Context: Beta-site alpha-amyloid protein cleaving enzyme1 (BACE1) plays a key role in the pathogenesis of Alzheimer’s disease. Additional to its moderate expression in the brain, high levels of BACE1 mRNA were found in the pancreas. Murine Bace1 has been immunohistochemicaly detected at the apical pole of acinar cells within the exocrine pancreas of mice and Bace1 activity was observed in pancreatic juice. In vitro experiments revealed enteropeptidase as a putative substrate for Bace1 suggesting a role in acute pancreatitis.

Dysfagi, sväljningssvårigheter, är en vanlig komplikation vid Alzheimers sjukdom och är väl utforskat i det sista av de tre stadierna vid demens (lindrig, måttlig och svår). Sväljningssvårigheter som har kopplats samman med Alzheimers sjukdom är ett förändrat ätbeteende, reducerad höjning av larynx och en längre oral fas. Syftet med studien var att undersöka om och vilka symtom vid dysfagi som kan ses i de tidigare stadierna av Alzheimers sjukdom vid användning av icke-invasiva undersökningsmetoder. En enkätundersökning med 16 deltagare och en sväljningsscreening med fyra deltagare genomfördes. Sväljningsscreeningen bestod av fyra delar: oralmotorik, sväljningstest och sväljningskapacitetstest med vatten och tuggfunktion. Resultaten från enkäten visade ingen högre andel med sväljningssvårigheter i den testade gruppen jämfört med tidigare forskning av normalpopulationen. Inga signifikanta samband mellan olika parametrar såsom poäng på Mini Mental Test (MMT), tid för diagnos och poäng på enkäten hittades. Resultaten från sväljningsscreeningen visade en tendens till förlängd orofaryngeal fas vid ett sväljningskapacitetstest vilket indikerar att undersökning av sväljningskapacitet kan vara en användbar metod för att identifiera tidiga sväljningssvårigheter vid Alzheimers sjukdom. Testet är lätt att genomföra och inte tidskrävande. / Dysphagia, eating disorders, is a common complication associated with Alzheimer’s disease and has been studied extensively in the three late stages of dementia (mild, moderate and severe). Eating disorders that have been linked to Alzheimer’s disease are a changed eating behaviour, reduced laryngeal elevation and a prolonged oral phase. The purpose of this study was to investigate if and which symptoms of dysphagia can be identified using non-invasive methods. A survey with 16 participants and a swallowing screening with four participants were conducted. The swallowing screening consisted of four parts: oral motor abilities, a swallowing test and a swallowing capacity test with water and chewing function. The results from the survey did not show an increased prevalence of eating disorders in the test group compared to what previous research suggests could be expected for the normal population. No significant correlations between parameters such as Mini Mental Test (MMT), time elapsed since diagnosis or score of the survey were found. The results from the swallowing screening showed a tendency towards a prolonged oropharyngeal phase in a swallowing capacity test, indicating that examination of swallowing capacity could be a useful method for identifying early eating disorders in Alzheimers disease. The test is easy to perform and is not time consuming.

<p>Alzheimers sjukdom påverkar både patienten och den som vårdar honom eller henne. En anhörig vårdar ofta patienten och det har visat sig att de är utsatta för olika svårigheter.  Syftet med denna studie var att beskriva anhörigas upplevelser av att vårda en familjemed­lem med Alzheimers sjukdom. Metoden som användes för att besvara syftet var att göra en litteraturstudie enligt Polit och Becks (2004) beskrivning av genomförandet av en litteratur­studie. Dataanalysen skedde med kvalitativ ansats genom att artiklarna lästes igenom nog­grant och gemensamheter och mönster bland anhörigvårdares upplevelser söktes. Studiens resultat baserades på åtta veten­skapliga artiklar från vilka fem teman framkom. Resultatet visade att många anhörigvår­dare upplevde en förlust av relationer. De saknade relationen både med patienten och med vänner. De tyckte även att det var viktigt att ha fritid och tid för sig själva, vilket ofta var svårt att åstadkomma. Viljan till att söka ny kunskap blev stor när de tog på sig rollen som anhörigvårdare, och många upplevde olika lidanden och besvär såsom skuld och de­pression. Upplevelserna i resultatet åskådliggjorde att en stor del av de anhöriga inte kände välbefinnande. Detta resultat pekar på vikten av att sjuksköterskor är medvetna om de upplevelser och känslor anhörigvårdare har.</p> / <p>Alzheimer’s disease afflicts both the patient and the person caring for him or her. A relative often provides care for the patient and it appears as though they are exposed to different adversities. The aim of this study was to describe the experiences of relatives which care for a family member suffering from Alzheimer’s disease. The method used to answer the aim was to do a literature review by using Polit and Becks (2004) description of how to make a literature review. The data analysis was made with a qualitative approach by reading the articles accurately and patterns among the experiences family caregivers have been sought. The results of the study are based on eight scientific articles. Five themes emerged from these articles. The results show that many family caregivers experienced a loss of relationships. They missed the relationship with the patient as well as the relationship with friends. They also thought that it was important to have leisure, which often is hard to accomplish. The desire to seek for new knowledge became large when they became family caregivers, and many of them experienced different sufferings and troubles such as guilt and depression. The results show that many of the relatives did not experience well-being. On account of this it is important that nurses know about the experiences and feelings family caregivers have.</p>

Alzheimer’s disease (AD) is the most common neurodegenerative disease affecting the elderly population and is believed to be caused by the overproduction and accumulation of the toxic amyloid beta (Aβ) peptide in the brain. Aβ is produced by two separate enzymatic cleavage events of the larger membrane bound amyloid precursor protein, APP. The first, and rate-limiting, cleavage event is made by beta-secretase, or BACE1, and is thus an attractive therapeutic target. Our lab, as well as many others, has shown that BACE1 protein and activity are increased in late-stage sporadic AD. We have extended these findings to show that BACE1 is increased in the earliest stages of AD before the onset of significant Aβ accumulation, indicating a potential causal role in the disease. Interestingly, BACE1 mRNA levels are unchanged in AD, leading to reason that a post-transcriptional method of BACE1 regulation is altered in disease. To date, the mechanism for this aberrant post-transcriptional regulation has not been elucidated. This study has implicated the cellular nucleic acid binding protein (CNBP), a highly conserved RNA binding protein, as a positive regulator of BACE1 translation, with implications for the etiology of sporadic AD. CNBP overexpression in cultured cells or spiked into a cell-free in vitro translation system increased BACE1 protein expression without affecting BACE1 mRNA levels. Knockdown of CNBP reduced BACE1 protein and mRNA slightly. Furthermore, CNBP associated with BACE1 mRNA in cell lysates and bound directly to the BACE1 5’ UTR in vitro, which confers most of the regulatory activity. Importantly, CNBP was increased in the progression of AD and correlated with BACE1 expression. Cellular stressors (such as glucose deprivation and oxidative stress) that occur in the AD brain increase BACE1 translation and we have found that these stressors increased CNBP expression as well. Early experimental evidence suggests that CNBP may enhance BACE1 translation through a cap-independent mechanism, which is an alternative translational pathway activated by cell stress. These studies indicate that the RNA binding protein CNBP is a novel trans-acting factor important for the regulation of BACE1 protein production and may be a viable therapeutic target for AD.

Background Dementia is a national priority for Scotland, and as such, fast and accurate diagnosis plus responsive and well-evidenced interventions post-diagnosis are key. Accurately estimating an individual’s level of premorbid functioning can be a crucial part of establishing that cognitive decline has taken place, enabling clinicians to be more confident and accurate in their diagnosis. Measures that assess premorbid ability should be able to 1) capture current ability in healthy controls and 2) resist the effects of cognitive decline when used in individuals with dementia. At the post-diagnostic stage, there is a growing evidence base for non-pharmacological, tailored interventions for individuals with dementia. However, the evidence base is limited, particularly so for Cognitive Rehabilitation. Objectives An empirical study was conducted in order to assess whether a newly developed measure that aims to capture lifelong cognitive reserve (the brain’s ability to withstand pathological change), the Cognitive Reserve Index Questionnaire (CRIq), can capture premorbid ability. Three research questions were addressed; 1) does the CRIq capture current ability in healthy controls? 2) is it resistant to cognitive decline when used with a patient group with dementia? and 3) how does the CRIq compare to a traditional measure of premorbid ability, the NART (National Adult Reading Test)? Another focus of development and innovation in dementia research is that of post-diagnostic interventions. A systematic review was therefore conducted in order to evaluate the effectiveness of Cognitive Rehabilitation for mild-moderate dementia (Alzheimer disease or mixed dementia) in relation to cognitive and functional outcomes. Due to the limited number of RCTs in this field precluding a clear understanding of the evidence base, the additional contribution of non-RCTs was also evaluated. Method For the empirical study N=20 healthy older controls and N=13 patients with dementia were recruited. In order to appropriately address the three research questions both groups were assessed using the NART, the CRIq and the MOCA (Montreal Cognitive Assessment). In addition, the control group were assessed on a measure of current ability, the WAIS-IV Perceptual Reasoning Index. For the systematic review of Cognitive Rehabilitation the CDCIG Specialised Register, ALOIS, was searched in order to identify relevant studies. In addition, previous reviews were searched to identify studies excluded on the basis that they were not an RCT. Results Results for the empirical study show both CRIq and NART were strongly correlated to current ability (performance on WAIS-IV PRI) in controls, although both significantly overestimated ability. CRIq performance was not affected by the presence of dementia whereas NART predicted premorbid ability was. CRIq and NART showed a different pattern of results between controls and patients, indicating that CRIq may more resistant to the effects of cognitive decline. Ten studies were identified for the systematic review; five RCT and five non-RCT. Study quality was assessed using a well-validated quality assessment tool, and indicated large variability. Eight of the ten studies reported a positive effect of Cognitive Rehabilitation. However, several studies were of poor quality and included aspects of other approaches in their intervention (e.g. Cognitive Training, Cognitive-Behaviour Therapy). Conclusions The empirical study found that CRIq over-estimated current ability in controls, but was resistant to cognitive decline in patients. The over-estimation of current ability may be accounted for by the CRIq being normed on an Italian population, thus not reflecting UK cultural norms (e.g. for length of schooling). When the NART and the CRIq were directly compared, the two measures were found to be related, but yet produced significantly different estimates of premorbid ability. This suggests that they may capture different facets of premorbid functioning, with the NART being primarily a verbal performance-based measure, and the CRIq capturing aspects of global cognitive functioning. Clinical implications include the potential utility of the CRIq for patients with language impairment. However the study conclusions are limited by a low N, and therefore have restricted generalisability. In the systematic review, the literature was exhaustively searched and evidence was found for the effectiveness of Cognitive Rehabilitation for mild-moderate Alzheimer disease and mixed dementia. Methodological limitations of the included studies are discussed, and clinical implications are identified. Both the empirical study and the systematic review highlight the need for greater research and development of methods by which dementia care is supported; through more effective methods of diagnosis, to a better evidence base for post-diagnostic interventions.

Background: Unawareness of memory functioning is a key symptom of Alzheimer’s disease and dementia that has been demonstrated to be related to a number of important factors for the person with dementia (PwD) and their family caregivers including quality of life and depression. Understanding more about how awareness relates to these factors will help inform how PwD and their caregivers are best supported. Objective: A meta-analysis was conducted in order to examine the relationship between Awareness and depression in dementia. An empirical study was conducted to examine the contribution awareness provides to explaining PWDs’ Quality of Life (QoL). PwD have been found to be aware of factors that affect their caregiver and so caregiver wellbeing and quality of life and the quality of the caregiving relationship were also investigated as well as more established predictors of quality of life for PwD. Both PwD self-ratings and caregiver ratings of the PwD they care for of QoL were examined as they have been shown to be affected by different factors. Method: Meta-analysis: A search of electronic databases Psycinfo, Embase and Medline was conducted. A meta-analysis of correlations was undertaken examining the relationship between awareness and depression in dementia. Empirical study: 27 PwD and their caregivers were recruited. In order to assess the research aims the PwD completed measures of: Quality of life (Quality Of Life-Alzheimer’s Disease scale), awareness of memory functioning (Memory Awareness Rating Scale-Adjusted), cognitive functioning (Addenbrooke’s Cognitive Exam-R), depression and anxiety (Hospital Anxiety and Depression Scale). The caregiver completed measures of: PwD Quality of life (Quality Of Life-Alzheimer’s Disease scale proxy), Memory Functioning Scale (from MARSA), self-ratings of depression and anxiety (Hospital Anxiety and Depression Scale), activities of daily living (Disability Assessment in Dementia), Neuropsychiatric symptoms (Neuropsychiatric symptoms inventory-Questionnaire), caregiver burden (Zarit Burden Inventory), and rating of relationship quality with PwD (Burns Relationship Satisfaction Scale). Results: Meta-analysis: Thirty-one studies were identified. A small association was found between awareness and depression with substantial amount of heterogeneity (- 0.23). Analysing the studies that excluded major depression demonstrated that mild depression had a moderate negative relationship with awareness (-0.42). Subgroup analysis showed that the different measures of awareness used seemed to suggest different effects with depression for different measures. Empirical study: Awareness was not found to predict PwD rated or caregiver rated QoL. No caregiver variables predicted PwD QoL. Depression and neuropsychiatric symptoms predicted PwD QoL. Caregiver rated QoL was predicted by activities of daily living and caregiver rated quality of caregiving relationship. Conclusions: Meta-analysis: The effect between mild depression and lack of awareness but not major depression supports the assertion that unawareness is a psychological response to decline in memory functioning in dementia. Neither depression nor awareness appear to be unitary constructs in PwD. Empirical study: Awareness not related to PwD QoL. The quality of caregiving relationship is important to QoL in a dementia context. PwD and their caregivers rate the QoL of PwD differently.

Bakgrund: Enligt WHO drabbas ungefär tio miljoner människor av demens varje år varav 60 till 70 procent av Alzheimers sjukdom. I Sverige är upp emot var femte vuxen en regelbunden informell vårdgivare till någon i sin omgivning. Informell vård innebär den omsorg som närstående ger till vårdtagaren. Behovet av närståendes närhet ökar ofta under insjuknandet i Alzheimers sjukdom. Sjuksköterskan har en hälsofrämjande och sjukdomsförebyggande funktion och har en roll som rådgivare där denne vägleder vårdtagare och deras närstående. Syfte: Syftet var att belysa närståendes upplevelser kring vårdandet av familjemedlemmar med Alzheimers sjukdom. Metod: En litteraturöversikt genomfördes där tio artiklar med kvalitativ design granskades och analyserades enligt Friberg. Dessa artiklar framkom ur databaserna Cinahl Complete, Pubmed, Medline och PsykINFO. Sökord som användes var ”Alzheimers disease”, ”experience”, ”relatives” och ”family”. Resultat: Fyra huvudteman konstruerades. Transitionen från närstående till att bli vårdgivare, här framkom det att närstående upplevde maktlöshet, tvivel och en förlust av autonomi. Älta det förflutna och känna oro för framtiden, närstående upplevde en känsla av oro inför framtiden både för vårdtagaren och dem själva. Upplevelsen av stigmatisering och isolering, närstående upplevde att de blev isolerade och kände av en stigmatisering i samhället. Att förlora samhörigheten och stärka den, närstående belyste att relationen med vårdtagaren förändrades till följd av sjukdomens inverkan.  Diskussion: Resultatet diskuterades utifrån Callista Roys teori om adaption. Diskussionen fördes kring hur upplevelserna hos närstående kan förstås utifrån denna teori och det som framkom i resultatet. Närstående genomgår en övergång till att bli en vårdgivare och befinner sig i en föränderlig miljö där adaption eftersträvas för att finna en balans i livet. En diskussion fördes kring sjuksköterskans roll i samspelet med närstående. / Background: According to WHO, approximately ten million people are affected by dementia each year, of which 60 to 70 percent are suffering from Alzheimer's disease. In Sweden, every fifth adult is an informal caregiver to someone in their environment. Informal care involves the care that relatives give to their care recipient. At the onset of Alzheimer's disease, the need of closeness to the relatives often increases. The nurse has a health promoting and disease preventing function and has a role as an adviser in which he/she guides the care recipient and their relatives. Aim: The aim was to illustrate the experiences of relatives in caring for family members with Alzheimer´s Disease.  Method: A literature review was conducted where ten articles of qualitative design were examined and analyzed according to Friberg. These articles came from the databases Cinahl Complete, Pubmed, Medline and PsychInFO. Keywords used were "Alzheimers Disease", "Experience," "Relatives," and "Family." Results: Four main themes were constructed. The transition from relative to becoming a caregiver, here it emerged that relatives experienced powerlessness, doubt and a loss of autonomy. Dwelling on the past and Feeling worried about the future, relatives experienced a sense of concern for the future both for the care recipient and for themselves. The experience of stigmatization and isolation, relatives felt that they were isolated and felt stigma in society. The loss of togetherness and strengthen it, relatives explained that the relationship with the care recipient changed as a result of the effect of the disease.  Discussion: The results was discussed based on Callista Roys theory of adaptation. The discussion was conducted in relation to how the experiences of relatives can be understood based on this theory, and other findings that emerged from the results. Relatives undergo a transition to becoming a caregiver and are in a changing environment where adaptation is sought to find a balance in life. A discussion was held about the nurse's role in the interaction with relatives.

A doença de Alzheimer é uma doença neurodegenerativa que causa perdas de memória, danos cognitivos e no comportamento, sendo considerada uma das causas principais de demência entre a população. Esta doença é caracterizada por uma intensa perda neuronal colinérgica, de forma que tanto os inibidores da enzima acetilcolinesterase (AChE) quanto compostos antioxidantes possam ser empregados como neuroprotetores. Nesse sentido, plantas da família Lycopodiaceae vêm sendo estudadas como fonte de novos alcalóides anticolinesterásicos desde a descoberta da huperzina A, isolada a partir da planta chinesa Huperzia serrata. Este trabalho foi realizado com o objetivo de caracterizar e isolar os alcalóides majoritários de Huperzia acerosa, H. heterocarpon, H. quadrifariata, H. reflexa, Lycopodiella cernua, Lycopodium clavatum e L. thyoides, de ocorrência no estado do Rio Grande do Sul, bem como avaliar as atividades anticolinesterásicas e antioxidantes in vitro e in vivo para os extratos. Extratos de alcalóides totais de espécies de L. clavatum e L. thyoides ocorrentes no Brasil e Argentina foram comparados quanto ao seu conteúdo químico, aliado à atividade anticolinesterásica. A atividade inibitória para AChE e butirilcolinesterase (BuChE) dos alcalóides isolados também foi ensaiada, juntamente com a determinação das propriedades citotóxicas exercidas pelos extratos sobre uma linhagem de gliomas C6. Todos os extratos de alcalóides foram analisados através de CG-EM, sendo os perfis de fragmentação dos compostos comparados através de dados da literatura. L. clavatum e L. thyoides possuem perfil químico similar, com licopodina e acetildiidrolicopodina como alcalóides principais, enquanto que L. cernua possui apenas dois alcalóides, cernuína e licocernuína. Os extratos de alcalóides de H. acerosa, H. quadrifariata e H. reflexa também foram analisados, sendo detectados tanto compostos do grupo licopodano quanto do grupo flabelidano, juntamente com outros alcalóides cujas estruturas ainda são desconhecidas. Os alcalóides encontrados em H. heterocarpon não puderam ser elucidados a partir de dados de fragmentação, uma vez que eles não coincidiram com nenhum perfil da literatura. Nesse estudo verificamos que dentre os extratos analisados, H. quadrifariata e H. reflexa promoveram a maior inibição para a enzima AChE obtida de eritrócitos humanos, com IC50 de 2,0 e 0,11 μg/mL, respectivamente, enquanto que H. heterocarpon foi o único extrato com maior seletividade para a BuChE (IC50 = 8,3 μg/mL). Além disso, dentre os alcalóides isolados licopodina, acetildiidrolicopodina, cernuína, licocernuína e clavolonina, apenas acetildiidrolicopodina e cernuína possuem inibição importante, sendo que nenhum deles possui efeito butirilcolinesterásico significativo. Também foi estimada a atividade anticolinesterásica para os extratos de alcalóides totais de L. clavatum e L. thyoides empregando-se homogenatos de córtex, hipocampo e estriato de ratos como fonte enzimática, sendo determinadas suas curvas de inibição com distintos tempos de incubação em uma faixa de concentrações. Também foi verificada para os dois extratos uma inibição do tipo competitiva/não-competitiva, bem como seu perfil antioxidante in vitro pelos métodos de descoloração do radical DPPH, degradação da 2-deoxirribose, TRAP e óxido nítrico. Após um tratamento agudo em camundongos de 14 meses com os extratos, foram verificados os efeitos antioxidantes através do método de TBA-RS, e para as enzimas catalase e superóxido dismutase. Do mesmo modo, verificamos que os mesmos extratos promoveram uma diminuição na atividade da acetilcolinesterase, quando administrados por via intraperitoneal. Nessa metodologia, os extratos mais potentes foram H. quadrifariata e H. reflexa, corroborando o efeito in vitro encontrado para os mesmos. Os extratos purificados de alcalóides de L. clavatum e L. thyoides com habitat no Brasil e Argentina foram comparados quanto ao seu perfil químico e biológico. Nesse estudo, foi verificado que os alcalóides licopodina e acetildiidrolicopodina são os compostos majoritários para todas as espécies, tendo L. clavatum maior atividade anticolinesterásica em relação a L. thyoides, tanto a espécie brasileira quanto a espécie argentina. / Alzheimer’s disease is a neurodegenerative disease which causes memory loss, cognitive and behavioral damages, considered to be the leading cause of dementia among the elderly. This disease is characterized for an intense cholinergic loss, and the use of acetylcholinesterase (AChE) inhibitors together with antioxidant compounds as neurprotectors is a strategy for the treatment. In this sense, Lycopodiaceae plants are well studied as a source of new anticholinesterasic alkaloids since the discovery of huperzine A, isolated from Chinese Huperzia serrata. This work was conducted with the objective of characterize and isolate the main alkaloids from Huperzia acerosa, H. heterocarpon, H. quadrifariata, H. reflexa, Lycopodiella cernua, Lycopodium clavatum and L. thyoides, with occurrence in Rio Grande do Sul state, and also evaluate the anticholinesterasic and antioxidant activities in vitro and in vivo for the extracts. Alkaloidal extracts from L. clavatum and L. thyoides species with habitat in Brazil and Argentina were compared to their chemical content, together with their anticholinesterasic activity. The inhibitory effect for AChE and butyrylcholinesterase (BuChE) for the isolated alkaloids was also evaluated, together with the determination of the cytotoxic properties exherced by the extracts in a gliome C6 cell line. Every alkaloidal extract was analyzed by means of GC-MS, and the fragmentation patterns for the compounds were compared with those from literature. L. clavatum and L. thyoides have similar chemical profile, with lycopodine and acetyldihydrolycopodine as main alkaloids, while L. cernua has only two alkaloids, cernuine and lycocernuine. The alkaloidal extracts of H. acerosa, H. quadrifariata e H. reflexa were also analyzed, and compounds from lycopodane and flabellidane groups were detected, along with other alkaloids whose structures are still unknown. The alkaloids found in H. heterocarpon could not be elucidated with fragmentation dates so far, since they did not coincide with those found in literature. We also verified that among the extracts, H. quadrifariata and H. reflexa promoted a higher inhibition for AChE obtained from human erythrocytes, with a IC50 value of 2,0 e 0,11 μg/mL, respectively, while H. heterocarpon extract was the only more selective for BuChE (IC50 = 8,3 μg/mL). Moreover, among the isolated alkaloid lycopodine, acetyldihydrolycopodine, cernuine, lycocernuine and clavolonine, only acetyldihydrolycopodine and cernuine possess an important inhibition, and none significantly inhibited butyrylcholinesterase. It was also assessed the anticholinesterase effect for the alkaloidal extracts of L. clavatum and L. thyoides employing cortex, hippocampus and striatum rat brain homogenates as enzymatic sources, being determined the incubation time-inhibition curves over a concentrations range. It was also verified for both extracts an inhibitory effect of the competitive/non competitive mixed type, as well as their in vitro antioxidant profile using the methods of DPPH radical decoloration, 2-deoxyrribose degradation, TRAP and nitric oxide. After an acute treatment in 14 months-aged mice, we verified the antioxidant effects though TBA-RS and also the enzymes catalase and superoxide dismutase. In the same way, we found out that the same extracts reduced the acetylcholinesterase activity when administered by intraperitoneal injection. Using this methodology, the most potent extracts were H. quadrifariata and H. reflexa, corroborating the in vitro effect found for them. The purified alkaloidal extracts of L. clavatum and L. thyoides with habitat in Brazil and Argentine were compared to their chemical and biological profile. In this study, we found out that lycopodine and acetyldihydrolycopodine are the main alkaloids found for all species, and L. clavatum possesses a better inhibition against AChE when compared to L. thyoides for both Brazilian and Argentinean collected species.

Introdução: Indíviduos com danos cerebrais podem apresentar dissociação na produção de verbos e substantivos. Há uma maior diversidade de transtornos neurológicos que apresentam prejuízo na produção de verbos do que de substantivos, e esses transtornos normalmente apresentam danos em circuitos cerebrais frontais. No entanto, pouco se sabe sobre a natureza do prejuízo na produção de verbos em cada transtorno neurológico. Objetivo: A presente tese de doutorado teve como objetivo investigar a produção de verbos em diferentes doenças neurodegenerativas e no envelhecimento normal através das tarefas de fluência e nomeação de verbos. Métodos: para atingir o objetivo geral, foram realizados três estudos que originaram três artigos científicos. O primeiro artigo realizou uma adaptação da tarefa de fluência de verbos para o português brasileiro, obteve a performance de 62 brasileiros idosos saudáveis para esta tarefa e a influência de fatores demográficos, clínicos e da aplicação de outras tarefas de fluência verbal previamente à fluência de verbos. O segundo artigo investigou a natureza dos déficits da produção de verbos na doença de Alzheimer (DA). Para isso 35 pacientes com DA em fase leve e moderada foram avaliados para as tarefas de fluência e nomeação de verbos, assim como 35 idosos saudáveis (controles). Também analisou-se a influência da frequência das palavras nas tarefas estudadas. O terceiro artigo, investigou a natureza dos déficits na produção de verbos na Afasia Progressiva Primária (APP) não-fluente. Foram avaliados 12 pacientes com APP não-fluente e 9 sujeitos controle. Todos partcipantes foram avaliados através de tarefas de nomeação e fluência de verbos e de substantivos. Um efeito de manipulabilidade foi estudado na tarefa de nomeação. Correlatos neurais foram investigados utilizado a técnica de Voxel Based Morphometry (VBM) a partir de imagens de ressonância magnética (RM) estrutural dos pacientes. Resultados: No primeiro artigo obteve-se a performance dos idosos saudáveis na fluência de verbos (11,73±5,80), a correlação com a escolaridade (r=0,616), MEEM escore total (r=0,399), MEEM Atenção e Cálculo (r=0,393), e MEEM Linguagem (r=0,322). Não houve influência da aplicação prévia de tarefas de fluência verbal na fuência de verbos. No segundo artigo, os pacientes com DA mostraram prejuízo tanto na tarefa de nomeação de verbos (p<0,000; F=36,983) quanto na fluência de verbos (p<0,000; F=21,460), porém a primeira foi mais comprometida que a segunda. A performance dos pacientes com DA na nomeação de verbos foi influenciada pela severidade da doença e pela frequência das palavras. No terceiro artigo, os pacientes com APP não-fluente foram comprometidos em todas tarefas de nomeação e de fluência verbal, porém foram significativamente piores em verbos do que em substantivos. Não houve efeito de manipulabilidade. As áreas atróficas Broadmann 44 (p<0,001) e giro pré-central (p<0,001) se correlacionaram com o prejuízo na nomeação de verbos, enquanto as áreas atróficas 44 e 45 de Broadman (p<0,001, ambas) se correlacionaram com o prejuízo na fluência de verbos. Conclusões: Nossos achados indicam que o prejuízo na produção de verbos parece ter uma natureza predominantemente semântica na DA e prodominantemente gramatical na APP não fluente. As evidências levantam questões importantes também para a neurobiologia da linguagem. / Background: Individuals with brain damage may show dissociation in the verb and noun production. There is a larger diversity of neurological disorders that show impairment in verbs rather in nouns, and these disorders use to present damage in the frontal brain circuits. However, little is known about the nature of the verb production impairment in each one of these neurological disorders. Objective: The current doctoral thesis had the aim of investigating the verb production in different neurodegenerative diseases and in the normal elderly, using verb fluency and verb naming tasks. Methods: to reach the main aim, we carried out three studies that resulted in three articles. In the first article we adapted the verb fluency task for Brazilian Portuguese, we obtained the performance of 62 healthy elderly people for this task, and we verified the influence of demographic and clinical factors as well as of the previous application of other verbal fluency tasks. The second article investigated the nature of the verb production deficits in the Alzheimer’s disease (AD). Thirty-five mild and moderate AD patients and 35 healthy controls were evaluated for verb fluency and verb naming tasks. It also analyzed the influence of word frequency in the used tasks. The third article investigated the nature of verb production deficits in the nonfluent variant of Primary Progressive Aphasia (nfPPA). Twelve patients with nfPPA and 9 healthy controls were evaluated for verb and noun fluency and naming tasks. A manipulability effect was studied in the naming task. Neural correlates were investigated by Voxel Based Morphometry (VBM) of structural Magnetic Ressonance Imaging (MRI) of the patients. Results: The first article obtained the healthy elderly people performance for verb fluency (11.73±5.80), a correlation with education (r=0.616), MMSE total score (r=0.399), MMSE Attention and Calculation (r=0.393), and with MMSE Language (r=0.322). There was no influence of previous application of verbal fluency tasks on the verb fluency. In the second article, the AD patients showed deficits in the verb naming (p<0.000; F=36.983) and in the verb fluency (p<0.000; F=21.460), however the first task was more impaired than the second one. The AD patients performance in the verb naming was influenced by the disease severity and by word frequency. In the third article, the nfPPA patients were impaired in all naming and fluency tasks, however they were significantly worse in verbs than in nouns. There was no effect of manipulability. Atrophy on BA 44 (p<0.001) and on precentral gyrus (p<0.001) correlated with impairment in verb naming. Atrophy on BA 44 and 45 (p<0.001 for both) correlated with impairment in verb fluency. Conclusions: Our findings indicate the verb production deficits seem to have a more predominant semantic nature in AD and more predominant grammatical nature in nfPPA. This evidence brings up important questions for the neurobiology of language.

The possibility that lifestyle factors may delay or accelerate cognitive decline in aging has garnered significant attention and a considerable body of research has formed. However, investigating the relations between social engagement and cognitive function in aging have been somewhat equivocal in their findings and there is a lack of understanding of the mechanisms by which social engagement may impact cognitive function and the role of factors limiting social engagement. The aim of this dissertation was to build on current understanding of how specific aspects of social relationships relate to cognitive functioning in older adulthood and how these aspects are affected by challenges and barriers to social participation. This dissertation is comprised of three studies addressing several specific research questions. Study one (Chapter 2) examined whether relations with cognitive performance over time differ for structural aspects of social relationships (social network and social contact) versus functional/subjective aspects of social relationships (loneliness and social support) and whether the associations are between cognitive performance and stable, “trait-like” components of social relationships or fluctuating “state-like” components of these constructs, using autoregressive latent trajectory modeling of data from the Health and Retirement Study. Study two (Chapter 3) used a multilevel modeling approach to examine whether the spouses/partners of individuals diagnosed with Alzheimer’s disease or dementia experience a within person decline in cognitive performance and whether changes in structural and functional/subjective aspects of social relationships interacted with a spouses’ diagnosis of memory disease to predict within person change in cognitive performance. Study three (Chapter 4) investigated whether rejection sensitivity, social avoidance, and fears of negative social evaluations were predictive of lack of social participation and loneliness in a sample of Vancouver Island older adults. These factors have previously been investigated in younger adults as risk factors for loneliness and social withdrawal, but social isolation in older adulthood is often attributed to lack of social opportunities. This dissertation demonstrates the importance of considering precise aspects of social relationships, including barriers to social participation, and their relations to cognitive functioning. / Graduate / 2019-12-12