Morbus Alzheimer

Morbus Alzheimer^[1] vel Alzheimeranus^[2] est neurodegenerativus hominis morbus chronicus et communissimum dementiae genus, quod degenerat dum progreditur. Adhuc hodie, sanari non potest, atque ad extremum in mortem ducit. Causa adhuc nescitur, quod usitate senescendi non est, etiamsi medicamenta sumi possunt ad symptomata mollienda. Appellatur ex Aloysio Alzheimer, psychiatro, neurologo et neuropathologo Germanico, qui anno 1906 morbum investigavit.

Cave: notitiae huius paginae nec praescriptiones nec consilia medica sunt.

Hodie quidem notioni morbi Alzheimeriani significationes diversae adiunguntur,^[3] verbi gratia definitiones clinicae ac neuropathologicae. Sub microscopio visum cerebrum morbo Alzheimeriano affectum combinationem structurarum pathologicarum duarum conspicuam videri potest: accumulationem enim et macularum extracellularium Amyloidi beta (A+) et intracellularium proteini tau (T+)^[4]. Iconismi medici ope atrophia macroscopica cerebri indicat neurodegenerationem (N+), saepe loborum frontalium et temporalium velut hippocampi.

In morbi cursu morbus Alzheimer cum pluribus morbis aliis coniunctus queat^[5].

Die 21 Septembris est dies mundi morbi Alzheimerani.

Causae

Morbus Alzheimeranus est morbus hominis. Quo pacto affectus pathologici nascuntur et dein intus in cerebro crescunt nunc etiam inexplicatum permanent.

Ad causas explicandum tamen plures hypotheses pronuntiatae sunt, exempli gratia hypothesis cholinergica aut hypothesis amyloidorum aut hypothesis Tau. Etiam inflammatio in enumeratione causarum applicata est^[6]. Nonnulli vero casus morbi Alzheimeriani in commutationes geneticas reduci possunt.

Hypothesis cholinergica

Hac vetissima, ad quem pleraeque substantiae morbum Alzheimeranum medendi hodiernae referuntur, eum synthesi reducta neurotransmissoris cetylcholini explicari posse magnopere suggesta est. Quamquam haec hypothesis, cum facile intellegi possit, iam diu dubitationem attulit.

Architectura genetica

Increscunt argumenta, quae genetica morbi Alzheimerani in forum disputationum scientificorum proponunt. Iam non solum nonnullae mutationes in quibusdam familiis, sed etiam polymorphismi nucleotidi singularis^[7] genomi momenta processus morbi at protectiva^[8] habent.

Pathologia

In morbi cursu diversae structurae cerebrales affectae sunt, ut cortices cerebri, uterque hippocampus cum fornice.

Neuropathologia

Initium dicendi morbus Alzheimeranus de inopia neuronorum et synapsum eorum in quibusdam cerebri regionibus scribitur. Signum macropathologicum est atrophia earum. Post specialem colorationem sub microscopio dolosae structurae signa micropathologica oculis inspicientibus aperte positae sunt.

Distributio et cursus detrimentorum pathologicorum diversi sunt et per haec symptomata diversa explicantur^[9]: Apathia frequentius cum laesionibus cortice cingulari anteriore, at depressio cum detrimento lobo frontali superiore coniuncta est.

Pathobiochemica

Aggregatio proteinorum pathologicarum, imprimis in synapsibus, maius momentum habet^[10]. Etiam homeostasis et vectura mutata intracellularis elementi zinci detrimentose videtur ^[11].

Diagnosis

Adhuc variae societates scientificae criteria diagnostica morbi Alzheimeriani divulgaverunt. Secundum ICD-10 morbus Alzheimeranus est morbus neurologiae (G30); et dementia (F00) mutationibus intracerebralibus causa symptoma. Adhuc nonnulla etiam signa, in parte incerta, et e sanguine et ex liquore cerebrospinali nominantur^[12].

ICD-10: Dementia et morbus Alzheimerianus

Ante mortem diagnosis restat incerta. Symptomata sunt dementia, initium latens, progressus tardus. Non ad morbum Alzheimeranum attinent hemiparesis et initium apoplecticum, neque hypothyreosis, hydrocephalus, hypercalcaemia, haematoma subdurale.

Valores ex liquore cerebrospinali investigandae

Saepe investigari possunt valores haec subsequentes.^[13]

Aß(1-42)
proteinum tau
phospho-tau

Criteria NIA-AA

Anno 2011 Institutum Nationalis Senescendi (national Institute on aging, NIA) et Associatio Alzheimerianus (AA) criteria clinica morbi Alzheimerani divulgavit^[14]. Criteria NIA-AA morbi Alzheimeriani

probabilis dementia apud morbum Alzheimerianum,
possibilis dementia apud morbum Alzheimerianum,
dementia, probabiliter non morbo Alzheimeriano causato

definiunt. Anno 2018 idem grex operarius criteria scientifica cum indicatoribus biologicis, ad amyloidum beta (A), proteinum tau (T), et neurodegeneratioem (N) valentes, dedit^[15].

Criteria IWG-2

Anno 2014 grex operarius internationalis (IWG) et phaenotypos clinicos et signa biochimica connectens criteria morbi Alzheimerani divulgavit^[16]. Eventus separationem inter phaenotypum typicum et atypicum fuit.

Therapia

Sanatio morbi per medicamenta adhuc vix feliciter apparet. In tractandano symptomata quidem morbi Alzheimerani quaedam medicamenta excogitata sunt, quae interdum (false) antidementiva vocantur, sed lenimentum applicari possunt. Ea antidementiva dicta communiter sunt inhibitores enzymi acetylcholini esterasis. Hodie scientia medica effectus anticorporum diversorum investigat^[17]. Effectus antidepressivi escitaloprami incertus est. Suspicatur, ut alia antidepressiva quoque, velut bexarotenum (agonista receptorii retinoidi X), et etiam curcuminum substantia antiinflammatoria, forsitan effectus salubres exerceant^[18].

Anticorpora

Mense maio 2021 iterum grex scientificus reductionem macularum amyloido beta factarum, nunc ope anticorporis donanemabi, exposuerunt^[19] Eadem ratione aducanumab^[20]et bapineuzumab^[21] et gantenerumab^[22] fabrefacta sunt. Adhuc videtur, tamen, ut effectus clinici cognitionis effectibus reductionis macularum minores secuti sint. Praeterea effectus adversi eo in tempore ad differentiam therapeuticam addunt^[23].

Escitalopramum

Conferatur pagina principalis Escitalopramum.

Nuper effectus escitalopramum, inhibitoris reabsorptionis serotonini selectivi, effectibus escitaloprami apud mures divulgatis, disputatur^[24]. Videtur, ut etiam in hominibus reductio oneris amyloido beta facti observari potest, quamquam adhuc effectus clini incogniti sunt^[25].

Nexus interni

Notae

↑ "Dementia in morbo Alzheimer . . . praecox . . . tardiva [etc.]": vide F00-F09 apud Stetoskop
↑ Vel "morbus Alzheimerianus," in Tuomo Pekkanen, "De morbo Alzheimeriano," Nuntii Latini, 26 Iulii 2002.
↑ Knopman D. S., Petersen R. C., Jack C. R. Jr. (2019). "A brief history of "Alzheimer disease": Multiple meanings separated by a common name". Neurology 92 (22): 1053-9
↑ Bloom G. S. (Apr 2014). "Amyloid-β and tau: the trigger and bullet in Alzheimer disease pathogenesis". JAMA neurology 71 (4): 505-8
↑ Santiago J. A., Potashkin S. A. (Feb 2021). "The Impact of Disease Comorbidities in Alzheimer's Disease". Frontiers in ageing neuroscience
↑ Heneka M. T., Carson M. J., El Khoury J., et al. (2015). "Neuroinflammation in Alzheimer's Disease". The Lancet. Neurology 14 (4): 388-405 .
↑ Lee S. H., Harold D., Nyholt D. R. et al. (2013). "Estimation and partitioning of polygenic variation captured by common SNPs for Alzheimer's disease, multiple sclerosis and endometriosis". Humam molecular genetics 22 (4): 832-41
↑ Wolf A. B., Caselli R. J., Reiman E. M., Valla J. (2013). "APOE and neuroenergetics: an emerging paradigm in Alzheimer's disease". Neurobiology of aging 34 (4): 1007-17 .
↑ Chen Y., Dang M., Zhang Z. (Iun 2021). "Brain mechanisms underlying neuropsychiatric symptoms in Alzheimer's disease: a systematic review of symptom-general and -specific lesion patterns". Molecular neurodegeneration 16 (1): 38
↑ Hashimoto M., Rockenstein E., Crews L., Masliah E. (2003). "Role of protein aggregation in mitochondrial dysfunction and neurodegeneration in Alzheimer's and Parkinson's diseases". Neuromolecular medicine 4 (1-2): 21-36
↑ Xu Y., Xiao G., Liu L., Lang M. (Dec 2019). "Zinc transporters in Alzheimer's disease". Molecular brain 12 (1): 10.1186/s13041-019-0528-2 .
↑ Olsson B., Lautner R., Andreasson U., Öhrfelt A., Portelius E., Bjerke M., Hölttä M., Rosén C., Olsson C., Strobel G., Wu E., Dakin K., Petzold M., Blennow K., Zetterberg H. (2016). "CSF and blood biomarkers for the diagnosis of Alzheimer's disease: a systematic review and meta-analysis". The Lancet. Neurology 15 (7): 673-84 .
↑ Jack C. R. Jr., Bennett D. A., Blennow K., Carrillo M. C., Dunn B., Haeberlein S. B., Holtzman D. M., Jagust W., Jessen F., et al. (2018). "NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease". Alzheimer's & dementia 14 (4): 535-62
↑ McKhann G. M., Knopman D. S., et al. (Mai 2011). "The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease". Alzheimer & dementia 7 (3): 263-9 .
↑ Jack C. R. Jr., Bennett D. A. (Apr 2018). "NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease". Alzheimer & dementia 14 (4): 535-62 .
↑ Dubois B., Feldman H. H., et al. (Iun 2014). "Advancing research diagnostic criteria for Alzheimer's disease: the IWG-2 criteria". The Lancet. Neurology 13 (6): 614-29 .
↑ Tolar M., Abushakra S., Hey J. A., Porsteinsson A., Sabbagh M. (Aug 2020). "Aducanumab, gantenerumab, BAN2401, and ALZ-801-the first wave of amyloid-targeting drugs for Alzheimer's disease with potential for near term approval". Alzheimer's research & therapy 12 (1): 95
↑ Miziak B., .Błaszczyk B., Czuczwar S. L. (Mai 2021). "Some Candidate Drugs for Pharmacotherapy of Alzheimer's Disease". Pharmaceuticals 14 (5): 458
↑ Mintun M. A., Lo A. C., Evans C. D., Wessels A. M., Ardayfio P. A., Andersen S. W., Shcherbinin S., Sparks J., Sims J. R., Brys M., Apostolova L. G., Salloway S. P., Skovronsky D. M. (Mar 2021). "Donanemab in Early Alzheimer's Disease". New England Journal of Medicine 384 (18): 1691-704
↑ Sevigny J., Chiao P., Bussière T., Weinreb P. H., Williams L., Maier M., Dunstan R., Salloway S., Chen T., Ling Y., O'Gorman J., Qian F., Arastu M., Li M., Chollate S., Brennan M. S., Quintero-Monzon O., Scannevin R. H., Arnold H. M., Engber T., Rhodes K., Ferrero J., Hang Y., Mikulskis A., Grimm J., Hock C., Nitsch R. M., Sandrock A. (Sep 2016). "The antibody aducanumab reduces Aβ plaques in Alzheimer's disease". Nature 537 (7618): 50-6
↑ Abushouk A. I., Elmaraezy A., Aglan A., Salama R., Fouda S., Fouda R., AlSafadi A. M. (Apr 2017). "Bapineuzumab for mild to moderate Alzheimer's disease: a meta-analysis of randomized controlled trials". BMC neurology 17 (1): 66
↑ Klein G., Delmar P., Voyle N., Rehal S., Hofmann C., Abi-Saab D., Andjelkovic M., Ristic S., Wang G., Bateman R., Kerchner G. A., Baudler M., Fontoura P., Doody R. (Dec 2019). "Gantenerumab reduces amyloid-β plaques in patients with prodromal to moderate Alzheimer's disease: a PET substudy interim analysis". Alzheimer's research & therapy 11 (1): 101
↑ Toyn J. (Mai 2015). "What lessons can be learned from failed Alzheimer's disease trials?". Expert review of clinical pharmacology 8 (3): 267-9
↑ Cirrito J. R., Wallace C. E., Yan P., Davis T. A., Gardiner W. D., Doherty B. M., King D., Yuede C. M., Lee J.-M., Sheline Y. I. (Nov 2020). "Effect of escitalopram on Aβ levels and plaque load in an Alzheimer mouse model". Neurolgy 95 (19): e2666-e2674
↑ Sheline Y. I., Snider B. J., Beer J. C., Seok D., Fagan A. M., Suckow R. F., Lee J.-M., Waligorska T., Korecka M., Aselcioglu I., Morris J. C., Shaw L. M., Cirrito J. R. (2020). "Effect of escitalopram dose and treatment duration on CSF Aβ levels in healthy older adults: A controlled clinical trial". Neurology 95 (19): e2658-e2665

Bibliographia

Alzheimer's Disease: Unraveling the Mystery. US Department of Health and Human Services, National Institute on Aging, NIH. 2008
Can Alzheimer's Disease Be Prevented?. US Department of Health and Human Services, National Institute on Aging, NIH. 2009
Caring for a Person with Alzheimer's Disease: Your Easy-to-Use Guide from the National Institute on Aging. US Department of Health and Human Services, National Institute on Aging, NIH. 2009
Cummings, J. L., J. C. Frank, D. Cherry, N. D. Kohatsu, B. Kemp, L. Hewett, et B. Mittman. 2002. Guidelines for managing Alzheimer's disease: Part I: Assessment. American Family Physician 65(11):2263–2272. pmid 12074525.
Cummings, J. L., J. C. Frank, D. Cherry, N. D. Kohatsu, B. Kemp, L. Hewett, et B. Mittman. 2002. Guidelines for managing Alzheimer's disease: Part II: Treatment. American Family Physician 65(12):2525–2534. pmid=12086242.
Russell, D., S. Barston, et M. White (19 Decembris 2007). "Alzheimer's Behavior Management: Learn to manage common behavior problems". helpguide.org

Nexus externi

Vicimedia Communia plura habent quae ad morbum Alzheimerianum spectant.

"Cognitive Test for Alzheimer's". NLM video (Anglice)
"Healthy aging" (Anglice)
Alzheimer's Disease Research Centers, www.nia.nih.gov (National Institute of Aging)
Alzheimer's Disease Education and Referral (ADEAR) Center, www.nia.nih.gov (National Institute of Aging)
Alzheimer's Association, www.alz.org (Alzheimer's Association)
UCSF Memory and Aging Center, memory.ucsf.edu (University of California San Francisco)

stipula

Haec stipula ad medicinam spectat. Amplifica, si potes!

[1] "Dementia in morbo Alzheimer . . . praecox . . . tardiva [etc.]": vide F00-F09 apud Stetoskop

[2] Vel "morbus Alzheimerianus," in Tuomo Pekkanen, "De morbo Alzheimeriano," Nuntii Latini, 26 Iulii 2002.

[3] Knopman D. S., Petersen R. C., Jack C. R. Jr. (2019). "A brief history of "Alzheimer disease": Multiple meanings separated by a common name". Neurology 92 (22): 1053-9

[4] Bloom G. S. (Apr 2014). "Amyloid-β and tau: the trigger and bullet in Alzheimer disease pathogenesis". JAMA neurology 71 (4): 505-8

[5] Santiago J. A., Potashkin S. A. (Feb 2021). "The Impact of Disease Comorbidities in Alzheimer's Disease". Frontiers in ageing neuroscience

[6] Heneka M. T., Carson M. J., El Khoury J., et al. (2015). "Neuroinflammation in Alzheimer's Disease". The Lancet. Neurology 14 (4): 388-405 .

[7] Lee S. H., Harold D., Nyholt D. R. et al. (2013). "Estimation and partitioning of polygenic variation captured by common SNPs for Alzheimer's disease, multiple sclerosis and endometriosis". Humam molecular genetics 22 (4): 832-41

[8] Wolf A. B., Caselli R. J., Reiman E. M., Valla J. (2013). "APOE and neuroenergetics: an emerging paradigm in Alzheimer's disease". Neurobiology of aging 34 (4): 1007-17 .

[9] Chen Y., Dang M., Zhang Z. (Iun 2021). "Brain mechanisms underlying neuropsychiatric symptoms in Alzheimer's disease: a systematic review of symptom-general and -specific lesion patterns". Molecular neurodegeneration 16 (1): 38

[10] Hashimoto M., Rockenstein E., Crews L., Masliah E. (2003). "Role of protein aggregation in mitochondrial dysfunction and neurodegeneration in Alzheimer's and Parkinson's diseases". Neuromolecular medicine 4 (1-2): 21-36

[11] Xu Y., Xiao G., Liu L., Lang M. (Dec 2019). "Zinc transporters in Alzheimer's disease". Molecular brain 12 (1): 10.1186/s13041-019-0528-2 .

[12] Olsson B., Lautner R., Andreasson U., Öhrfelt A., Portelius E., Bjerke M., Hölttä M., Rosén C., Olsson C., Strobel G., Wu E., Dakin K., Petzold M., Blennow K., Zetterberg H. (2016). "CSF and blood biomarkers for the diagnosis of Alzheimer's disease: a systematic review and meta-analysis". The Lancet. Neurology 15 (7): 673-84 .

[13] Jack C. R. Jr., Bennett D. A., Blennow K., Carrillo M. C., Dunn B., Haeberlein S. B., Holtzman D. M., Jagust W., Jessen F., et al. (2018). "NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease". Alzheimer's & dementia 14 (4): 535-62

[14] McKhann G. M., Knopman D. S., et al. (Mai 2011). "The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease". Alzheimer & dementia 7 (3): 263-9 .

[15] Jack C. R. Jr., Bennett D. A. (Apr 2018). "NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease". Alzheimer & dementia 14 (4): 535-62 .

[16] Dubois B., Feldman H. H., et al. (Iun 2014). "Advancing research diagnostic criteria for Alzheimer's disease: the IWG-2 criteria". The Lancet. Neurology 13 (6): 614-29 .

[17] Tolar M., Abushakra S., Hey J. A., Porsteinsson A., Sabbagh M. (Aug 2020). "Aducanumab, gantenerumab, BAN2401, and ALZ-801-the first wave of amyloid-targeting drugs for Alzheimer's disease with potential for near term approval". Alzheimer's research & therapy 12 (1): 95

[18] Miziak B., .Błaszczyk B., Czuczwar S. L. (Mai 2021). "Some Candidate Drugs for Pharmacotherapy of Alzheimer's Disease". Pharmaceuticals 14 (5): 458

[19] Mintun M. A., Lo A. C., Evans C. D., Wessels A. M., Ardayfio P. A., Andersen S. W., Shcherbinin S., Sparks J., Sims J. R., Brys M., Apostolova L. G., Salloway S. P., Skovronsky D. M. (Mar 2021). "Donanemab in Early Alzheimer's Disease". New England Journal of Medicine 384 (18): 1691-704

[20] Sevigny J., Chiao P., Bussière T., Weinreb P. H., Williams L., Maier M., Dunstan R., Salloway S., Chen T., Ling Y., O'Gorman J., Qian F., Arastu M., Li M., Chollate S., Brennan M. S., Quintero-Monzon O., Scannevin R. H., Arnold H. M., Engber T., Rhodes K., Ferrero J., Hang Y., Mikulskis A., Grimm J., Hock C., Nitsch R. M., Sandrock A. (Sep 2016). "The antibody aducanumab reduces Aβ plaques in Alzheimer's disease". Nature 537 (7618): 50-6

[21] Abushouk A. I., Elmaraezy A., Aglan A., Salama R., Fouda S., Fouda R., AlSafadi A. M. (Apr 2017). "Bapineuzumab for mild to moderate Alzheimer's disease: a meta-analysis of randomized controlled trials". BMC neurology 17 (1): 66

[22] Klein G., Delmar P., Voyle N., Rehal S., Hofmann C., Abi-Saab D., Andjelkovic M., Ristic S., Wang G., Bateman R., Kerchner G. A., Baudler M., Fontoura P., Doody R. (Dec 2019). "Gantenerumab reduces amyloid-β plaques in patients with prodromal to moderate Alzheimer's disease: a PET substudy interim analysis". Alzheimer's research & therapy 11 (1): 101

[23] Toyn J. (Mai 2015). "What lessons can be learned from failed Alzheimer's disease trials?". Expert review of clinical pharmacology 8 (3): 267-9

[24] Cirrito J. R., Wallace C. E., Yan P., Davis T. A., Gardiner W. D., Doherty B. M., King D., Yuede C. M., Lee J.-M., Sheline Y. I. (Nov 2020). "Effect of escitalopram on Aβ levels and plaque load in an Alzheimer mouse model". Neurolgy 95 (19): e2666-e2674

[25] Sheline Y. I., Snider B. J., Beer J. C., Seok D., Fagan A. M., Suckow R. F., Lee J.-M., Waligorska T., Korecka M., Aselcioglu I., Morris J. C., Shaw L. M., Cirrito J. R. (2020). "Effect of escitalopram dose and treatment duration on CSF Aβ levels in healthy older adults: A controlled clinical trial". Neurology 95 (19): e2658-e2665

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