{"id":288386,"date":"2019-06-18T16:46:22","date_gmt":"2019-06-18T19:46:22","guid":{"rendered":"http:\/\/revistapesquisa.fapesp.br\/?p=288386"},"modified":"2019-06-24T16:18:10","modified_gmt":"2019-06-24T19:18:10","slug":"before-memory-loss","status":"publish","type":"post","link":"https:\/\/revistapesquisa.fapesp.br\/en\/before-memory-loss\/","title":{"rendered":"Before memory loss"},"content":{"rendered":"

Difficulty finding the car keys, absentmindedly placed in the sock drawer instead of the usual key holder, or the terrifying inability to remember the way home after going for a run through the neighborhood, as experienced by the university professor in the 2014 movie Still Alice<\/em>, may not be the first signs of Alzheimer\u2019s. The illness, which was identified slightly more than a century ago by German psychiatrist and neuroanatomist Alois Alzheimer, and almost simultaneously, by Czech psychiatrist and neuroanatomist Oskar Fischer, gradually destroys brain cells and is known for erasing memory and reducing the ability to plan and carry out daily tasks, such as writing a grocery list. These signs, however, are typical of the advanced stages of the disease. Much earlier, it can manifest in a more disguised manner, being confused with more common societal problems, such as depression, anxiety, or abrupt changes in sleep patterns or appetite.<\/p>\n

For some time, it has been known that these psychiatric disturbances are more frequent among people who develop Alzheimer\u2019s as they age, than among the healthy senior population. Based on population studies, some neurologists and mental health experts argue that depression and anxiety appear first, caused by isolation and other difficulties faced with aging, and, if left untreated, increase the risk of Alzheimer\u2019s. Evidence is beginning to appear that, at least in some cases, the opposite may occur: psychiatric events result from neurological lesions in the initial stages of Alzheimer\u2019s.<\/p>\n

There are solid indications from the work of Brazilian neuropathologist Lea Tenenholz Grinberg that psychiatric problems precede memory loss and dementia, which arise two to three decades after the first neurological damage of Alzheimer\u2019s. Tenenholz Grinberg, a professor at the University of S\u00e3o Paulo (USP) and the University of California in San Francisco (UCSF) in the United States, along with her Brazilian and North American colleagues, observed that, after the first lesions appear, the risk of psychiatric problems increases. The probability of developing anxiety and changes (increase or decrease) in appetite and sleep is three times greater for those with the initial lesions than for those without. Furthermore, the risk of depression and of restlessness are four times and six times greater, respectively. \u201cThese results indicate that, in some cases, Alzheimer\u2019s already exists in areas that modulate cerebral activity when the first psychiatric events appear,\u201d confirms Tenenholz Grinberg.<\/p>\n

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L\u00e9o Ramos Chaves <\/span><\/a> Specimens of brain tissue stored at the Biobanco for the Study of Aging at USPL\u00e9o Ramos Chaves <\/span><\/p><\/div>\n

Researchers arrived at this conclusion after analyzing the brains of 455 people between the ages of 58 and 82. The brain specimens had been stored in the Biobanco for the Study of Aging at USP, one of the largest brain collections in the world. This collection holds 3,000 specimens that have been donated by the families of individuals who have been autopsied by the Capital\u2019s Death Verification Service in S\u00e3o Paulo. In the study, the authors did not only analyze the brain. They also inspected the brainstem, which together with the cerebellum and the brain, comprise the encephalon, a group of structures housed in the brain. In 2009, Tenenholz Grinberg and the teams of the German neuroanatomist Helmut Heinsen, at the time with the University of W\u00fcrzburg in Germany, and of neurologist Ricardo Nitrini, and of geriatric physician Wilson Jacob Filho, both from USP, confirmed that one of the first structures damaged by Alzheimer\u2019s was the brainstem, and not the brain (see<\/em> Pesquisa FAPESP issue no. 153<\/em><\/a>).<\/p>\n

More recently, in an article published in October of this year in the Journal of Alzheimer\u2019s Disease<\/em>, the researchers grouped the cases according to the classification proposed by the German neuroanatomists Heiko Braak and Eva Braak (1939\u20132000). Presented in 1991, the scale organizes cases of Alzheimer\u2019s in six stages, which increase in severity as the number of lesions grows as well as the affected areas of the encephalon. The scale was revised in 2011 by Heiko Braak in order to incorporate evidence that the first regions to be affected by Alzheimer\u2019s are in the brainstem.<\/p>\n

Indications that psychiatric disturbances occur prior to memory loss were proven when the teams from USP and UCSF compared the evolution of brain damage observed under microscope with the psychiatric problems and clinical signs of Alzheimer\u2019s exhibited by patients months before dying. Even in stages 1 and 2, when there are few lesions and they are concentrated in the structures of the brainstem, such as the dorsal raphe nucleus and the locus coeruleus<\/em>, signs of depression, anxiety, restlessness, and changes in appetite and sleep were more frequent.<\/p>\n<\/div><\/a>