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  • 1. Feigin, Valery L.
    et al.
    Nichols, Emma
    Alam, Tahiya
    Bannick, Marlena S.
    Beghi, Ettore
    Blake, Natacha
    Culpepper, William J.
    Dorsey, E. Ray
    Elbaz, Alexis
    Ellenbogen, Richard G.
    Fisher, James L.
    Fitzmaurice, Christina
    Giussani, Giorgia
    Glennie, Linda
    James, Spencer L.
    Johnson, Catherine Owens
    Kassebaum, Nicholas J.
    Logroscino, Giancarlo
    Marin, Benoit
    Mountjoy-Venning, W. Cliff
    Nguyen, Minh
    Ofori-Asenso, Richard
    Patel, Anoop P.
    Piccininni, Marco
    Roth, Gregory A.
    Steiner, Timothy J.
    Stovner, Lars Jacob
    Szoeke, Cassandra E. I.
    Theadom, Alice
    Vollset, Stein Emil
    Wallin, Mitchell Taylor
    Wright, Claire
    Zunt, Joseph Raymond
    Abbasi, Nooshin
    Abd-Allah, Foad
    Abdelalim, Ahmed
    Abdollahpour, Ibrahim
    Aboyans, Victor
    Abraha, Haftom Niguse
    Acharya, Dilaram
    Adamu, Abdu A.
    Adebayo, Oladimeji M.
    Adeoye, Abiodun Moshood
    Adsuar, Jose C.
    Afarideh, Mohsen
    Agrawal, Sutapa
    Ahmadi, Alireza
    Ahmed, Muktar Beshir
    Aichour, Amani Nidhal
    Aichour, Ibtihel
    Aichour, Miloud Taki Eddine
    Akinyemi, Rufus Olusola
    Akseer, Nadia
    Al-Eyadhy, Ayman
    Salman, Rustam Al-Shahi
    Alahdab, Fares
    Alene, Kefyalew Addis
    Aljunid, Syed Mohamed
    Altirkawi, Khalid
    Alvis-Guzman, Nelson
    Anber, Nahla Hamed
    Antonio, Carl Abelardo T.
    Arabloo, Jalal
    Aremu, Olatunde
    Arnlov, Johan
    Asayesh, Hamid
    Asghar, Rana Jawad
    Atalay, Hagos Tasew
    Awasthi, Ashish
    Ayala Quintanilla, Beatriz Paulina
    Ayuk, Tambe B.
    Badawi, Alaa
    Banach, Maciej
    Banoub, Joseph Adel Mattar
    Barboza, Miguel A.
    Barker-Collo, Suzanne Lyn
    Barnighausen, Till Winfried
    Baune, Bernhard T.
    Bedi, Neeraj
    Behzadifar, Masoud
    Behzadifar, Meysam
    Bejot, Yannick
    Bekele, Bayu Begashaw
    Belachew, Abate Bekele
    Bennett, Derrick A.
    Bensenor, Isabela M.
    Berhane, Adugnaw
    Beuran, Mircea
    Bhattacharyya, Krittika
    Bhutta, Zulfiqar A.
    Biadgo, Belete
    Bijani, Ali
    Bililign, Nigus
    Bin Sayeed, Muhammad Shahdaat
    Blazes, Christopher Kynrint
    Brayne, Carol
    Butt, Zahid A.
    Campos-Nonato, Ismael R.
    Cantu-Brito, Carlos
    Car, Mate
    Cardenas, Rosario
    Carrero, Juan J.
    Carvalho, Felix
    Castaneda-Orjuela, Carlos A.
    Castro, Franz
    Catala-Lopez, Ferran
    Cerin, Ester
    Chaiah, Yazan
    Chang, Jung-Chen
    Chatziralli, Irini
    Chiang, Peggy Pei-Chia
    Christensen, Hanne
    Christopher, Devasahayam J.
    Cooper, Cyrus
    Cortesi, Paolo Angelo
    Costa, Vera M.
    Criqui, Michael H.
    Crowe, Christopher Stephen
    Damasceno, Albertino Antonio Moura
    Daryani, Ahmad
    De la Cruz-Gongora, Vanessa
    Pio De la Hoz, Fernando
    De Leo, Diego
    Degefa, Meaza Girma
    Demoz, Gebre Teklemariam
    Deribe, Kebede
    Dharmaratne, Samath Dhamminda
    Diaz, Daniel
    Dinberu, Mesfin Tadese
    Djalalinia, Shirin
    Doku, David Teye
    Dubey, Manisha
    Dubljanin, Eleonora
    Duken, Eyasu Ejeta
    Edvardsson, David
    Umeå University, Faculty of Medicine, Department of Nursing.
    El-Khatib, Ziad
    Endres, Matthias
    Endries, Aman Yesuf
    Eskandarieh, Sharareh
    Esteghamati, Alireza
    Esteghamati, Sadaf
    Farhadi, Farzaneh
    Faro, Andre
    Farzadfar, Farshad
    Farzaei, Mohammad Hosein
    Fatima, Batool
    Fereshtehnejad, Seyed-Mohammad
    Fernandes, Eduarda
    Feyissa, Garumma Tolu
    Filip, Irina
    Fischer, Florian
    Fukumoto, Takeshi
    Ganji, Morsaleh
    Gankpe, Fortune Gbetoho
    Garcia-Gordillo, Miguel A.
    Gebre, Abadi Kahsu
    Gebremichael, Teklu Gebrehiwo
    Gelaw, Belayneh K.
    Geleijnse, Johanna M.
    Geremew, Demeke
    Gezae, Kebede Embaye
    Ghasemi-Kasman, Maryam
    Gidey, Mahari Y.
    Gill, Paramjit Singh
    Gill, Tiffany K.
    Gnedovskaya, Elena V.
    Goulart, Alessandra C.
    Grada, Ayman
    Grosso, Giuseppe
    Guo, Yuming
    Gupta, Rahul
    Gupta, Rajeev
    Haagsma, Juanita A.
    Hagos, Tekleberhan B.
    Haj-Mirzaian, Arvin
    Haj-Mirzaian, Arya
    Hamadeh, Randah R.
    Hamidi, Samer
    Hankey, Graeme J.
    Hao, Yuantao
    Haro, Josep Maria
    Hassankhani, Hadi
    Hassen, Hamid Yimam
    Havmoeller, Rasmus
    Hay, Simon I.
    Hegazy, Mohamed I.
    Heidari, Behnam
    Henok, Andualem
    Heydarpour, Fatemeh
    Hoang, Chi Linh
    Hole, Michael K.
    Rad, Enayatollah Homaie
    Hosseini, Seyed Mostafa
    Hu, Guoqing
    Igumbor, Ehimario U.
    Ilesanmi, Olayinka Stephen
    Irvani, Seyed Sina Naghibi
    Islam, Sheikh Mohammed Shariful
    Jakovljevic, Mihajlo
    Javanbakht, Mehdi
    Jha, Ravi Prakash
    Jobanputra, Yash B.
    Jonas, Jost B.
    Jozwiak, Jacek Jerzy
    Jurisson, Mikk
    Kahsay, Amaha
    Kalani, Rizwan
    Kalkonde, Yogeshwar
    Kamil, Teshome Abegaz
    Kanchan, Tanuj
    Karami, Manoochehr
    Karch, Andre
    Karimi, Narges
    Kasaeian, Amir
    Kassa, Tesfaye Dessale
    Kassa, Zemenu Yohannes
    Kaul, Anil
    Kefale, Adane Teshome
    Keiyoro, Peter Njenga
    Khader, Yousef Saleh
    Khafaie, Morteza Abdullatif
    Khalil, Ibrahim A.
    Khan, Ejaz Ahmad
    Khang, Young-Ho
    Khazaie, Habibolah
    Kiadaliri, Aliasghar A.
    Kiirithio, Daniel N.
    Kim, Anthony S.
    Kim, Daniel
    Kim, Young-Eun
    Kim, Yun Jin
    Kisa, Adnan
    Kokubo, Yoshihiro
    Koyanagi, Ai
    Krishnamurthi, Rita V.
    Defo, Barthelemy Kuate
    Bicer, Burcu Kucuk
    Kumar, Manasi
    Lacey, Ben
    Lafranconi, Alessandra
    Lansingh, Van C.
    Latifi, Arman
    Leshargie, Cheru Tesema
    Li, Shanshan
    Liao, Yu
    Linn, Shai
    Lo, Warren David
    Lopez, Jaifred Christian F.
    Lorkowski, Stefan
    Lotufo, Paulo A.
    Lucas, Robyn M.
    Lunevicius, Raimundas
    Mackay, Mark T.
    Mahotra, Narayan Bahadur
    Majdan, Marek
    Majdzadeh, Reza
    Majeed, Azeem
    Malekzadeh, Reza
    Malta, Deborah Carvalho
    Manafi, Navid
    Mansournia, Mohammad Ali
    Mantovani, Lorenzo Giovanni
    Marz, Winfried
    Mashamba-Thompson, Tivani Phosa
    Massenburg, Benjamin Ballard
    Mate, Kedar K. V.
    McAlinden, Colm
    McGrath, John J.
    Mehta, Varshil
    Meier, Toni
    Meles, Hagazi Gebre
    Melese, Addisu
    Memiah, Peter T. N.
    Memish, Ziad A.
    Mendoza, Walter
    Mengistu, Desalegn Tadese
    Mengistu, Getnet
    Meretoja, Atte
    Meretoja, Tuomo J.
    Mestrovic, Tomislav
    Miazgowski, Bartosz
    Miazgowski, Tomasz
    Miller, Ted R.
    Mini, G. K.
    Mirrakhimov, Erkin M.
    Moazen, Babak
    Mohajer, Bahram
    Mezerji, Naser Mohammad Gholi
    Mohammadi, Moslem
    Mohammadi-Khanaposhtani, Maryam
    Mohammadibakhsh, Roghayeh
    Mohammadnia-Afrouzi, Mousa
    Mohammed, Shafiu
    Mohebi, Farnam
    Mokdad, Ali H.
    Monasta, Lorenzo
    Mondello, Stefania
    Moodley, Yoshan
    Moosazadeh, Mahmood
    Moradi, Ghobad
    Moradi-Lakeh, Maziar
    Moradinazar, Mehdi
    Moraga, Paula
    Velasquez, Ilais Moreno
    Morrison, Shane Douglas
    Mousavi, Seyyed Meysam
    Muhammed, Oumer Sada
    Muruet, Walter
    Musa, Kamarul Imran
    Mustafa, Ghulam
    Naderi, Mehdi
    Nagel, Gabriele
    Naheed, Aliya
    Naik, Gurudatta
    Najafi, Farid
    Nangia, Vinay
    Negoi, Ionut
    Negoi, Ruxandra Irina
    Newton, Charles Richard James
    Ngunjiri, Josephine W.
    Nguyen, Cuong Tat
    Nguyen, Long Hoang
    Ningrum, Dina Nur Anggraini
    Nirayo, Yirga Legesse
    Nixon, Molly R.
    Norrving, Bo
    Noubiap, Jean Jacques
    Shiadeh, Malihe Nourollahpour
    Nyasulu, Peter S.
    Ogbo, Felix Akpojene
    Oh, In-Hwan
    Olagunju, Andrew T.
    Olagunju, Tinuke O.
    Olivares, Pedro R.
    Onwujekwe, Obinna E.
    Oren, Eyal
    Owolabi, Mayowa Ojo
    Mahesh, P. A.
    Pakpour, Amir H.
    Pan, Wen-Harn
    Panda-Jonas, Songhomitra
    Pandian, Jeyaraj Durai
    Patel, Sangram Kishor
    Pereira, David M.
    Petzold, Max
    Pillay, Julian David
    Piradov, Michael A.
    Polanczyk, Guilherme V.
    Polinder, Suzanne
    Postma, Maarten J.
    Poulton, Richie
    Poustchi, Hossein
    Prakash, Swayam
    Prakash, V.
    Qorbani, Mostafa
    Radfar, Amir
    Rafay, Anwar
    Rafiei, Alireza
    Rahim, Fakher
    Rahimi-Movaghar, Vafa
    Rahman, Mahfuzar
    Rahman, Mohammad Hifz Ur
    Rahman, Muhammad Aziz
    Rajati, Fatemeh
    Ram, Usha
    Ranta, Anna
    Rawaf, David Laith
    Rawaf, Salman
    Reinig, Nickolas
    Reis, Cesar
    Renzaho, Andre M. N.
    Resnikoff, Serge
    Rezaeian, Shahab
    Rezai, Mohammad Sadegh
    Gonzalez, Carlos Miguel Rios
    Roberts, Nicholas L. S.
    Roever, Leonardo
    Ronfani, Luca
    Roro, Elias Merdassa
    Roshandel, Gholamreza
    Rostami, Ali
    Sabbagh, Parisa
    Sacco, Ralph L.
    Sachdev, Perminder S.
    Saddik, Basema
    Safari, Hosein
    Safari-Faramani, Roya
    Safi, Sare
    Safiri, Saeid
    Sagar, Rajesh
    Sahathevan, Ramesh
    Sahebkar, Amirhossein
    Sahraian, Mohammad Ali
    Salamati, Payman
    Zahabi, Saleh Salehi
    Salimi, Yahya
    Samy, Abdallah M.
    Sanabria, Juan
    Santos, Itamar S.
    Milicevic, Milena M. Santric
    Sarrafzadegan, Nizal
    Sartorius, Benn
    Sarvi, Shahabeddin
    Sathian, Brijesh
    Satpathy, Maheswar
    Sawant, Arundhati R.
    Sawhney, Monika
    Schneider, Ione J. C.
    Schottker, Ben
    Schwebel, David C.
    Seedat, Soraya
    Sepanlou, Sadaf G.
    Shabaninejad, Hosein
    Shafieesabet, Azadeh
    Shaikh, Masood Ali
    Shakir, Raad A.
    Shams-Beyranvand, Mehran
    Shamsizadeh, Morteza
    Sharif, Mehdi
    Sharif-Alhoseini, Mahdi
    She, Jun
    Sheikh, Aziz
    Sheth, Kevin N.
    Shigematsu, Mika
    Shiri, Rahman
    Shirkoohi, Reza
    Shiue, Ivy
    Siabani, Soraya
    Siddiqi, Tariq J.
    Sigfusdottir, Inga Dora
    Sigurvinsdottir, Rannveig
    Silberberg, Donald H.
    Silva, Joao Pedro
    Silveira, Dayane Gabriele Alves
    Singh, Jasvinder A.
    Sinha, Dhirendra Narain
    Skiadaresi, Eirini
    Smith, Mari
    Sobaih, Badr Hasan
    Sobhani, Soheila
    Soofi, Moslem
    Soyiri, Ireneous N.
    Sposato, Luciano A.
    Stein, Dan J.
    Stein, Murray B.
    Stokes, Mark A.
    Sufiyan, Mu'awiyyah Babale
    Sykes, Bryan L.
    Sylaja, Pn
    Tabares-Seisdedos, Rafael
    Ao, Braden James Te
    Tehrani-Banihashemi, Arash
    Temsah, Mohamad-Hani
    Temsah, Omar
    Thakur, Jarnail Singh
    Thrift, Amanda G.
    Topor-Madry, Roman
    Tortajada-Girbes, Miguel
    Tovani-Palone, Marcos Roberto
    Tran, Bach Xuan
    Tran, Khanh Bao
    Truelsen, Thomas Clement
    Tsadik, Afewerki Gebremeskel
    Car, Lorainne Tudor
    Ukwaja, Kingsley Nnanna
    Ullah, Irfan
    Usman, Muhammad Shariq
    Uthman, Olalekan A.
    Valdez, Pascual R.
    Vasankari, Tommi Juhani
    Vasanthan, Rajagopalan
    Veisani, Yousef
    Venketasubramanian, Narayanaswamy
    Violante, Francesco S.
    Vlassov, Vasily
    Vosoughi, Kia
    Vu, Giang Thu
    Vujcic, Isidora S.
    Wagnew, Fasil Shiferaw
    Waheed, Yasir
    Wang, Yuan-Pang
    Weiderpass, Elisabete
    Weiss, Jordan
    Whiteford, Harvey A.
    Wijeratne, Tissa
    Winkler, Andrea Sylvia
    Wiysonge, Charles Shey
    Wolfe, Charles D. A.
    Xu, Gelin
    Yadollahpour, Ali
    Yamada, Tomohide
    Yano, Yuichiro
    Yaseri, Mehdi
    Yatsuya, Hiroshi
    Yimer, Ebrahim M.
    Yip, Paul
    Yisma, Engida
    Yonemoto, Naohiro
    Yousefifard, Mahmoud
    Yu, Chuanhua
    Zaidi, Zoubida
    Bin Zaman, Sojib
    Zamani, Mohammad
    Zandian, Hamed
    Zare, Zohreh
    Zhang, Yunquan
    Zodpey, Sanjay
    Naghavi, Mohsen
    Murray, Christopher J. L.
    Vos, Theo
    Global, regional, and national burden of neurological disorders, 1990–2016: a systematic analysis for the Global Burden of Disease Study 20162019In: Lancet Neurology, ISSN 1474-4422, E-ISSN 1474-4465, Vol. 18, no 5, p. 459-480Article in journal (Refereed)
    Abstract [en]

    Background: Neurological disorders are increasingly recognised as major causes of death and disability worldwide. The aim of this analysis from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 is to provide the most comprehensive and up-to-date estimates of the global, regional, and national burden from neurological disorders.

    Methods: We estimated prevalence, incidence, deaths, and disability-adjusted life-years (DALYs; the sum of years of life lost [YLLs] and years lived with disability [YLDs]) by age and sex for 15 neurological disorder categories (tetanus, meningitis, encephalitis, stroke, brain and other CNS cancers, traumatic brain injury, spinal cord injury, Alzheimer's disease and other dementias, Parkinson's disease, multiple sclerosis, motor neuron diseases, idiopathic epilepsy, migraine, tension-type headache, and a residual category for other less common neurological disorders) in 195 countries from 1990 to 2016. DisMod-MR 2.1, a Bayesian meta-regression tool, was the main method of estimation of prevalence and incidence, and the Cause of Death Ensemble model (CODEm) was used for mortality estimation. We quantified the contribution of 84 risks and combinations of risk to the disease estimates for the 15 neurological disorder categories using the GBD comparative risk assessment approach.

    Findings: Globally, in 2016, neurological disorders were the leading cause of DALYs (276 million [95% UI 247–308]) and second leading cause of deaths (9·0 million [8·8–9·4]). The absolute number of deaths and DALYs from all neurological disorders combined increased (deaths by 39% [34–44] and DALYs by 15% [9–21]) whereas their age-standardised rates decreased (deaths by 28% [26–30] and DALYs by 27% [24–31]) between 1990 and 2016. The only neurological disorders that had a decrease in rates and absolute numbers of deaths and DALYs were tetanus, meningitis, and encephalitis. The four largest contributors of neurological DALYs were stroke (42·2% [38·6–46·1]), migraine (16·3% [11·7–20·8]), Alzheimer's and other dementias (10·4% [9·0–12·1]), and meningitis (7·9% [6·6–10·4]). For the combined neurological disorders, age-standardised DALY rates were significantly higher in males than in females (male-to-female ratio 1·12 [1·05–1·20]), but migraine, multiple sclerosis, and tension-type headache were more common and caused more burden in females, with male-to-female ratios of less than 0·7. The 84 risks quantified in GBD explain less than 10% of neurological disorder DALY burdens, except stroke, for which 88·8% (86·5–90·9) of DALYs are attributable to risk factors, and to a lesser extent Alzheimer's disease and other dementias (22·3% [11·8–35·1] of DALYs are risk attributable) and idiopathic epilepsy (14·1% [10·8–17·5] of DALYs are risk attributable).

    Interpretation: Globally, the burden of neurological disorders, as measured by the absolute number of DALYs, continues to increase. As populations are growing and ageing, and the prevalence of major disabling neurological disorders steeply increases with age, governments will face increasing demand for treatment, rehabilitation, and support services for neurological disorders. The scarcity of established modifiable risks for most of the neurological burden demonstrates that new knowledge is required to develop effective prevention and treatment strategies.

    Funding: Bill & Melinda Gates Foundation.

  • 2.
    Nelson, Peter T.
    et al.
    Univ Kentucky, 311 Sanders Brown Ctr Aging, Lexington, KY 40536 USA.
    Dickson, Dennis W.
    Mayo Clin, Jacksonville, FL 32224 USA.
    Trojanowski, John Q.
    Univ Penn, Philadelphia, PA 19104 USA.
    Jack, Clifford R., Jr.
    Mayo Clin, Rochester, MN USA.
    Boyle, Patricia A.
    Rush Univ, Med Ctr, Chicago, IL 60612 USA.
    Arfanakis, Konstantinos
    Rush Univ, Med Ctr, Chicago, IL 60612 USA;IIT, Chicago, IL 60616 USA.
    Rademakers, Rosa
    Mayo Clin, Jacksonville, FL 32224 USA.
    Alafuzoff, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Attems, Johannes
    Newcastle Univ, Newcastle Upon Tyne, Tyne & Wear, England.
    Brayne, Carol
    Univ Cambridge, Cambridge, England.
    Coyle-Gilchrist, Ian T. S.
    Univ Cambridge, Cambridge, England.
    Chui, Helena C.
    Univ Southern Calif, Los Angeles, CA USA.
    Fardo, David W.
    Univ Kentucky, 311 Sanders Brown Ctr Aging, Lexington, KY 40536 USA.
    Flanagan, Margaret E.
    Univ Minnesota, Minneapolis, MN USA.
    Halliday, Glenda
    Univ Sydney, Brain & Mind Ctr, Sydney, NSW, Australia;Cent Clin Sch, Fac Med & Hlth, Sydney, NSW, Australia.
    Hokkanen, Suvi R. K.
    Univ Cambridge, Cambridge, England.
    Hunter, Sally
    Univ Cambridge, Cambridge, England.
    Jicha, Gregory A.
    Univ Kentucky, 311 Sanders Brown Ctr Aging, Lexington, KY 40536 USA.
    Katsumata, Yuriko
    Univ Kentucky, 311 Sanders Brown Ctr Aging, Lexington, KY 40536 USA.
    Kawas, Claudia H.
    Univ Calif Irvine, Irvine, CA USA.
    Keene, C. Dirk
    Univ Washington, Seattle, WA 98195 USA.
    Kovacs, Gabor G.
    Med Univ Vienna, Inst Neurol, Vienna, Austria.
    Kukull, Walter A.
    Univ Washington, Seattle, WA 98195 USA.
    Levey, Allan I.
    Emory Univ, Atlanta, GA 30322 USA.
    Makkinejad, Nazanin
    IIT, Chicago, IL 60616 USA.
    Montine, Thomas J.
    Stanford Univ, Stanford, CA 94305 USA.
    Murayama, Shigeo
    Tokyo Metropolitan Geriatr Hosp, Tokyo, Japan;Inst Gerontol, Tokyo, Japan.
    Murray, Melissa E.
    Mayo Clin, Jacksonville, FL 32224 USA.
    Nag, Sukriti
    Rush Univ, Med Ctr, Chicago, IL 60612 USA.
    Rissman, Robert A.
    Univ Calif San Diego, San Diego, CA 92103 USA;Harvard Univ, Cambridge, MA 02138 USA.
    Seeley, William W.
    Univ Calif San Francisco, San Francisco, CA 94143 USA.
    Sperling, Reisa A.
    White, Charles L., III
    Univ Texas Southwestern Med Ctr Dallas, Dallas, TX 75390 USA.
    Yu, Lei
    Rush Univ, Med Ctr, Chicago, IL 60612 USA.
    Schneider, Julie A.
    Rush Univ, Med Ctr, Chicago, IL 60612 USA.
    Limbic-predominant age-related TDP-43 encephalopathy (LATE): consensus working group report2019In: Brain, ISSN 0006-8950, E-ISSN 1460-2156, Vol. 142, p. 1503-1527Article, review/survey (Refereed)
    Abstract [en]

    We describe a recently recognized disease entity, limbic-predominant age-related TDP-43 encephalopathy (LATE). LATE neuropathological change (LATE-NC) is defined by a stereotypical TDP-43 proteinopathy in older adults, with or without coexisting hippocampal sclerosis pathology. LATE-NC is a common TDP-43 proteinopathy, associated with an amnestic dementia syndrome that mimicked Alzheimer's-type dementia in retrospective autopsy studies. LATE is distinguished from frontotemporal lobar degeneration with TDP-43 pathology based on its epidemiology (LATE generally affects older subjects), and relatively restricted neuroanatomical distribution of TDP-43 proteinopathy. In community-based autopsy cohorts, similar to 25% of brains had sufficient burden of LATE-NC to be associated with discernible cognitive impairment. Many subjects with LATE-NC have comorbid brain pathologies, often including amyloid-beta plaques and tauopathy. Given that the oldest-old' are at greatest risk for LATE-NC, and subjects of advanced age constitute a rapidly growing demographic group in many countries, LATE has an expanding but under-recognized impact on public health. For these reasons, a working group was convened to develop diagnostic criteria for LATE, aiming both to stimulate research and to promote awareness of this pathway to dementia. We report consensus-based recommendations including guidelines for diagnosis and staging of LATE-NC. For routine autopsy workup of LATE-NC, an anatomically-based preliminary staging scheme is proposed with TDP-43 immunohistochemistry on tissue from three brain areas, reflecting a hierarchical pattern of brain involvement: amygdala, hippocampus, and middle frontal gyrus. LATE-NC appears to affect the medial temporal lobe structures preferentially, but other areas also are impacted. Neuroimaging studies demonstrated that subjects with LATE-NC also had atrophy in the medial temporal lobes, frontal cortex, and other brain regions. Genetic studies have thus far indicated five genes with risk alleles for LATE-NC: GRN, TMEM106B, ABCC9, KCNMB2, and APOE. The discovery of these genetic risk variants indicate that LATE shares pathogenetic mechanisms with both frontotemporal lobar degeneration and Alzheimer's disease, but also suggests disease-specific underlying mechanisms. Large gaps remain in our understanding of LATE. For advances in prevention, diagnosis, and treatment, there is an urgent need for research focused on LATE, including in vitro and animal models. An obstacle to clinical progress is lack of diagnostic tools, such as biofluid or neuroimaging biomarkers, for ante-mortem detection of LATE. Development of a disease biomarker would augment observational studies seeking to further define the risk factors, natural history, and clinical features of LATE, as well as eventual subject recruitment for targeted therapies in clinical trials.

  • 3. Nichols, Emma
    et al.
    Szoeke, Cassandra E. I.
    Vollset, Stein Emil
    Abbasi, Nooshin
    Abd-Allah, Foad
    Abdela, Jemal
    Aichour, Miloud Taki Eddine
    Akinyemi, Rufus O.
    Alahdab, Fares
    Asgedom, Solomon W.
    Awasthi, Ashish
    Barker-Collo, Suzanne L.
    Baune, Bernhard T.
    Bejot, Yannick
    Belachew, Abate B.
    Bennett, Derrick A.
    Bijani, Belete Biadgo Ali
    Bin Sayeed, Muhammad Shahdaat
    Brayne, Carol
    Carpenter, David O.
    Carvalho, Felix
    Catala-Lopez, Ferran
    Cerin, Ester
    Choi, Jee-Young J.
    Dang, Ahn K.
    Degefa, Meaza G.
    Djalalinia, Shirin
    Dubey, Manisha
    Duken, Eyasu Ejeta
    Edvardsson, David
    Umeå University, Faculty of Medicine, Department of Nursing. School of Nursing and Midwifery, La Trobe University, Melbourne, VIC, Australia.
    Endres, Matthias
    Eskandarieh, Sharareh
    Faro, Andre
    Farzadfar, Farshad
    Fereshtehnejad, Seyed-Mohammad
    Fernandes, Eduarda
    Filip, Irina
    Fischer, Florian
    Gebre, Abadi K.
    Geremew, Demeke
    Ghasemi-Kasman, Maryam
    Gnedovskaya, Elena V.
    Gupta, Rajeev
    Hachinski, Vladimir
    Hagos, Tekleberhan B.
    Hamidi, Samer
    Hankey, Graeme J.
    Haro, Josep M.
    Hay, Simon I.
    Irvani, Seyed Sina N.
    Jha, Ravi P.
    Jonas, Jost B.
    Kalani, Rizwan
    Karch, Andre
    Kasaeian, Amir
    Khader, Yousef Saleh
    Khalil, Ibrahim A.
    Khan, Ejaz Ahmad
    Khanna, Tripti
    Khoja, Tawfik A. M.
    Khubchandani, Jagdish
    Kisa, Adnan
    Kissimova-Skarbek, Katarzyna
    Kivimaki, Mika
    Koyanagi, Ai
    Krohn, Kristopher J.
    Logroscino, Giancarlo
    Lorkowski, Stefan
    Majdan, Marek
    Malekzadeh, Reza
    Marz, Winfried
    Massano, Joao
    Mengistu, Getnet
    Meretoja, Atte
    Mohammadi, Moslem
    Mohammadi-Khanaposhtani, Maryam
    Mokdad, Ali H.
    Mondello, Stefania
    Moradi, Ghobad
    Nagel, Gabriele
    Naghavi, Mohsen
    Naik, Gurudatta
    Nguyen, Long H.
    Nguyen, Trang H.
    Nirayo, Yirga L.
    Nixon, Molly R.
    Ofori-Asenso, Richard
    Ogbo, Felix A.
    Olagunju, Andrew T.
    Owolabi, Mayowa O.
    Panda-Jonas, Songhomitra
    Passos, Valeria M. de Azeredo
    Pereira, David M.
    Pinilla-Monsalve, Gabriel D.
    Piradov, Michael A.
    Pond, Constance D.
    Poustchi, Hossein
    Qorbani, Mostafa
    Radfar, Amir
    Reiner, Robert C.
    Robinson, Stephen R.
    Roshandel, Gholamreza
    Rostami, Ali
    Russ, Tom C.
    Sachdev, Perminder S.
    Safari, Hosein
    Safiri, Saeid
    Sahathevan, Ramesh
    Salimi, Yahya
    Satpathy, Maheswar
    Sawhney, Monika
    Saylan, Mete
    Sepanlou, Sadaf G.
    Shafieesabet, Azadeh
    Shaikh, Masood A.
    Sahraian, Mohammad A.
    Shigematsu, Mika
    Shiri, Rahman
    Shiue, Ivy
    Silva, Joao P.
    Smith, Mari
    Sobhani, Soheila
    Stein, Dan J.
    Tabares-Seisdedos, Rafael
    Tovani-Palone, Marcos R.
    Tran, Bach X.
    Tran, Tung T.
    Tsegay, Amanuel T.
    Ullah, Irfan
    Venketasubramanian, Narayanaswamy
    Vlassov, Vasily
    Wang, Yuan-Pang
    Weiss, Jordan
    Westerman, Ronny
    Wijeratne, Tissa
    Wyper, Grant M. A.
    Yano, Yuichiro
    Yimer, Ebrahim M.
    Yonemoto, Naohiro
    Yousefifard, Mahmoud
    Zaidi, Zoubida
    Zare, Zohreh
    Feigin, Valery L.
    Vos, Theo
    Murray, Christopher J. L.
    Global, regional, and national burden of Alzheimer's disease and other dementias, 1990-2016: a systematic analysis for the Global Burden of Disease Study 20162019In: Lancet Neurology, ISSN 1474-4422, E-ISSN 1474-4465, Vol. 18, no 1, p. 88-106Article in journal (Refereed)
    Abstract [en]

    Background: The number of individuals living with dementia is increasing, negatively affecting families, communities, and health-care systems around the world. A successful response to these challenges requires an accurate understanding of the dementia disease burden. We aimed to present the first detailed analysis of the global prevalence, mortality, and overall burden of dementia as captured by the Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study 2016, and highlight the most important messages for clinicians and neurologists.

    Methods: GBD 2016 obtained data on dementia from vital registration systems, published scientific literature and surveys, and data from health-service encounters on deaths, excess mortality, prevalence, and incidence from 195 countries and territories from 1990 to 2016, through systematic review and additional data-seeking efforts. To correct for differences in cause of death coding across time and locations, we modelled mortality due to dementia using prevalence data and estimates of excess mortality derived from countries that were most likely to code deaths to dementia relative to prevalence. Data were analysed by standardised methods to estimate deaths, prevalence, years of life lost (YLLs), years of life lived with disability (YLDs), and disability-adjusted life-years (DALYs; computed as the sum of YLLs and YLDs), and the fractions of these metrics that were attributable to four risk factors that met GBD criteria for assessment (high body-mass index [BMI], high fasting plasma glucose, smoking, and a diet high in sugarsweetened beverages).

    Findings: In 2016, the global number of individuals who lived with dementia was 43.8 million (95% uncertainty interval [UI] 3 7. 8-51.0), increased from 20.2 million (17. 4-23 5) in 1990. This increase of 117% (95% UI 114-121) contrasted with a minor increase in age-standardised prevalence of 1.7% (1.0-2.4), from 701 cases (95% UI 602-815) per 100 000 population in 1990 to 712 cases (614-828) per 100 000 population in 2016. More women than men had dementia in 2016 (27.0 million, 95% UI 23 .3-31. 4, vs 16.8 million, 14.4-19.6), and dementia was the fifth leading cause of death globally, accounting for 2.4 million (95% UI 2.1-2.8) deaths. Overall, 28.8 million (95% UI 24. 5-34. 0) DALYs were attributed to dementia; 6.4 million (95% UI 3 .4-10. 5) of these could be attributed to the modifiable GBD risk factors of high BMI, high fasting plasma glucose, smoking, and a high intake of sugar-sweetened beverages.

    Interpretation: The global number of people living with dementia more than doubled from 1990 to 2016, mainly due to increases in population ageing and growth. Although differences in coding for causes of death and the heterogeneity in case-ascertainment methods constitute major challenges to the estimation of the burden of dementia, future analyses should improve on the methods for the correction of these biases. Until breakthroughs are made in prevention or curative treatment, dementia will constitute an increasing challenge to health-care systems worldwide.

  • 4. Riso, Lukas
    et al.
    Kaaks, Rudolf
    Kuehn, Tilman
    Sookthai, Disorn
    Forsgren, Lars
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Trupp, Miles
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Trichopoulou, Antonia
    La Vecchia, Carlo
    Karakatsani, Anna
    Gavrila, Diana
    Ferrari, Pietro
    Freisling, Heinz
    Petersson, Jesper
    Lewan, Susanne
    Vemeulen, Roel Ch.
    Panico, Salvatore
    Masala, Giovanna
    Ardanaz, Eva
    Krogh, Vittorio
    Perneczky, Robert
    Middleton, Lefkos T.
    Mokoroa, Olatz
    Sacerdote, Carlotta
    Sieri, Sabrina
    Hayat, Shabina A.
    Brayne, Carol
    Riboli, Elio
    Vineis, Paolo
    Gallo, Valentina
    Katzke, Verena A.
    General and abdominal adiposity and the risk of Parkinson's disease: A prospective cohort study2019In: Parkinsonism & Related Disorders, ISSN 1353-8020, E-ISSN 1873-5126, Vol. 62, p. 98-104Article in journal (Refereed)
    Abstract [en]

    Introduction: Due to demographic change, an increase in the frequency of Parkinson's disease (PD) patients is expected in the future and, thus, the identification of modifiable risk factors is urgently needed. We aimed to examine the associations of body mass index (BMI) and waist circumference (WC) with incident PD. Methods: In 13 of the 23 centers of the European Prospective Investigation into Cancer and Nutrition (EPIC) study, a total of 734 incident cases of PD were identified between 1992 and 2012 with a mean follow-up of 12 years. Cox proportional hazards regression was used to calculate hazard ratios (HR) with 95% confidence intervals (CI). We modelled anthropometric variables as continuous and categorical exposures and performed subgroup analyses by potential effect modifiers including sex and smoking. Results: We found no association between BMI, WC and incident PD, neither among men nor among women. Among never and former smokers, BMI and waist circumference were also not associated with PD risk. For male smokers, however, we observed a statistically significant inverse association between BMI and PD risk (HR 0.51, 95%CI: 0.30, 0.84) and the opposite for women, i.e. a significant direct association of BMI (HR 1.79, 95%CI: 1.04, 3.08) and waist circumference (HR 1.64, 95%CI: 1.03, 2.61) with risk of PD. Conclusion: Our data revealed no association between excess weight and PD risk but a possible interaction between anthropometry, sex and smoking.

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