INTRODUÇÃO: Estudos recentes mostram que fatores cognitivos podem estar relacionados ao desempenho motor em pacientes com doença de Parkinson (DP). Aspectos motores, como o equilíbrio e a marcha, e aspectos cognitivos (função executiva) podem ser usados para estimar o risco de quedas, que são causadas tanto por instabilidade postural, quanto por disfunções executivas em pacientes com DP. Entretanto, a correlação entre escolaridade, função executiva, equilíbrio estático, equilíbrio dinâmico e marcha permanece pouco explorada. OBJETIVO: O objetivo desse estudo foi verificar se há correlação entre variáveis cognitivas (escolaridade, função executiva) e motoras (Escala de Berg, MiniBESTest, Timed Up and Go Test (TUG), TUG Dupla Tarefa (DT), UPDRS - III, posturografias estática e dinâmica) em pacientes com DP. MÉTODOS: Setenta e um pacientes com DP participaram deste estudo. Os participantes relataram seu tempo de estudo formal. Para a avaliação da função cognitiva dos participantes, foram usandos o Trail Making Test e o teste de Fluência Verbal. A avaliação do equilíbrio funcional foi realizada por meio da Escala de Equilíbrio de Berg e do MiniBESTest. A avaliação da marcha foi realizada com o TUG e TUG DT. A posturografia estática foi utilizada para quantificar os deslocamentos do centro de pressão (COP), como medida de equilíbrio estático. A posturografia dinâmica permitiu avaliar o controle postural, enquanto os participantes fizeram algumas tarefas que exigiam equilíbrio. RESULTADOS: Os coeficientes de correlação de Pearson indicaram que houve correlações moderadas entre a escolaridade e aspectos motores (todas as escalas clínicas de equilíbrio e marcha). Houve correlação moderada entre função executiva e aspectos motores (ambas as escalas clínicas de equilíbrio). Houve correlação moderada entre a posturografia dinâmica e o TUG e TUG DT. CONCLUSÃO: Houve correlação entre aspectos cognitivos (escolaridade, função executiva) e motores (Escala de Equilíbrio de Berg, MiniBESTest, TUG, TUG DT e UPDRS - III) nos pacientes com DP. Apenas a posturografia dinâmica esteve correlacionada com os testes clínicos / BACKGROUND: Recent studies have shown that cognitive factors can be related to motor performance in patients with Parkinson disease (PD). Motor aspects, such as balance and gait and cognitive aspects (executive function) can be used to estimate the risk of falls, which are caused by postural instability and executive dysfunction in patients with PD. However, the correlation between educational status, executive function, static balance, dynamic balance and gait remains poorly explored. OBJECTIVE: The aim of this study was to verify if there would be correlation between cognitive variables (educational status, executive function) and motor variables (Berg balance scale, MiniBESTest, Timed Up and Go (TUG) TUG dual task (DT), UDPRS - III, static and dynamic posturography) in patients with PD. METHODS: Seventy patients with PD participated in this study. Participants reported their time of formal education. They were assessed with Trail Making Test and verbal fluency test (cognitive assessment). Fuctional balance evaluation was performed by Berg balance scale, MiniBESTest and UPDRS- III. Gait was assessed with TUG, and TUG DT. Static posturography was used to quantify the center of pressure displacement (CoP). RESULTS: Pearson correlation coefficients indicated that there were moderate correlations between education and motor aspects (all balance and gait clinical scales). There was moderate correlation between executive function and motor aspects (both clinical balance scales). There was moderate correlation between verbal fluency and balance (balance scales and dynamic posturography). CONCLUSION: There was correlation between cognitive (education, executive function) and motor aspects (Berg balance scale, MiniBESTest, TUG, TUG DT and UDPDS- III), in patients with PD. Only dynamic posturography was correlated to clinical balance tests

初級運動皮質直接負責運動控制。大量關於帕金森式癥(PD)的有效治療手段的研究已經證明，初級運動皮質在病理情況下的功能改變，直接與患者運動障礙相關。本論文的研究重點在於探索初級運動皮質在深部腦刺激治療帕金森氏症的運動障礙的過程中發揮的作用及其與運動學習功能障礙的聯繫。 / 丘腦底核深部腦刺激(STN-DBS) 已被廣泛應用於治療帕金森式症。雖然該項治療手段能顯著地改善患者的運動功能障礙，但其確切的治療機制仍未明確。理論上來說，丘腦底核深部腦刺激能夠直接啟動丘腦底核內部和其周圍很大範圍的神經組織，包括丘腦底核內部本身的神經元胞體，以及與其相連接的輸入輸出核團的神經元軸突。在丘腦底核眾多輸入核團之中，一個重要的神經輸入來自於初級運動皮質(MI)第五層的離皮質神經元(CxFn)，電刺激引起的逆行皮質啟動作用被提出，用於解釋丘腦底核深部腦刺激的治療機制。 / 為了研究逆行皮質啟動效應究竟如何在丘腦底核深部腦刺激的過程之中帶來治療效果，我們採用多通道神經電生理信號記錄系統在自由活動的單側帕金森大鼠的初級運動皮質進行鋒電位元和局部場電位元信號的記錄。實驗結果證明，當對丘腦底核進行高頻電刺激，在運動皮質第五層的離皮質神經元能成功記錄到保持固定延時的逆行鋒電位。由於增加刺激頻率會引起逆行鋒電位被成功記錄到的百分比下降，因此當深部腦刺激的頻率選擇在125Hz時，逆行鋒電位的放電頻率達到最高，而此刺激頻率正好與行為學實驗中帶來最佳治療效果的刺激頻率一致。於此同時，逆行皮質啟動作用還伴隨著初級運動皮質離皮質神經元的自發放電頻率增加、同步性爆發式放電減少等電生理信號特點。場電位分析的結果進一步表明，丘腦底核深部腦刺激減弱了病理情況下出現的beta波頻譜能量增高以及鋒電位-場電位相干性增強。更重要的是，我們發現只有逆行鋒電位被成功誘發，離皮質神經元的發放電機率才能被調節。這點有力地表明由電刺激隨機誘發的逆行鋒電位傳導至初級運動皮質，直接幹預並抑制了離皮質神經元在病理情況下的同步性爆發式放電活動，從而緩解了帕金森氏症的運動障礙。 / 另外，初級運動皮質並不僅僅是一個靜態的運動控制中樞，更為重要的功能在於它參與著與運動學習和運動記憶相關的動態資訊編碼。帕金森氏症患者普遍存在皮質可塑性減弱以及運動技能學習障礙。由於初級運動皮質分層結構的存在，層內神經元之間的突觸連接為神經可塑性提供了很好的結構基礎。因此，我們在初級運動皮質誘發在體長時程增強(LTP)，旨在研究與運動技能學習相關的皮質神經可塑性的動態變化過程，以及探索中腦多巴胺能投射系統對皮質神經可塑性的影響。 / 一方面，我們採用間斷性高頻刺激誘發在體長時程增強，證實六羥多巴損毀後皮質的長時程增強水準顯著下降。另一方面，我們設計前肢抓食的行為學範式用來評價動物在運動技能學習的不同階段皮質可塑性發生的動態變化。實驗結果表明，直接損毀皮質的多巴胺能輸入，模型組大鼠與假實驗組大鼠的行為表現在初期的技能獲取階段並無明顯差異，而只在後期的技能鞏固階段模型組大鼠表現出技能鞏固障礙。更為有趣的是，兩組行為學變化趨勢與各自的在體長時程增強的變化趨勢有很高的一致性。本研究表明多巴胺對初級運動皮質的支配在運動記憶的鞏固過程中起著關鍵作用。在帕金森氏症的病理情況下，多巴胺耗竭將影響皮質的突觸可塑性，從而造成帕金森患者在運動技能的鞏固階段表現出障礙。 / The primary motor cortex (MI) controls movement directly, but is an under-investigated brain region in the pathogenesis and treatment of Parkinsonian motor disability, when compared with the basal ganglia circuitry. In this study, the roles of MI in underlying the therapeutic action of surgical deep brain stimulation and motor learning impairment were investigated. / Deep brain stimulation of the subthalamic nucleus (STN-DBS) is now a recognized therapeutic option for Parkinson’s disease (PD). Although this surgical strategy provides behavioral benefits remarkably, its exact mechanism is still a matter of controversy. In principle, STN-DBS can directly activate a wide range of neuronal elements within the STN and surrounding areas. As the corticofugal neurons (CxFn) in the layer V motor cortex provide a major input to the STN, we hypothesized that the stimulation evoked antidromic cortical activation is involved in the therapeutic mechanism of STN-DBS. In the first series of experiments, we performed simultaneous recordings of multi-unit neuronal activities and local field potentials (LFPs) in MI in freely moving hemi-parkinsonian rats. By identifying stimulation evoked antidromic spike, which occurred at a fixed, short latency, CxFn located in the layer V MI were identified. Increasing stimulation frequency also increased failure rate of activation, resulting in a peak frequency of stochastic antidromic spikes at 125Hz STN-DBS, which was correlated with the optimal therapeutic efficacy observed in behavioral tests. Meanwhile, this antidromic effect was accompanied by the rectification of pathological neuronal activities including increased spontaneous firing rate, reduced burst discharge and synchrony among the CxFn. Field potential analysis revealed that STN-DBS alleviated the dominance of pathological beta band oscillation and spike-field coherence in the MI. More importantly, it was found that the firing probability of CxFn could only be modified following the occurrence of antidromic spikes, suggesting that direct interference of stochastic antidromic spikes with pathological neuronal activities underlies the beneficial effect of STN-DBS. / The MI is not simply a static motor control structure. It also contains a dynamic substrate that participates in motor learning or stores motor memory. In PD patients, loss of cortical plasticity and impaired motor learning is a common feature. As the intrinsic horizontal neuronal connections in MI are a strong candidate of cellular correlate for activity-dependent plasticity, in the second series of experiments, we developed in vivo long-term potentiation (LTP) technique in the MI to investigate the dynamics of cortical plasticity during motor skill learning and the role of the innervation by mesocortical dopamine input. Local depletion of dopamine in the primary motor cortex resulted in reduced performance in the forelimb reaching for food learning task. Although the performance of the PD rats in the initial learning phase was comparable to that of the sham-operated group, as training continued, these animals exhibited deficit in consolidating the motor skill. These deficits closely paralleled the impairment in training-enhanced synaptic connections in layer V neurons, and the in vivo LTP of evoked field excitatory postsynaptic potentials induced by intermittent high frequency stimulation. In addition, progressive recruitment of task-specific neurons was suppressed. Our study therefore revealed that dopamine depletion confined to the MI could lead to impairment in cortical synaptic plasticity which may preferentially affect the consolidation, but not the acquisition, of motor skills. These findings shed light on the cellular mechanisms of motor skill learning and could explain the decreased ability of PD patients in learning new motor skills. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Li, Qian. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 168-190). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts also in Chinese. / CHAPTER 1 --- p.1 / General Introduction --- p.1 / Chapter 1.1 --- Anatomical organization of the basal ganglia --- p.1 / Chapter 1.1.1 --- Overview of the basal ganglia circuit --- p.1 / Chapter 1.1.2 --- Cortico-basal ganglia-cortical circuit --- p.1 / Chapter 1.1.2.1 --- Direct and indirect pathway --- p.2 / Chapter 1.1.2.2 --- Hyperdirect pathway --- p.2 / Chapter 1.1.2.3 --- The midbrain dopamine system --- p.2 / Chapter 1.2 --- Striatum --- p.3 / Chapter 1.2.1 --- Cell types in the striatum. --- p.3 / Chapter 1.2.2 --- The Cortico-striatal system --- p.4 / Chapter 1.3 --- Subthalamic Nucleus --- p.5 / Chapter 1.3.1 --- Neuronal property of the STN. --- p.5 / Chapter 1.3.2 --- Electrophysiological property of the STN --- p.6 / Chapter 1.3.3 --- Cortico-subthalamic system --- p.7 / Chapter 1.3.4 --- Functional significance of the cortico-subthalamic and corticostriatal system. --- p.8 / Chapter 1.4 --- Parkinson’s disease --- p.9 / Chapter 1.4.1 --- Pathogenesis of PD --- p.9 / Chapter 1.4.2 --- Genetic risk factors of PD --- p.10 / Chapter 1.4.3 --- Progressive motor symptoms of PD --- p.11 / Chapter 1.4.4 --- Non-motor symptoms of PD --- p.13 / Chapter 1.4.5 --- Pathological neuronal rhythms in the basal ganglia of PD. --- p.16 / Chapter 1.5 --- Experimental studies of PD. --- p.18 / Chapter 1.5.1 --- Animal modeling of PD. --- p.18 / Chapter 1.5.2 --- Motor deficits evaluation in rodent models of PD --- p.21 / Chapter 1.5.3 --- Non-motor symptoms evaluation in experimental models of PD --- p.24 / Chapter 1.6 --- Deep Brain Stimulation --- p.27 / Chapter 1.6.1 --- DBS in alleviating Parkinsonian motor symptoms --- p.28 / Chapter 1.6.2 --- DBS in alleviating Parkinsonian non-motor symptoms --- p.29 / Chapter 1.6.3 --- Investigation of the STN-DBS mechanism. --- p.31 / Chapter 1.6.3.1 --- Local inhibitory effect within the STN --- p.32 / Chapter 1.6.3.2 --- Excitatory effect at output nuclei --- p.33 / Chapter 1.6.3.3 --- The de-coupling of soma and axons at system level --- p.34 / Chapter 1.6.3.4 --- Effects of DBS on abnormal rate or pattern --- p.35 / Chapter 1.6.3.5 --- Antidromic propagation of DBS effect towards cortex --- p.37 / Chapter 1.7 --- Objective --- p.38 / Chapter 1.8 --- Figures --- p.41 / CHAPTER 2 --- p.47 / General Methods --- p.47 / Chapter 2.1 --- Animals --- p.47 / Chapter 2.2 --- Stereotaxic surgery --- p.47 / Chapter 2.2.1 --- Preoperative preparation --- p.47 / Chapter 2.2.2 --- Anesthesia and craniotomy --- p.48 / Chapter 2.2.3 --- Induction of hemi-Parkinsonian rat model --- p.48 / Chapter 2.2.4 --- Electrode implantation techniques. --- p.49 / Chapter 2.3 --- Behavioral assessment. --- p.50 / Chapter 2.3.1 --- Apomorphine-induced contralateral rotation. --- p.50 / Chapter 2.3.2 --- Open field test --- p.50 / Chapter 2.4 --- STN-DBS protocol --- p.50 / Chapter 2.5 --- Electrophysiological data acquisition --- p.51 / Chapter 2.6 --- Data analysis --- p.52 / Chapter 2.6.1 --- Statistical analysis of behavioral data --- p.52 / Chapter 2.6.2 --- Electrophysiological data --- p.52 / Chapter 2.6.2.1 --- Stimulation artifact removal --- p.52 / Chapter 2.6.2.2 --- Multi-unit spike sorting --- p.53 / Chapter 2.6.2.3 --- Electrophysiological identification of pyramidal neuron and interneuron. --- p.54 / Chapter 2.6.2.4 --- Identification of antidromic cortical activation --- p.54 / Chapter 2.6.2.5 --- Discharge pattern classification --- p.54 / Chapter 2.6.2.6 --- Synchrony level evaluation --- p.55 / Chapter 2.6.2.7 --- Oscillatory rhythm characterization --- p.55 / Chapter 2.6.2.8 --- Coherence Level Measurement --- p.56 / Chapter 2.7 --- Histological verification --- p.56 / Chapter 2.8 --- Figures --- p.58 / CHAPTER 3 --- p.60 / Alleviation of Parkinsonian Motor Symptoms during Deep Brain Stimulation in Hemi-Parkinsonian Rats --- p.60 / Chapter 3.1 --- Introduction --- p.60 / Chapter 3.2 --- Materials & Methods --- p.61 / Chapter 3.2.1 --- Animals --- p.61 / Chapter 3.2.2 --- Chemicals --- p.61 / Chapter 3.2.3 --- Equipment --- p.61 / Chapter 3.3 --- Results --- p.62 / Chapter 3.3.1 --- Time course of the Apomorphine induced rotation behavior --- p.62 / Chapter 3.3.2 --- Dose-dependence of the Apomorphine induced rotation --- p.62 / Chapter 3.3.3 --- Acute behavioral response to STN-DBS. --- p.63 / Chapter 3.3.4 --- The dependence of STN-DBS effect on stimulation paradigm. --- p.64 / Chapter 3.3.5 --- Acute effects of STN-DBS on APO induced rotation. --- p.64 / Chapter 3.3.6 --- Long-term effects of STN-DBS on APO induced rotation --- p.64 / Chapter 3.3.7 --- Histological confirmation of the stimulation electrodes localization --- p.65 / Chapter 3.3.8 --- Loss of DA neurons in the SNc --- p.65 / Chapter 3.3.9 --- Reductions of the DA axon terminals in the striatum --- p.65 / Chapter 3.3.10 --- Chronic STN-DBS failed to rescue nigrostsriatal and striatal DA --- p.66 / Chapter 3.4 --- Discussion --- p.66 / Chapter 3.4.1 --- Neurotoxic mechanism of 6-OHDA --- p.66 / Chapter 3.4.2 --- Time course of dopamine degeneration induced by 6-OHDA --- p.66 / Chapter 3.4.3 --- Failure in observing worsened motor symptoms during low frequency STN-DBS. --- p.67 / Chapter 3.4.4 --- Experimental DBS based on rat model: does it mimic human case? --- p.67 / Chapter 3.4.5 --- Technical issues about STN-DBS --- p.69 / Chapter 3.5 --- Figures --- p.72 / CHAPTER 4 --- p.82 / Direct involvement of the Corticofugal Neurons in Motor Cortex during Therapeutic Deep Brain Stimulation --- p.82 / Chapter 4.1 --- Introduction --- p.82 / Chapter 4.2 --- Materials --- p.83 / Chapter 4.2.1 --- Animals --- p.83 / Chapter 4.2.2 --- Chemicals --- p.83 / Chapter 4.2.3 --- Equipment --- p.83 / Chapter 4.3 --- Results --- p.84 / Chapter 4.3.1 --- Identification of CxFn based on antidromic effect --- p.84 / Chapter 4.3.2 --- Antidromic spikes frequency correlates with therapeutic effect of STN-DBS. --- p.84 / Chapter 4.3.3 --- Pathological changes of neuronal firing rate in MI --- p.85 / Chapter 4.3.4 --- Only high frequency STN-DBS normalizes neuronal firing rate in MI --- p.86 / Chapter 4.3.5 --- Pathological changes of neuronal discharge pattern in MI --- p.88 / Chapter 4.3.6 --- Pathological synchrony of MI neuronal population, especially during burst discharge --- p.89 / Chapter 4.3.7 --- High frequency STN-DBS successfully suppresses synchronized burst discharge in MI --- p.89 / Chapter 4.3.8 --- Pathological β-band oscillatory activity in MI-LFPs induced by 6-OHDA lesion --- p.90 / Chapter 4.3.9 --- High frequency STN-DBS alleviates the β-band oscillation in MI-LFPs --- p.90 / Chapter 4.3.10 --- Synchronized bursting discharge correlates with oscillatory activity --- p.91 / Chapter 4.3.11 --- Pathological increased spike-LFP coherence level induced by 6-OHDA lesion --- p.92 / Chapter 4.3.12 --- High frequency STN-DBS modulated the spike-LFP coherence properties --- p.92 / Chapter 4.3.13 --- Antidromic spikes directly modulate the firing probability of CxFn --- p.93 / Chapter 4.3.14 --- Antidromic spikes modulate the firing probability of INs and non-CxFn nearby. --- p.94 / Chapter 4.3.15 --- The efficiency of antidromic cortical modulation depends on DBS frequency --- p.94 / Chapter 4.3.16 --- Orthodromic vs. antidromic effect: which one is responsible for the beneficial effect of DBS? --- p.95 / Chapter 4.3.17 --- Histology --- p.96 / Chapter 4.4 --- Discussion --- p.96 / Chapter 4.4.1 --- Origin of pathogenic rhythm in basal ganglia circuit --- p.96 / Chapter 4.4.2 --- Suppression of oscillatory synchronization equals to therapeutic effects of DBS? --- p.97 / Chapter 4.4.3 --- Beneficial effect of DBS corresponds to the topographic distribution of cortico-subthalamic projection. --- p.98 / Chapter 4.4.4 --- What is the reason for a stochastic pattern of antidromic activation effect? --- p.99 / Chapter 4.4.5 --- Desynchronization of pathological oscillatory rhythm by antidromic activation --- p.100 / Chapter 4.4.6 --- Antidromic vs. orthodromic: which is the cause of the beneficial effects of DBS? --- p.101 / Chapter 4.4.7 --- Wide propagation of antidromic effect by cortical horizontal circuits --- p.102 / Chapter 4.4.8 --- Significance of antidromic cortical activation in during STN-DBS --- p.102 / Chapter 4.4.9 --- Implication of antidromic activation effect on pathogenesis and treatment of PD --- p.104 / Chapter 4.5 --- Figures --- p.105 / CHAPTER 5 --- p.132 / Impaired Synaptic Plasticity in the Primary Motor Cortex after Dopamine Depletion: Potential Role in Motor Memory Consolidation --- p.132 / Chapter 5.1 --- Introduction --- p.132 / Chapter 5.1.1 --- Characteristics of motor learning --- p.132 / Chapter 5.1.2 --- Motor learning related cortical plasticity. --- p.133 / Chapter 5.1.3 --- Dopaminergic signals in the primary motor cortex --- p.134 / Chapter 5.1.4 --- Impaired cortical plasticity in PD --- p.135 / Chapter 5.1.5 --- Objective --- p.136 / Chapter 5.2 --- Materials --- p.136 / Chapter 5.2.1 --- Animals --- p.136 / Chapter 5.2.2 --- Chemicals --- p.136 / Chapter 5.2.3 --- Equipment --- p.136 / Chapter 5.3 --- Methods --- p.136 / Chapter 5.3.1 --- Functional mapping of the forelimb territory in MI --- p.136 / Chapter 5.3.2 --- Stereotaxic surgery --- p.137 / Chapter 5.3.3 --- Forelimb-reaching Task. --- p.137 / Chapter 5.3.4 --- In-vivo LTP Induction. --- p.138 / Chapter 5.4 --- Results --- p.139 / Chapter 5.4.1 --- Functional mapping of rat forelimb territory. --- p.139 / Chapter 5.4.2 --- Morphologies of evoked field potential response --- p.139 / Chapter 5.4.3 --- LTP of the early, monosynaptic plasticity within horizontal layer V MI --- p.140 / Chapter 5.4.4 --- LTP of the late, polysynaptic plasticity within horizontal layer V MI --- p.140 / Chapter 5.4.5 --- Impaired synaptic plasticity in MI after dopamine depletion --- p.140 / Chapter 5.4.6 --- Learning curve of forelimb-reaching task --- p.140 / Chapter 5.4.7 --- Physiologically enhanced cortical plasticity during motor learning --- p.141 / Chapter 5.4.8 --- Dynamic modulation of cortical neuronal activities during motor skill learning. --- p.142 / Chapter 5.4.9 --- Statistical analysis of ‘task related’ neuron’s modulation pattern. --- p.143 / Chapter 5.4.10 --- Loss of dopamine modulation in the MI --- p.144 / Chapter 5.5 --- Discussion --- p.144 / Chapter 5.5.1 --- Distinguishing between monosynaptic and polysynaptic transmission --- p.144 / Chapter 5.5.2 --- Artificially vs physiologically induced cortical plasticity. --- p.145 / Chapter 5.5.3 --- Cortical synaptic plasticity interprets motor learning dynamics --- p.146 / Chapter 5.5.4 --- Balance between neuronal recruitment and withdrawal in the consolidation stage --- p.147 / Chapter 5.5.5 --- Dopamine’s involvement in mediating the cortical synaptic plasticity. --- p.148 / Chapter 5.6 --- Figures --- p.150 / Conclusion --- p.162 / Abbreviations --- p.165 / References --- p.168

Made available in DSpace on 2016-04-27T18:11:49Z (GMT). No. of bitstreams: 1 Yole Cristina de Souza Neves.pdf: 813344 bytes, checksum: 05baee70664a9d5eca85cb6ebc9bad54 (MD5) Previous issue date: 2010-10-26 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Introduction: Parkinson's disease (PD) is a chronic and degenerative central nervous system that primarily affects individuals over 60 years. Studies have evaluated the PD and revealed negative impact on quality of life (QL). Purpouse: To investigate the association between QL and self-reported voice handicap in subjects with PD by means of two separate protocols. Method: The sample consisted of 32 subjects 18 men and 14 women with a diagnosis of PD between the stages 2, which included (9 subjects), 2,5 (eight subjects) and 3 (15 subjects) of Hoehn & Yahr (HY), and with a positive response to antiparkinsonian medication and the antiparkinsonian medication associated with antidepressant medication. Two questionnaires related QL were administered: the first one is the specific questionnaire called the QL in PD (PDQ-39); and the second is specific to QL related to voice, the voice handicap index (VHI). Results: The mean age of the subjects was 68,48 years, the time of disease 6,4 years. Nineteen subjects were the exclusive use of antiparkinsonian medication and 13 were using antiparkinsonian medication associated with the antidepressant. According to the responses from the questionnaire PDQ-39 we could verify that the mobility domain scores ranged from 23% until 100%, the variation in the ADL domain was from 25% until 100%, the field from emotional well-being ranged from 4% until 100%, the stigma was from 0 until 100%, the field social support ranged from 8% until 100%, in cognition the scores varied from 6% until 100%, the communication field ranged from 25% until 100%; in the area of bodily discomfort, the variation was from 13% until 100% and the total score ranged from 17% until 100%. Regarding the response obtained by questionnaire VHI we could verify that the organic domain scores ranged from 63% until 93% in the operational area ranging from 20% until 100%, in the emotional domain ranged from 10% until 100% and the total score ranged from 29% until 100%. With regard to drugs and the scale of HY was observed that subjects who have exclusive use of antiparkinsonian medication and were in HY stage 3 had higher scores on the PDQ-39 while the subjects who used antiparkinsonian medication, associated with antidepressant, and were in stage 3 HY showed higher scores in the VHI. Conclusion: Based on the results was observed the relationship between QL and voice in individuals with PD by means of two separate questionnaires / Introdução: a doença de Parkinson (DP) é uma afecção crônica e degenerativa do sistema nervoso central que afeta principalmente sujeitos acima de 60 anos. Estudos avaliaram que a DP revelou impacto negativo na qualidade de vida (QV). Objetivo: investigar, por meio de dois protocolos distintos, a associação entre QV e desvantagem vocal autorreferidas em sujeitos com DP. Método: a amostra foi composta por 32 sujeitos - 18 homens e 14 mulheres - com diagnóstico de DP entre os estágios 2, que compreendia (9 sujeitos), 2,5 (8 sujeitos) e 3 (15 sujeitos) da escala de Hoehn & Yahr (HY) e, com resposta positiva à medicação antiparkinsoniana bem como à medicação antiparkinsoniana associada antidepressiva . Foram aplicados 2 questionários relacionados a QV, sendo 1 específico a DP e denominado questionário de qualidade de vida na doença de Parkinson (PDQ-39) e, outro específico para QV relacionado à voz, o índice de desvantagem vocal (IDV). Resultados: a média de idade dos sujeitos da amostra foi de 68,48 anos, o tempo da doença de 6,4anos. Dezenove sujeitos faziam uso exclusivo da medicação antiparkinsoniana e 13 faziam uso da medicação antiparkinsoniana associada à antidepressiva. De acordo com as respostas obtidas no questionário PDQ-39 foi possível verificar que os escores no domínio mobilidade variou de 23% a 100%; no domínio AVD a variação foi de 25% a 100%; o domínio bem estar emocional variou de 4% a 100%; o estigma foi de 0 a 100%; o domínio apoio social variou de 8% a 100%; na cognição o escore variou de 6% a 100%; o domínio comunicação variou de 25% a 100%; no domínio desconforto corporal a variação foi de 13% a 100% e o escore total variou de 17% a 100%. Em relação às respostas obtidas pelo questionário IDV foi possível verificar que os escores no domínio orgânico variou de 63% a 93%; no domínio funcional variou de 20% a 100%, no domínio emocional variou de 10% a 100% e o escore total variou de 29% a 100%. No que se refere aos fármacos e a escala de HY observou-se que sujeitos que fizeram uso exclusivo da medicação antiparkinsoniana e encontravam-se no estágio 3 HY apresentaram escores mais elevados no PDQ-39 enquanto os sujeitos que fizeram uso da medicação antiparkinsoniana, associada à antidepressiva e, encontravam-se no estágio 3 HY, demonstraram escores mais elevados no IDV. Conclusão: a partir dos resultados obtidos foi observado, por meio de dois questionários distintos, a relação entre a QV e a voz em sujeitos com DP

O objetivo do presente estudo foi comparar os efeitos de dois tipos de programas de treinamento de equilíbrio, um baseado no Nintendo Wii Fit e o outro baseado nos exercícios tradicionais sem a utilização de videogame, no equilíbrio, funcionalidade e cognição de pacientes com doença de Parkinson. Trata-se de um ensaio clínico cego e randomizado realizado na Associação Brasil Parkinson e no Centro de Docência e Pesquisa dos Cursos de Fonoaudiologia, Fisioterapia e Terapia Ocupacional da Universidade de São Paulo. Participaram do estudo 32 pacientes com doença de Parkinson nos estágios 1 a 2,5 da escala Hoehn e Yahr. Os pacientes foram randomizados nos grupos controle e experimental, 16 em cada grupo. Ambos os grupos realizaram 14 sessões individuais de treinamento, duas vezes por semana, por sete semanas. Cada sessão foi composta por 30 minutos de exercícios globais, incluindo alongamento e fortalecimento musculares e mobilidade axial. Logo após, ambos os grupos realizaram mais 30 minutos de treinamento de equilíbrio: o treinamento do grupo controle foi realizado por meio de exercícios de equilíbrio sem a utilização de pistas externas, retroalimentação visual ou auditiva ou estimulação cognitiva associada; o grupo experimental realizou o treinamento de equilíbrio por meio de 10 jogos do Nintendo Wii Fit, os quais estimularam as funções motoras e cognitivas. As principais medidas do estudo foram (1) seção II da Escala Unificada da Doença de Parkinson, (UPDRS); (2) Escala de Equilíbrio de Berg (EEB); (3) Unipedal Stance Test (UST) e (4) Montreal Cognitive Assessment (MoCA). A análise estatística foi realizada por meio da ANOVA de medidas repetidas e o pós hoc teste de Tukey para a verificação de possíveis diferenças entre os grupos e avaliações realizadas antes, depois e após 60 dias do final do treinamento. Ambos os grupos apresentaram melhora na seção II da UPDRS, na EEB, no UST e na MoCA. Conclui-se que os pacientes com doença de Parkinson apresentaram melhora no equilíbrio e na cognição com efeitos positivos sobre a funcionalidade relacionada com as atividades de vida diária após 14 sessões de treinamento de equilíbrio sem vantagens adicionais para o treinamento em ambiente virtual / The objective of this work was to compare the effects of two balance training programs, one Nintendo Wii Fit-based and the other traditionally-based without the use of a gaming system, on the balance, functionality and cognition of patients with Parkinson´s disease. It was a prospective, single blinded, randomized clinical trial performed at Brazil Parkinson Association and Center of Research of the courses of Speech Therapy, Physical Therapy and Occupational Therapy of São Paulo University. 32 patients with Parkinson´s disease on stages 1 and 2,5 of Hoehn e Yahr participated of this work. Patients were randomized in control and experimental group, 16 each one. Both groups performed 14 training sessions, twice a week, for seven weeks. Each session was composed of a 30 minute-global-exercise series including stretching, muscle strengthen and axial mobility exercises. After this, both groups performed more 30 minutes of balance training: the control group performed balance exercises without external cues, visual or auditory feedbacks or cognitive stimulations; the experimental group performed the balance training with 10 Wii Fit games which stimulated motor and cognitive functions. The main outcome measures were: (1) Unified Parkinson´s Disease Rating Scale (UPDRS); (2) Berg Balance Scale (BBS); (3) Unipedal Stance Test (UST) and (4) Montreal Cognitive Assessment (MoCA). The statistical analysis was done by repeated measures ANOVA in order to assess the possible differences among the analyzed variables. Both groups showed improvement in the section II of UPDRS, BBS, UST and MoCA. Patients with Parkinson´s disease showed balance and cognitive improvement with positive repercussion on daily living activities after 14 sessions of balance training without additional advantages to the virtual training

A doença de Parkinson (DP) é a segunda doença neurodegenerativa mais comum com uma prevalência aproximada de 3% em pacientes com mais de 64 anos. A doença é esporádica, mas o parkinsonismo primário (PP) familiar, decorrente de defeitos genéticos específicos, tem sido encontrado em cerca de 10% dos casos diagnosticados como DP. Os objetivos deste trabalho são analisar o DNA de pacientes com PP acompanhados no ambulatório do Grupo de Estudo de Distúrbios do Movimento da Clínica Neurológica do Hospital das Clínicas da FMUSP que apresentam início precoce (< 40 anos) ou história familiar positiva com o intuito de rastrear mutações responsáveis pela doença e descrever as características clínicas desse grupo de pacientes e dos familiares acometidos. Entre Janeiro de 2004 a Janeiro de 2006 foram selecionados 53 probandos com PP, sendo que 29 eram esporádicos, 16 com história familiar sugestiva de herança autossômica dominante (AD) e 8 com história familiar sugestiva de herança de autossômica recessiva (AR). No total, 100 amostras de DNA foram coletadas, 70 de pacientes ou familiares com PP, 1 com parkinsonismo secundário ao uso de neuroléptico e o restante de familiares sem PP. Dos casos afetados, 45 eram do sexo masculino e 25 feminino, a idade média de início dos sintomas foi de 38,3 anos (10-72) e a média de idade no momento da investigação foi de 49,8 anos (22-72). Todos apresentaram instalação assimétrica do quadro, curso lento e progressivo e boa resposta ao tratamento com levodopa ou agonista dopaminérgico. Pacientes com padrão de herança AD foram testados para a mutação Gli2019Ser que é o defeito mais comum do gene LRRK2 (PARK8) sendo encontradas duas famílias afetadas. A análise mutacional dos genes PARK6 e PARK7 está em andamento. Todos os casos esporádicos e com padrão de transmissão AR foram testados para mutações do gene PARK2 e foram encontradas as seguintes mutações homozigóticas em 4 famílias: 255delA, deleção de exon 3-4, deleção do exon 2-3 e uma nova mutação IVS1+1G/T. Num paciente com parkinsonismo juvenil (idade de início dos sintomas <21 anos) foi encontrada uma nova mutação homozigótica no gene ATP13A2 (PARK9) no exon 15 que determina a substituição Gli504Arg na proteína codificada. Em grande parte dos casos estudados os achados genéticos e clínicos são similares aos descritos na literatura. Entretanto, encontramos novas mutações do gene PARK2 e PARK9 e no paciente com a mutação ATP13A2 os achados clínicos diferem em alguns aspectos da descrição clássica. / Parkinson disease (PD) is the second most common neurodegenerative disorder affecting approximately 3% of the population over age 64. Most cases of PD manifest in sporadic form, but familial primary parkinsonism (PP) due to specific genetical abnormalities has been found in about 10% of cases diagnosed as PD. The aims of this study were to analyze the DNA of PP patients seen at the Group for the Study of Movement Disorders of the Neurology Department of Hospital das Clinicas of the University of São Paulo who presented early onset of the disease (< 40 years of age) or positive family history, with the purpose of screening possible candidate mutations for the disease, and to describe the clinical features of this group of patients and affected members of their families. Between January 2004 and January 2006, 53 probands were selected of whom, 29 were sporadic cases, 16 had probable autosomical dominant (AD) pattern of inheritance, and 8 autosomical recessive (AR). In total 100 samples of DNA were collected, 70 from PP patients or affected relatives, one case with neuroleptic-induced parkinsonism, and the rest from not affected members. Forty five affected individuals were men and 25 women, the median age of the symptoms onset was 38.3 years (10-72), and the median age at the moment of the examination was 49.8 years (22-72). All patients had asymmetric installation of the disease, slow progression of the PP, and good response to levodopa or dopaminergic agonist therapy. Patients with AD inheritance were screened for Gly2019Ser mutation, which is the most common defect in PD due to LRRK2 gene, and two families carried this mutation. The screening of PARK6 and PARK7 is ongoing. All sporadic and AR inheritance cases were tested for mutation of (PARK2) and the following mutation were found in 4 families in homozygous state: 255delA, exon 3-4 deletion, exon 2-3 deletion, and a novel mutation IVS1+1G/T. In a juvenile parkinsonism proband (age of onset < 21 years) a novel missense homozygous mutation in ATP13A2 (PARK9) gene was found in exon 15 which resulted the Gly504Arg change in the encoded protein. In general the genetical and clinical findings of this series of patients are similar to those reported in the literature, although novel mutation in PARK2 and PARK9 were obtained. Some clinical features of the patient with ATP13A2 mutation differed from the classical descriptions.

OBJETIVO: A imagem molecular de transportadores de dopamina (DAT) oferecer uma informação diferencial na investigação de doenças neurodegenerativas, como a Doença de Parkinson, diante de uma sólida abordagem quantitativa. Porém, são diversos o número de diferentes métodos semiquantitativos aplicados na prática clínica, que nos quais podem produzir resultados distintos quando aplicados por diferentes avaliadores ou condições de avaliação da imagem de SPECT do corpo estriado. Logo, este estudo pode avaliar a acurácia, precisão e reprodutibilidade de diferentes métodos semiquantitativos de imagens de SPECT do corpo estriado. MATERIAIS E MÉTODOS: Foram realizadas 23 aquisições de SPECT utilizando um simulador antropomórfico estriatal preenchido com diferentes concentrações de atividade de 99mTc. A preparação deste simulador estriatal foi realizada a partir de concentrações de atividades nas cavidades de interesse (núcleo caudado, putâmen e corpo estriado) proporcionalmente maiores do que a da cavidade de referência (background). As imagens foram reconstruídas utilizando parâmetros ideais já protocolados. Cinco métodos baseados em ROIs, dedicados para a quantificação de SPECT do corpo estriado foram avaliados: ROIs desenhadas sobre as imagens de SPECT - (A) Manual, ROIs com dimensões padronizadas - (B) método Twobox e (C) método Threebox; e baseado em imagens estruturais (D) MRI e (E) CT. A acurácia de cada método aplicado foi avaliada através do coeficiente de correlação de concordância (CCC), sua precisão utilizando o coeficiente de Pearson e modelos regressão linear, assim como a reprodutibilidade pode ser investigada através de análises de variabilidade intra- e interobservadores. RESULTADOS: Tanto para as cavidades avaliadas de forma individual (Caudado e Putâmen), quanto para o corpo estriado como um todo, todos os métodos aplicados apresentaram um aumento no CCC dos índices quantificados diante de uma diminuição dos valores nominais de preenchimento. Os métodos D e E apresentaram os máximos valores de CCC na avaliação do núcleo caudado _ 0,89 baixo MRI CA CCC ? e _ 0,84 baixo CT CA CCC ? ) e putâmen ( _ 0,86 baixo MRI PU CCC ? e _ 0,82 baixo CT PU CCC ? ). Entretanto, na avaliação do corpo estriado, o método B apresentou a máxima acurácia dentre os cinco aplicados ( _ 0,95 baixo TWOBOX ST CCC ? ). A significante correlação entre os métodos foi evidenciada por um elevado coeficiente de correlação (r > 0.8). Na avaliação da reprodutibilidade intra e interobservadores uma grande variabilidade foi observada na aplicação do método A, principalmente quando aplicada na semiquantificação de baixas concentrações de atividade. Conclusão: Os cinco métodos semiquantitativos de SPECT do corpo estriado, demonstraram ser eficientes na realização de leituras proporcionais dos índices de BPI mesmo quando aplicados a imagens de diferentes concentrações de atividade. Porém, diante de investigações que necessitem de um processo de quantificação mais acurado e visando avaliar putâmen e núcleo caudado de forma isolada, os métodos estruturais (MRI e CT), demonstraram uma crescente eficiência em representar acurados parâmetros semiquantitativos diante da diminuição dos índices nominais de preenchimento. Na investigação de todo o corpo estriado e carente de qualquer informação estrutural, o método TwoBox passa a ser recomendado devido sua melhor performance diante todos os métodos avaliados. / AIM: The molecular image of dopamine transporters (DAT) gives differential information in research of neurodegenerative diseases, such as Parkinson\'s, when properly approached quantitatively. Yet, each method used in clinical routine may give, or not, different results when the quantifications are applied in images of several activity levels. Hence, this study assessed the accuracy, precision and reproducibility of striatum SPECT images semi-quantification methods, based in ROIs. METHODOLOGY: Twenty-three SPECT images were acquisitions of anthropomorphic striatal phantom filled with different activity concentrations of 99mTc. For each acquisition performed, the specific chambers (caudate and putamen chambers) to large chamber (simulating nonspecific background activity) was filled with solutions activity of different specific to nonspecific ratios (10, 8, 6, 4 and 2 to 1). The images were reconstructed by iterative algorithm, corrected to attenuation effects and the extracted values were analyzed by the specific binding ratio (SBR). Five semi-quantification methods for striatum SPECT, using ROIs was assessment: (A) draw freehand ROIs on SPECT image (manual); standard size ROIs: (B) TwoBox and (C) ThreeBox Methods and VOIs using structural images: (D) MRI and (E) CT. Accuracy of methods applied was assessed by concordance correlation coefficient (CCC) and precision by Pearson\'s coefficient and linear regression. RESUlTS: The SBR quantified both to individual specific chambers and striatal chamber analyzed to all methods applied resulted in a CCC increase with decrease of the nominal values used. For lower SBR values, the D and E methods evidenced the maximum values of CCC in assessment of caudate (CCCMRI_CA = 0.89 e CCCCT_CA = 0.84) and putamen (CCCMRI_PU = 0.86 e CCCCT_PU = 0.82). However, striatal assessments the B method highlights a maximum accuracy between all methods applied (CCCTWOBOX_ST = 0.95), for low values of SBR. A high Pearson\'s coefficient was found in the correlation between the all methods, report thereby a good precision between them (r > 0.8). The high ICC and variability values, showed a high reprodutibility intra- and interobserver for B, C and D methods, white the A and E methods presented a high variability between the raters. CONCLUSION: The five semi-quantification methods of striatum SPECT reported a high precision even when applied in images with activity solutions different. Therefore, to research much accurate and need to assessment just caudate or putamen individually the structural methods - MRI and CT - demonstrated progressive improvement in its quantification to reduction nominal fill index. To assessment striatal chamber and in the absence of structural information, the TwoBox method is advisable due to its excellent agreement with all nominal values when compared to the various semi-quantitative methods investigated. Keywords:

La maladie de Parkinson est la seconde pathologie neurodégénérative la plus fréquente après la maladie d’Alzheimer. Elle se manifeste par une mort progressive et continue des neurones dopaminergiques de la voie nigro-striée, accompagnée de troubles moteurs et non moteurs lourdement handicapants. La maladie de Parkinson touche près de 6,3 millions de personnes dans le monde, avec une répartition homogène sur l’ensemble de la planète. Il existe plusieurs thérapeutiques permettant de diminuer les symptômes des malades, dont les plus efficaces sont la dopa-thérapie et la stimulation cérébrale profonde. Toutefois, à ce jour, aucune stratégie visant à protéger les neurones dopaminergiques de la dégénérescence n’a démontré son efficacité chez l’humain. En parallèle, un nombre grandissant d’études montre le potentiel cytoprotecteur d’une illumination proche infrarouge. Récemment, plusieurs études ont démontré le potentiel neuroprotecteur de cette gamme de lumière sur des modèles rongeurs de la maladie de Parkinson. L’objectif du présent travail est de confirmer ce potentiel et d’optimiser son efficacité afin de préfigurer l’essai clinique à venir. Pour ce faire, avec les modèles MPTP souris et 6-OHDA unilatéral rat, nous avons étudié la faisabilité d’une illumination intracérébrale chronique, l’influence de la longueur d’onde, de la fenêtre temporelle de traitement (pré-, post-traitement), de la quantité globale d’énergie optique apportée (continu vs discontinu, nombre de flashs lumineux, énergie d’un seul flash), de la durée d’un flash et de la puissance optique appliquée sur l’efficacité thérapeutique. Nous démontrons ici la faisabilité d’une illumination intracérébrale chronique et son potentiel neuroprotecteur. Nous montrons par ailleurs que les longueurs d’onde 670 et 810 nm protègent toutes deux les neurones dopaminergiques dans nos modèles d’étude. Nous montrons une mise en place rapide des mécanismes de protection (< 20 min), et un maintien dans le temps pendant au moins 48 heures. De plus, nous observons qu’une illumination discontinue est préférable à une illumination continue. La quantité globale d’énergie optique appliquée semble ne pas avoir de rôle significatif sur l’efficacité du traitement. En revanche, il existe un seuil bas pour la puissance optique, qui semble régie par un effet « tout-ou-rien ». L’efficacité thérapeutique est également liée à la durée d’un flash lumineux, par « un effet en cloche », Tous ces résultats sont en adéquation avec la littérature scientifique qu’ils confirment et complètent. Couplés aux travaux sur primates non humains de mon équipe d’accueil, ils serviront de base de travail à la conception du futur essai clinique. / Parkinson’s disease is the second most common neurodegenerative disease, after Alzheimer disease. It is characterized by a slow, continuous death of dopaminergic neurons in the nigrostriatal pathway, followed by severe motor and non-motor symptoms. Parkinson’s disease affects 6.3 million peoples, with a homogeneous distribution worldwide.There are several symptomatic strategies applied in clinic, such as the dopa-therapy (gold standard) and the deep brain stimulation. However, theses therapeutical approaches are not neuroprotective. Indeed, to date, there is no strategy able to effectively slow or rescue the course of the disease. Alternatively, a growing number of studies show the cytoprotective potential of a near infrared illumination. Recently, several studies showed the neuroprotective potential of these wavelengths in rodent models of Parkinson disease.The aim of this work is to confirm and optimize the efficacy of a near infrared treatment in Parkinson’s disease, as the first step for the future clinical trial.We used the MPTP mice and the 6-OHDA unilateral rat models to assess the feasibility and the effectiveness of an intracerebral chronical illumination. We also measured the influence of the wavelength, the time window (pre-, post-treatment), the global optical energy delivered (continuous vs discontinuous, number of flashs, energy of one flash), the duration of one flash and the optical power on the therapeutical efficacy.We demonstrate here the feasibility of an intracerebral chronical illumination and its neuroprotective potential. We show that the 670 and 810 nm wavelengths both protect the dopaminergic cells in the rodent models, and produce a quick activation of the protective mechanisms (< 20 min). The neuroprotective effect stays effective at least 48 hours after the illumination. Moreover, we show that a discontinuous illumination seems better than a continuous one. The global optical energy delivered has no significant influence on the efficacy. In contrast, the optical power has an everything-or-nothing effect. The therapeutic efficacy is also flash duration dependent (bell effect).All these results confirm and complete the scientific literature. Together with the work on non-human primates from my team, these results will be useful to design the future clinical trial.

<p>The overall aim was to improve the knowledge and understanding of eating habits of older men with somatic diseases, and the men's perceptions about managing food-related habits, such as grocery shopping and cooking. A total of 67 men between 64 and 89 years of age were visited in their homes on two occasions with 1-2 weeks in between. The participants were diagnosed with one of the three diseases Parkinson’s disease, rheumatoid arthritis, or stroke. A food survey, with repeated 24-h recall, was used to assess food intake and meal patterns. Interviews with 18 participants were conducted with open-ended questions. The interviews were further analysed with a thematic framework approach.The findings showed that eating events were distributed over a 24-h period.Further, co-living men had a significantly larger number of eating events over the day (p=0.001). No differences in daily energy intake were observed between co-living and single-living men. Co-living men’s hot eating events were compared with those of single-living men more often cooked from fresh ingredients (p=0.001), including a greater mix of vegetables/roots (p=0.003).Thematic analysis revealed three different approaches to food-related activities(FRA), namely ‘Cooking as a pleasure’, describing joy in cooking; ‘Cooking as a need’, indicating no habits or skills in cooking; and ‘Food is served’, that is, being served meals by a partner. The men's approaches to FRA were affected in particular by gender-related roles, but also by changed life circumstances, activity limitations, personal interests, and a wish to maintain continuity and independence. Further adaptive strategies were used among the men in attempts to maintain continuity and independence in FRA. In conclusion, single-living older men, especially those with activity limitations, were identified as being a vulnerable group from a nutritional perspective. Further, health care efforts in promoting FRA should preferably be individualised with respect to the older man’s approach to these activities.</p>

The overall aim was to improve the knowledge and understanding of eating habits of older men with somatic diseases, and the men's perceptions about managing food-related habits, such as grocery shopping and cooking. A total of 67 men between 64 and 89 years of age were visited in their homes on two occasions with 1-2 weeks in between. The participants were diagnosed with one of the three diseases Parkinson’s disease, rheumatoid arthritis, or stroke. A food survey, with repeated 24-h recall, was used to assess food intake and meal patterns. Interviews with 18 participants were conducted with open-ended questions. The interviews were further analysed with a thematic framework approach.The findings showed that eating events were distributed over a 24-h period.Further, co-living men had a significantly larger number of eating events over the day (p=0.001). No differences in daily energy intake were observed between co-living and single-living men. Co-living men’s hot eating events were compared with those of single-living men more often cooked from fresh ingredients (p=0.001), including a greater mix of vegetables/roots (p=0.003).Thematic analysis revealed three different approaches to food-related activities(FRA), namely ‘Cooking as a pleasure’, describing joy in cooking; ‘Cooking as a need’, indicating no habits or skills in cooking; and ‘Food is served’, that is, being served meals by a partner. The men's approaches to FRA were affected in particular by gender-related roles, but also by changed life circumstances, activity limitations, personal interests, and a wish to maintain continuity and independence. Further adaptive strategies were used among the men in attempts to maintain continuity and independence in FRA. In conclusion, single-living older men, especially those with activity limitations, were identified as being a vulnerable group from a nutritional perspective. Further, health care efforts in promoting FRA should preferably be individualised with respect to the older man’s approach to these activities.

Parkinson disease (PD) is the most common movement disorder and the second most common neurodegenerative disease. PINK1, PTEN-induced kinase 1, functions as a serine/threonine kinase as well as a protector of mitochondrial function. Mutations in PINK1 gene result in either mitochondria dysfunction or disruption of kinase signaling pathways involved in the pathogenesis of PD. In this thesis, oxidative stress levels were examined in the brain of PINK1 knockout mice, and also how heme oxygenase-1 and biliverdin reductase are affected in brain of PINK1 knockout mice. In addition, posttranslational modifications are a way to control the behavior of proteins, so posttranslational modifications of the brain of PINK1 knockout mice, including both oxidative modification and phosphorylative modification, were examined.