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  • Reply to: The FDA Approves Aducanumab for Alzheimer’s Disease, Raising Important Scientific Questions   1 week 1 day ago

    When Jack asks “Who was able to buy low-cost shares from Biogen stock prior to share prices zooming 38% after June 7, adding $16 billion to the company’s market value?” I say “the insiders” who somehow knew Aduhelm was going to be approved by the FDA. In short, “sell high buy low”, that is how the stock market operates. With the price of $56,000 per patient-year, Aduhelm can easily be a $56 billion drug which does not work, and does not help anybody except Biogen and investors. Unless . . .

  • Reply to: Kristian Steen Frederiksen   1 month 1 week ago

    No comments

  • Reply to: Levels of Retinal Amyloid-β Correlate with Levels of Retinal IAPP and Hippocampal Amyloid-β in Neuropathologically Evaluated Individuals.   2 months 2 weeks ago

    The paper is interesting because, consistent with the recent scientific literature, it contributes to the characterization of the different Aβ isoforms deposited in the retina of AD patients, with the aim of identifying new in vivo approaches and tools that allow an early diagnosis of Alzheimer's disease.

  • Reply to: Neurobiology of COVID-19.   2 months 2 weeks ago

    Comprehensive review concerning a topic still largely unknown at the time of publication in JAD (2020) and concerning the issues of Covid in relation to the CNS-

  • Reply to: What is the Purpose of Medicine When Dealing with Incurable Alzheimer’s Disease?   3 months 3 days ago

    Looking back to the last thirty years in the field of AD we can see how the amyloid cascade hypothesis has permeated most of the researches and dominated the clinical and therapeutic approach. Unfortunately, as it often happens—but it should not—in the world of science, the landscape of research became narrower and narrower and many other hypotheses, and so possibilities to understand and offer new chances to efficacious treatments, have been discarded.

    The attitude to walk all together in the mainstream can be comfortable but not useful to open further views in sciences. And this is what happened in the AD world.

    Now we are still waiting for disease-modifying drugs and the approved drugs (the last one twenty years ago) have limited efficacy.

    What did go wrong? Probably a pervasive “street light effect”, looking at what it is easier to see, caused a too long-lasting shortcut that, as a final result, offers no effective treatments to an increasing number of patients.

    Maybe we should start again, of course accepting amyloid and tau as characteristics of AD, but looking up to the main risk factor of dementia: aging [1]. The aging brain is the battlefield where protein aggregation, inflammatory factors, mitochondrial alterations, energy reduction, oxidative stress are the resulting paths due to conditions that start many years before: diabetes, hypertension, heart diseases, metabolic problems, hypoxia due to pulmonary diseases, pollution, psychological stress and whatever can happen in your life.

    So starting to act more strenuously for prevention is the first action that we must consider and new studies have recently shown how the incidence rate of dementia in Europe and North America has declined by 13% per decade over the past 25 years [2] suggesting that probably a more controlled lifestyle is protective against dementia, one of the several age-related diseases.

    It is conceivable that acting for maintaining a good health status along with life and acting for healthy aging is the main action to defeat dementia. Cells, tissue, organs are built up to self-guarantee their survival for a certain time. In the last century, humans have created the opportunity to live much longer than biologically established. Now we need to learn how to slow the biological decline due to aging [3]. Acting against the many diseases that we face during life, i.e., acting to prevent and not to cure, is the main chance we have to avoid, or almost postpone, dementia in old age. What we still called AD, in old age, when its prevalence steeply increases, is not a one-cause disease but the convergence of many factors that we need to manage with a healthier lifestyle.
    Furthermore, allowing exploring pathogenetic hypotheses other than the amyloid cascade  is fundamental to broaden the horizons of research since, quoting the philosopher Karl Popper  “Whenever a theory appears to you as the only possible one, take this as a sign that you have neither understood the theory nor the problem which it was intended to solve”  

    [1] Mecocci P, Boccardi V (2021) The impact of aging in dementia: It is time to refocus attention on the main risk factor of dementia. Ageing Res Rev 65, 101210.
    [2] Wolters FJ et al., (2020) Twenty-seven-year time trends in dementia incidence in Europe and the United States: The Alzheimer Cohorts Consortium. Neurology 95, e519-e531.
    [3] Mecocci P, Baroni M, Senin U, Boccardi V (2018) Brain aging and late-onset Alzheimer's disease: a matter of increased amyloid or reduced energy? J Alzheimers Dis 64 (s1), S397-S404.

  • Reply to: What is the Purpose of Medicine When Dealing with Incurable Alzheimer’s Disease?   3 months 4 days ago
    There is some fundamental food for thought in this blog. The question of the role of a physician for a not curable disease is a key one, as we are forced to think about Osler's vision of patient-centered, value-based medicine. This is the paradigm shift needed:  moving from the one cause - one mechanism - one therapy approach to the conscious avoidance of the Ockham's razor. While razors in medicine can be very important because of their ability to shave off complex problems using heuristics to enable better decisions, they can be - as every razor - extremely dangerous: in this case, if used in the frame of "one size fits all" in a disease afftecting old and very old persons in over 2/3 of the cases. In other words, evidence, recommendations, and guidelines help to orientate diagnosis in cognitive impairment with and without dementia, but do not disentangle complexity. There are no "too complex" problems in the medicine of the aged, rather problems exists, which base on age-related physiologic changes and need to be uncovered.   
    Geriatric medicine, which was first described (also in highest impact journals) by a british female surgeon, Marjory Warren, uses since its foundation a patient-centered approach based on functions, measured with the cornestone of this discipline - the comprehensive assessment. During the performance of the multidimensional assessment, the doctor disentangles complexity and puts together the puzzle of the real-life patient with dementia: old-old or oldest-old, female, multimorbid, frail - quite different from the typical RCT participant. And it is also (mainly?) due to the obsessive fixation on the one cause - one mechanism - one therapy spotlight that so many trials don't work. I started as a physician and researcher now 30 years ago to work on cognitive impairment. And it is frankly quite a pity that the medical scene did not show any substantial innovative, resilient, sustainable approach to this dramatic condition in such a long time.