of Aducanumab.

U.S. Food and Drug Administration-s (FDA) approval of aducanumab (Aduhelm® in the US) as a treatment for mild cognitive impairment of the Alzheimer type and Alzheimer-s disease has raised such major concerns about efficacy, safety, FDA processes, and regulatory capture that Biogen-s license to market this biologic should be immediately withdrawn. Aducanumab has not demonstrated benefit to patients, failed to meet regulatory guidelines, and is likely to cause both individual and societal harm.

Making the Case for Accelerated Withdrawal of Aducanumab.

The controversial approval in June 2021 by the Food and Drug Administration (FDA) of aducanumab (marketed as Aduhelm), Biogen's monoclonal antibody for patients with Alzheimer's disease, raises significant concerns for the dementia field and drug approval process, considering its lack of adequate evidence for clinical efficacy, safety issues, and cost. On 15 December 2021, an international group of clinicians, basic science experts, psychological and social science researchers, lay people with lived experience of dementia, and advocates for public health met to discuss making a recommendation for whether aducanumab's approval should be withdrawn. Attendees considered arguments both in favor of and in opposition to withdrawal and voted unanimously to recommend that the FDA withdraw its approval for aducanumab and to support the Right Care Alliance's filing of a formal Citizen Petition to this effect.

Separate and Unequal: A Time to Reimagine Dementia.

The rapid emergence of COVID-19 has had far-reaching effects across all sectors of health and social care, but none more so than for residential long-term care homes. Mortality rates of older people with dementia in residential long-term care homes have been exponentially higher than the general public. Morbidity rates are also higher in these homes with the effects of government-imposed COVID-19 public health directives (e.g., strict social distancing), which have led most residential long-term care homes to adopt strict 'no visitor' and lockdown policies out of concern for their residents' physical safety. This tragic toll of the COVID-19 pandemic highlights profound stigma-related inequities. Societal assumptions that people living with dementia have no purpose or meaning and perpetuate a deep pernicious fear of, and disregard for, persons with dementia. This has enabled discriminatory practices such as segregation and confinement to residential long-term care settings that are sorely understaffed and lack a supportive, relational, and enriching environment. With a sense of moral urgency to address this crisis, we forged alliances across the globe to form Reimagining Dementia: A Creative Coalition for Justice. We are committed to shifting the culture of dementia care from centralized control, safety, isolation, and punitive interventions to a culture of inclusion, creativity, justice, and respect. Drawing on the emancipatory power of the imagination with the arts (e.g., theatre, improvisation, music), and grounded in authentic partnerships with persons living with dementia, we aim to advance this culture shift through education, advocacy, and innovation at every level of society.

Ethical issues in early diagnosis and prevention of Alzheimer disease.

This paper considers ethical issues related to early diagnosis and all forms of prevention of Alzheimer disease and related conditions. It offers a critical view of the current state of scientific, clinical, and social responses to the growing number of older people with cognitive challenges, and suggests how priorities going forward should be different from those receiving most attention today. We begin with a review of global policy efforts, consider the fundamental goals of prevention, examine issues surrounding early diagnosis, explore more deeply values associated with efforts to prevent age associated cognitive decline, and conclude by considering often unexplored ethical issues that contextualize the field and should influence our approaches to the future.

A randomized controlled trial of disclosing genetic risk information for Alzheimer disease via telephone.

PurposeTelephone disclosure of genetic test results can improve access to services. To date, studies of its impact have focused on return of Mendelian risk information, principally hereditary cancer syndromes.MethodsIn a multisite trial of Alzheimer disease genetic risk disclosure, asymptomatic adults were randomized to receive test results in person or via telephone. Primary analyses examined patient outcomes 12 months after disclosure.ResultsData from 257 participants showed that telephone disclosure occurred 7.4 days sooner and was 30% shorter, on average, than in-person disclosure (both P < 0.001). Anxiety and depression scores were well below cutoffs for clinical concern across protocols. Comparing telephone and in-person disclosure protocols, 99% confidence intervals of mean differences were within noninferiority margins on scales assessing anxiety, depression, and test-related distress, but inconclusive about positive impact. No differences were observed on measures of recall and subjective impact. Subanalyses supported noninferiority on all outcomes among apolipoprotein E (APOE) ɛ4-negative participants. Subanalyses were inconclusive for APOE ɛ4-positive participants, although mean anxiety and depression scores were still well below cutoffs for clinical concern.ConclusionTelephone disclosure of APOE results and risk for Alzheimer disease is generally safe and helps providers meet demands for services, even when results identify an increased risk for disease.

Mind-Matter Interactions and the Frontal Lobes of the Brain: A Novel Neurobiological Model of Psi Inhibition.

CONTEXT: Despite a large literature on psi, which encompasses a range of experiences including putative telepathy (mind-mind connections), clairvoyance (perceiving distant objects or events), precognition (perceiving future events), and mind-matter interactions, there has been insufficient focus on the brain in relation to this controversial phenomenon. In contrast, our research is based on a novel neurobiological model suggesting that frontal brain systems act as a filter to inhibit psi and that the inhibitory mechanisms may relate to self-awareness. OBJECTIVE: To identify frontal brain regions that may inhibit psi. DESIGN: We used mind-matter interactions to study psi in two participants with frontal lobe damage. The experimental task was to influence numerical output of a Random Event Generator translated into movement of an arrow on a computer screen to the right or left. Brain MRI was analyzed to determine frontal volume loss. RESULTS: The primary area of lesion overlap between the participants was in the left medial middle frontal region, an area related to self-awareness, and involved Brodmann areas 9, 10, and 32. Both participants showed a significant effect in moving the arrow to the right, i.e., contralateral to the side of primary lesion overlap. Effect sizes were much larger compared to normal participants. CONCLUSIONS: The medial frontal lobes may act as a biological filter to inhibit psi through mechanisms related to self-awareness. Neurobiological studies with a focus on the brain may open new avenues of research on psi and may significantly advance the state of this poorly understood field.

Global perspectives on dementia and art: An international discussion about changing public health policy.

In an era of global environmental deterioration and income inequity, public health faces many challenges, including the growing number of individuals, especially older people, with chronic diseases. Dementia is increasingly being seen not just as a biomedical problem to solve but as a public and community challenge to address more broadly. Concepts like prevention, brain health, and quality of life/well-being are receiving more attention. The engagement of community in addressing these challenges is being seen as critical to successful social adaptation. Arts programs are reinvigorating cultural responses to the growing number of older people with cognitive challenges. The humanities offer ways of understanding the power of words and stories in public discourse and a critical lens though which to view political and economic influences. In this paper, we report on a panel held in London on the occasion of the conference at the Royal Society for Public Health in March, 2017, in which the authors presented. Key issues discussed included problem framing, the nature of evidence, the politics of power and influence, and the development of effective interventions. In this paper, we review the rejection of two policies, one on dementia and one on the arts and humanities in public health, by the American Public Health Association; the emergence of policies in the UK; and some of the state of the art practices, particularly in training, again focusing on the UK.

Ecopsychosocial Interventions in Cognitive Decline and Dementia: A New Terminology and a New Paradigm.

Dementia is a major medical and social scourge. Neither pharmacological nor nonpharmacological interventions and treatments have received sufficient funding to be meaningful in combatting this tsunami. Because the term-"nonpharmacological"-refers to what these interventions are not, rather than what they are, nonpharmacological treatments face a special set of challenges to be recognized, accepted, funded, and implemented. In some ways, the current situation is analogous to using the term "nonhate" to mean "love." This article presents a carefully reasoned argument for using the terminology "ecopsychosocial" to describe the full range of approaches and interventions that fall into this category. These include interventions such as educational efforts with care partners, social support programs for individuals with various levels of dementia, efforts to improve community awareness of dementia, an intergenerational school where persons with dementia teach young children, and the design of residential and community settings that improve functioning and can reduce behavioral symptoms of dementia. The proposed terminology relates to the nature of the interventions themselves, rather than their outcomes, and reflects the broadest range of interventions possible under the present rubric-nonpharmacological. The goal of this new label is to be better able to compare interventions and their outcomes and to be able to see the connections between data sets presently not seen as fitting together, thereby encouraging greater focus on developing new ecopsychosocial interventions and approaches that can improve the lives of those with dementia, their care partners, and the broader society.

Disclosing Pleiotropic Effects During Genetic Risk Assessment for Alzheimer Disease: A Randomized Trial.

BACKGROUND: Increasing use of genetic testing raises questions about disclosing secondary findings, including pleiotropic information. OBJECTIVE: To determine the safety and behavioral effect of disclosing modest associations between apolipoprotein E (APOE) genotype and coronary artery disease (CAD) risk during APOE-based genetic risk assessments for Alzheimer disease (AD). DESIGN: Randomized, multicenter equivalence clinical trial. (ClinicalTrials.gov: NCT00462917). SETTING: 4 teaching hospitals. PARTICIPANTS: 257 asymptomatic adults were enrolled, 69% of whom had 1 AD-affected first-degree relative. INTERVENTION: Disclosure of genetic risk information about AD and CAD (AD+CAD) or AD only (AD-only). MEASUREMENTS: Primary outcomes were Beck Anxiety Inventory (BAI) and Center for Epidemiologic Studies Depression Scale (CES-D) scores at 12 months. Secondary outcomes were all measures at 6 weeks and 6 months and test-related distress and health behavior changes at 12 months. RESULTS: At 12 months, mean BAI scores were 3.5 in both the AD-only and AD+CAD groups (difference, 0.0 [95% CI, -1.0 to 1.0]), and mean CES-D scores were 6.4 and 7.1 in the AD-only and AD+CAD groups, respectively (difference, 0.7 [CI, -1.0 to 2.4]). Both confidence bounds fell within the equivalence margin of ±5 points. Among carriers of the APOE ε4 allele, distress was lower in the AD+CAD groups (difference, -4.8 [CI, -8.6 to -1.0]) (P = 0.031 for the interaction between group and APOE genotype). Participants in the AD+CAD groups also reported more health behavior changes, regardless of APOE genotype. LIMITATIONS: Outcomes were self-reported by volunteers without severe anxiety, severe depression, or cognitive problems. Analyses omitted 33 randomly assigned participants. CONCLUSION: Disclosure of pleiotropic information did not increase anxiety or depression and may have decreased distress among persons at increased risk for 2 conditions. Providing risk modification information about CAD improved health behaviors. Findings highlight the potential benefits of disclosure of secondary genetic findings when options exist for decreasing risk. PRIMARY FUNDING SOURCE: National Human Genome Research Institute.

The music of trees: the intergenerative tie between primary care and public health.

Stories help us frame and understand complex ideas and challenges. Metaphors are particularly powerful linguistic devices that guide and extend our thinking by bridging conceptual domains, for example to consider the brain as a digital computer. Trees are widely used as metaphors for broad concepts like evolution, history, society, and even life itself, i.e. 'the tree of life'. Tree-like diagrams of roots and branches are used to demonstrate historical and cultural relationships, for example, between different species or different languages. In this paper, we describe a theatrical character called a tree doctor which is a living metaphor. A human being, namely the author, lectures, acts or dances as a tree and offers lessons to Homo Sapiens about 'holistic' ideas of health. The character teaches us to not only see the value of our relationships to trees, but the importance of seeing forests as well the individual trees. The metaphorical statement that we should not 'miss the forest for the trees' means we should learn to think of health embedded in systems and communities. In medicine, we too often focus on individual molecules, pharmaceuticals, or even patients and miss the bigger picture of public and environmental health. In a time of great ecological system change, the tree doctor points to broad ethical responsibility for each other and future generations of humans and other living creatures. The character embraces arts and particularly music as a powerful way of infusing purpose and improving the qualities of our lives together, especially as we age. The tree doctor knows the value of intergenerational relationships. But it also points to intergenerative innovations across many cultural domains, disciplines and professions. The tree doctor supports primary care and empowers the value of intergenerational relationships, art and music in the recommendations doctors make to patients to improve their health and well-being.

From Neurodegeneration to Brain Health: An Integrated Approach.

The term "brain health" integrates general health and well-being with cognitive fitness, in the context of an environment that includes the spectrum of positive and negative factors affecting the individual. Brain health incorporates the effects of neurodegeneration in an ecological sense and the effects of environment and health practices on brain function. It also provides a framework for understanding and maximizing cognitive function across the lifespan. Despite decades of research into the pathogenesis of neurodegenerative disorders, our understanding of how to treat them is relatively rudimentary. Unidimensional approaches, such as medication monotherapies, have generally produced negative results in treatment trials. New integrative paradigms that cut across the molecular and cellular level to the individual and societal level may provide new approaches to understand and treat these disorders. This report on proceedings of a multi-disciplinary conference held in Cleveland, Ohio, in October 2013 summarizes research progress in understanding neurodegenerative disorders in a brain health context. A new "brain health" paradigm is essential to finally understand neurodegenerative disorders such as Alzheimer's disease and overcome the relative stand-still in therapeutics research that has characterized the last decade. The authors summarize progress in these emerging areas with the aim of producing new integrated scientific models for understanding brain health, potentially modifying disease course and advancing care for individuals and families affected by neurodegenerative conditions.