With the growing older adult population, neurodegenerative diseases common in old age such as mild cognitive impairment (MCI) or Parkinson’s disease (PD) are becoming increasingly germane areas of research. Pharmacological treatments have thus far been unsuccessful in treating cognitive decline associated with these neurodegenerative disorders. Alternative interventions, such as cognitive training programs, have shown promise. The current dissertation contains three papers examining cognitive interventions in neurodegenerative diseases. The first paper examined the longitudinal effects of cognitive speed of processing training (SPT) among those with PD. Results showed that training gains seen at initial post-test were maintained three months later. The second paper examined the effects of SPT among those with psychometrically-defined MCI and found small to medium effect sizes for improvements in everyday functional performance among those trained. The third paper examined the effects of auditory cognitive training among cognitively healthy older adults and those with psychometrically-defined MCI and found that effects may differ between those with and with MCI. Overall, these papers show that training effects can be maintained longitudinally and may potentially transfer to everyday functioning in those with neurodegenerative diseases. However, not all cognitive training programs show benefits in all areas, and individuals with differing cognitive statuses may benefit differentially from cognitive training. Future research should further explore the longitudinal effects of these training programs as well as the possibility of transfer to untrained abilities.

Charles Bonnet syndrome (CBS) is defined as complex persistent visual hallucinations in the absence of mental disorder. It is associated with advanced age and poor vision. It is common, with prevalence estimates of up to 63% among older people with significant visual impairment. CBS would not be diagnosed in the presence of dementia, but its relationship to milder cognitive impairment is unclear. The few studies that have examined this are underpowered and provide contradictory results. There are 16 case reports of dementia emerging in people with a diagnosis of CBS. These cases raise the possibility of an association between impaired insight at diagnosis of CBS and the subsequent development of dementia. This thesis reports the findings of a prospective cohort study which describes changes in cognitive functioning over one year in patients with CBS and age-matched controls. Participants were recruited from low vision and glaucoma assessment clinics. A clinical assessment was carried out by an old age psychiatrist, and participants had a detailed assessment of visual functioning. This thesis also describes the findings of the first study to use voxel-based morphometry (VBM) to investigate changes in volume of grey and white matter in CBS. Participants were recruited from the same clinics as the cohort study, and underwent MRI scanning on a 1.5T scanner, to a protocol designed to produce 1mm3 voxels. Twelve participants with CBS and ten controls were followed up. Two people in the CBS group developed dementia, while none did in the control group. The CBS group showed a mean change in the score on the Addenbrooke’s cognitive examination (ACE-R) of -3.7 points, compared to a change of +1.4 in the control group. This difference was not statistically significant. The CBS participants performed worse on the verbal fluency item of the ACE-R, a difference which was statistically significant. The VBM analysis was conducted on 11 CBS participants and 11 controls. The CBS group showed an increase in grey matter volume in the right cerebellar hemisphere. This difference retained significance after family-wise error correction, non-stationary correction, and ANCOVA to control for the effects of possible confounders. As far as the author is aware, these are the most methodologically robust studies to date to have investigated cognition and morphological brain changes in CBS. The findings of the cohort study were inconclusive. However, the two cases of dementia in CBS patients add weight to the suspicion that this is a clinically important outcome in the condition, and the finding of abnormalities in frontal lobe testing in participants with CBS fits with a theoretical model of visual hallucination generation. Moreover, this type of research appears to be acceptable to a frail and visually disabled population, and studies powered to investigate this issue more fully would be feasible. The VBM findings report the presence of underlying structural brain abnormalities in CBS, in a region not usually associated with visual hallucinations. Possible links with Lewy body dementia, and implications for theories of visual hallucinations, are discussed.

Performance on the Spatial Span subtest of the Wechsler Memory Scale has been viewed as an indicator of working memory and visuospatial processing. A number of factors including age and gender have been posited to effect performance on Spatial Span by older adults. The current study examined the impact of various forms of cognitive impairment and severity of impairment on Spatial Span performance. Five hundred thirty-eight individuals between the ages of 65 and 89 were evaluated in a university memory disorders clinic using a battery of neuropsychological tests that included Spatial Span. Participants were grouped by consensus diagnosis into type of cognitive impairment (Alzheimer's disease, vascular disease, amnestic mild cognitive impairment or non-amnestic mild cognitive impairment) or cognitively normal. As expected, an increase in severity of impairment results in a decrease in Spatial Span Total Score. Other findings included a weak relationship between age and Spatial Span Total Score. Gender, as well as age, did not fully account for the decline in Spatial Span Total Score. Spatial Span Forward score was not as good a predictor of severity in that reduction in score for Spatial Span Forward remains relatively stable regardless of level of impairment. Spatial Span Backward performance was found to be more sensitive to severity. No significant differences were found between performance of Alzheimer's disease and vascular disease suggesting they share similar deficit patterns with regard to the cognitive abilities measured by the Spatial Span subtest. A comparison between those diagnosed with mild cognitive impairment and individuals without such a diagnosis showed no significant difference suggesting that visuospatial processes are not affected early in the dementing process.

Orientador: Paulo José Fortes Villas Boas / Resumo: Introdução: Há poucos estudos com qualidade metodológica que avaliam o perfil dos idosos institucionalizados, porém, estes observam alta prevalência de déficit cognitivo. Conhecer a prevalência de déficit cognitivo desta população poderá ampliar as discussões acerca da necessidade de estruturação da rede de cuidados. Objetivo: Avaliar a prevalência de déficit cognitivo em idosos residentes em Instituição de Longa Permanência. Métodos: Estudo transversal realizado entre maio de 2018 e janeiro de 2019, no Lar Padre Euclides, em Botucatu. Foi realizada avaliação quanto a capacidade funcional (escalas de Katz, Lawton e Pfeffer), cognição (Mini Exame do Estado Mental - MEEM) e sintomas depressivos (Escala de Depressão Geriátrica - GDS). Portadores de demência foram classificados quanto a gravidade pelo Clinical Dementia Rating (CDR). Foram realizadas análises descritivas, testes de associação (teste Exato de Fisher e t-Student) e de correlação (teste de Pearson), sendo estatisticamente significativo quando p-valor < 0,05. Resultados: A amostra avaliada foi de 52 idosos, com média de idade de 77,90 (± 8,82) anos, 55,8% do sexo feminino. 96,2% (n=50) apresentavam déficit cognitivo pelo MEEM, sendo que apenas 30% (n=15) possuíam o diagnóstico prévio de demência. Dos 35 portadores de déficit cognitivo sem diagnóstico prévio, 77,1% apresentavam algum grau de dependência funcional. Dentre os portadores de demência (n=15), 60% estavam em estágios moderados ou graves, segundo o CDR. 41 id... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Introduction: There are few studies with methodological quality that assess the institutionalized elderly profile, but they observe a high prevalence of cognitive impairment. Knowing the prevalence of cognitive impairment in this population may increase the discussions about the need to structure the care network. Objective: To explore the prevalence of cognitive impairment in residents at home for the aged. Methods: Cross-sectional study conducted between May 2018 and January 2019 at Padre Euclides Home in Botucatu. Functional capacity (Katz, Lawton and Pfeffer scales), cognition (Mental State Mini Examination - MMSE) and depressive symptoms (Geriatric Depression Scale - GDS) were evaluated. Dementia carriers were classified as severity by the Clinical Dementia Rating (CDR). Descriptive analyzes, association (Fisher's exact test and t-Student) and correlation tests (Pearson test) were performed, being statistically significant when p-value < 0,05. Results: Fifty-two elderly individuals were evaluated, with an average age of 77,90 (± 8,82) years, 55,8% female. 96,2% (n = 50) presented cognitive impairment by MMSE, and only 30% (n = 15) had previous diagnosis of dementia. About 35 patients with cognitive impairment without previous diagnosis, 77,1% had some degree of functional dependence. Among those with dementia (n = 15), 60% were in moderate or severe stages, according to CDR. 41 elderly people with cognitive impairment were evaluated with GDS, and of these, 36,5% presente... (Complete abstract click electronic access below) / Mestre

The rate of cancer patients is increasing as the development of science and technology. Twenty million cancer survivors are estimated living in the United States by 2025. However, many cancer survivors show cognitive dysfunction, negatively affecting the quality of life. These cognitive impairments are recognized as chemotherapy-induced cognitive impairment (CICI), also called "chemo brain" by cancer survivors, including the diminished ability of memory and learning, hard to concentrate and focus, as well as diminution of executive function and processing speed. The etiologies and pathologies of CICI are complicated, especially in most cases the anti-cancer drug cannot cross the blood-brain barrier (BBB). One of the significant candidate mechanisms underlying CICI is chemotherapy-induced, oxidative damage-mediated tumor necrosis factor-alpha (TNF-a) elevation. One of the prototypes of reactive oxygen species (ROS)-generating chemotherapeutic agents is Doxorubicin, normally used as part of multi-drug chemotherapeutic regimens to treat solid tumors and lymphomas. In this dissertation, TNF-a null (TNFKO) mice were used to investigate the role of TNF-a in Dox-induced, oxidative damage-mediated alterations in brain. Dox-induced oxidative damage in brain is ameliorated and brain mitochondrial function is preserved in brains of TNFKO mice. Both Dox-decreased levels of hippocampal choline-containing compounds and activities of brain phospholipases are partially protected in the TNFKO group. It is shown in this dissertation that Dox-targeted mitochondrial damage and levels of brain choline-containing metabolites, as well as changes in the activity of phospholipases, including both phosphatidylcholine-specific phospholipase C (PC-PLC) and phospholipase D (PLD), are decreased in the CNS and associated with oxidative damage mediated by TNF-a. The results are discussed with respect to identifying a potential therapeutic target to protect against cognitive problems after chemotherapy and thereby improve the quality of life of cancer survivors. We also tested the effect of a chemotherapy drug adjuvant, 2-mercaptoethane sulfonate sodium (MESNA), on CICI in this dissertation research. MESNA ameliorated Dox-induced oxidative protein damage in plasma and led to decreased oxidative damage in brain. MESNA was demonstrated to rescue the memory deficits caused by Dox in the novel object recognition test. The activity of PC-PLC was preserved when MESNA was co-administered with Dox. This study is the first evidence for demonstrating the protective effects of MESNA on Dox-related protein oxidation, cognitive decline, phosphocholine levels, and PC-PLC activity in brain and suggests novel potential therapeutic targets and strategies to mitigate CICI. Parkinson Disease (PD) is considered as the second most neurodegenerative disease, associated with aging and gender. Although the detailed mechanisms remain unknown, inflammation and oxidative damage are two main etiological factors of PD. Certain genetic factors have been discovered related to this disease. Thus, using rodent models with relative gene mutations are the main strategies to investigate PD. However, few rodent models showed same clinical and biochemical features of PD. PTEN-induced putative kinase -1 (PINK1) knockout (KO) rat is the rodent model used in this dissertation research. The oxidative damage in the brain of PINK1 KO rats, the ventricle sizes, and neurochemical metabolite profiles in these rats as a function of age and gender were measured. Distinct gender- and age-related alterations were found, many consistent with those in PD. The proteome of brain of PINK1 KO rat as a function of age and gender also was studied. Based on the collected data, the suitability of this unique rat as a faithful model of known characteristics of PD with our results is discussed.

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Designing with and for People with Dementia: Wellbeing, Empowerment and Happiness is the International Conference 2019 of the MinD Consortium, the DRS Special Interest Group on Behaviour Change and the DRS Special Interest Group on Wellbeing and Happiness, hosted by the Technische Universität Dresden, in Dresden, Germany. The conference proceedings provide trans-disciplinary contributions for researchers, practitioners, end-users and policy makers from the design and health care professions in terms of new findings, approaches and methods for using design to improve dementia care and to support people with dementia and their carers. The conference has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 691001, and from the DFG German Research Foundation.

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Background: Parkinson’s disease (PD) is a progressive neurodegenerative motor disorder. However, non-motor complications frequently alter the course of the disease. A particularly disabling non-motor symptom is dementia. Methods/Design: The study is designed as a multicentre prospective, observational cohort study of about 700 PD patients aged 45–80 years with or without dementia and PD-mild cognitive impairment (MCI). The patients will be recruited in eight specialized movement disorder clinics and will be followed for 36 months. Information about the patients’ functional status will be assessed at baseline and 6-/12- month intervals. In addition, 120 patients with dementia with Lewy bodies (DLB) will be included. Well-established standardized questionnaires/tests will be applied for detailed neuropsychological assessment. In addition, patients will be asked to participate in modules including volumetric MRI, genetic parameters, and neuropsychology to detect risk factors, early diagnostic biomarkers and predictors for dementia in PD. Results: The study included 604 PD patients by March 2011; 56.3% were classified as having PD alone, with 30.6% of patients suffering from PD-MCI and 13.1% from PD with dementia. The mean age of the cohort was 68.6 ± 7.9 years, with a mean disease duration of 6.8 ± 5.4 years. There was a preponderance of patients in the earlier Hoehn and Yahr stages. Conclusion: The main aim of the study is to characterize the natural progression of cognitive impairment in PD and to identify factors which contribute to the evolution and/or progression of the cognitive impairment. To accomplish this aim we established a large cohort of PD patients without cognitive dysfunction, PD patients with MCI, and PD patients with dementia, to characterize these patients in a standardized manner, using imaging (serial structural MRI), genetic and proteomic methods in order to improve our understanding of the course of the PD process and the development of cognitive dysfunction and dementia in this disease. The inclusion of the DLB patients will start in the second quarter of 2011 in the BMBF-funded follow-up project LANDSCAPE.

The global population with dementia is rapidly increasing around the world.The major risk factor for dementia is aging. There is currently no treatmentavailable and the cost of symptomatic treatment is high. There is a growinginterest in possible clinical applications of non-invasive methods that are safeand easy-to-perform in diagnosis of dementia. The purpose of this paper is toinvestigate the usage of transcranial magnetic stimulation (TMS) withelectroencephalography (EEG) to diagnose dementia in early stages of thedisease. Early diagnosis is needed to reduce the costs of symptomatic care.When investigating the usage of TMS-EEG technology, we will look at how wecan distinguish dementia in different neurodegenerative diseases between eachother. More research is needed to suggest an accurate parameters fordiagnosis of dementia with this type of technology.