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We recently described increased D- and L-serine concentrations in the striatum of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys, the post-mortem caudate-putamen of human Parkinson's disease (PD) brains and the cerebrospinal fluid (CSF) of de novo living PD patients. However, data regarding blood D- and L-serine levels in PD are scarce. Here, we investigated whether the serum profile of D- and L-serine, as well as the other glutamate N-methyl-D-aspartate ionotropic receptor (NMDAR)-related amino acids, (i) differs between PD patients and healthy controls (HC) and (ii) correlates with clinical-demographic features and levodopa equivalent daily dose (LEDD) in PD. Eighty-three consecutive PD patients and forty-one HC were enrolled. PD cohort underwent an extensive clinical characterization. Serum levels of D- and L-serine, L-glutamate, L-glutamine, L-aspartate, L-asparagine and glycine were determined using High Performance Liquid Chromatography. In age- and sex-adjusted analyses, no differences emerged in the serum levels of D-serine, L-serine and other NMDAR-related amino acids between PD and HC. However, we found that D-serine and D-/Total serine ratio positively correlated with age in PD but not in HC, and also with PD age at onset. Moreover, we found that higher LEDD correlated with lower levels of D-serine and the other excitatory amino acids. Following these results, the addition of LEDD as covariate in the analyses disclosed a selective significant increase of D-serine in PD compared to HC (Δ ≈ 38%). Overall, these findings suggest that serum D-serine and D-/Total serine may represent a valuable biochemical signature of PD.
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Doença de Parkinson , Humanos , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Serina/metabolismo , Dopamina/metabolismo , Levodopa/uso terapêutico , Aminoácidos , Ácido Glutâmico , EnvelhecimentoRESUMO
BACKGROUND: Cognitive dysfunction is a well-established manifestation of the post-COVID syndrome. Psychological vulnerability to stressors can modify disease trajectories, causing long-term risk for negative outcomes. Nonetheless, how premorbid risk factors and response to stressor affect neuropsychological changes is still incompletely understood. In this study, we explored the impact of psychosocial variables on cognitive functioning in a post-COVID sample. METHODS: All subjects were submitted to a comprehensive neuropsychological battery and an assessment of perceived loneliness, post-traumatic stress, and changes in anxiety and depression levels. A social vulnerability index was also calculated. The set of psycho-social variables was reduced to two Principal Component Analysis (PCA) components: distress and isolation. RESULTS: Forty-five percent of individuals showed cognitive impairments, with predominant memory and executive deficits. Post-traumatic stress disorder was clinically relevant in 44% of the sample. Social vulnerability scores of the sample were comparable to those of general population. The individual performance in learning and response initiation/suppression was directly related to distress component, encasing anxiety, stress, and depression measures. CONCLUSION: These findings suggest that psychosocial assessment of post-COVID patients can detect fragile individuals at risk of cognitive impairments. Dedicated psychological support services may play a useful role in the prevention of post-COVID cognitive dysfunction.
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COVID-19 , Disfunção Cognitiva , Humanos , COVID-19/complicações , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/etiologia , Cognição/fisiologia , Ansiedade/epidemiologia , Ansiedade/etiologia , Ansiedade/psicologia , Fatores de Risco , Depressão/epidemiologia , Depressão/etiologia , Depressão/psicologiaRESUMO
BACKGROUND: The prevalence of neurodegenerative diseases is expected to increase over the next years, therefore, new methods able to prevent and delay cognitive decline are needed. AIMS: To evaluate the effectiveness of a combined treatment protocol associating a computerized cognitive training (CoRe) with anodal transcranial direct current stimulation (tDCS). METHODS: In this randomized controlled trial, 33 patients in the early stage of cognitive impairment were assigned to the experimental group (CoRE + real tDCS) or control group (CoRE + sham tDCS). In each group, the intervention lasted 3 consecutive weeks (4 sessions/week). A neuropsychological assessment was administered at baseline (T0), post-intervention (T1) and 6-months later (T2). RESULTS: The CoRE + real tDCS group only improved in working memory and attention/processing speed at both T1 and T2. It reported a stable MMSE score at T2, while the CoRE + sham tDCS group worsened. Age, mood, and T0 MMSE score resulted to play a role in predicting treatment effects. CONCLUSION: Combined multi-domain interventions may contribute to preventing or delaying disease progression. TRIAL REGISTRATION: Trial registration number (ClinicalTrials.gov): NCT04118686.
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Transtornos Cognitivos , Disfunção Cognitiva , Estimulação Transcraniana por Corrente Contínua , Cognição , Disfunção Cognitiva/terapia , Método Duplo-Cego , Humanos , Testes NeuropsicológicosRESUMO
BACKGROUND: In Parkinson's disease (PD), physical activity may represent a possible non-pharmacological intervention not only for improving motor symptoms but also for modulating cognitive impairment. AIMS: To evaluate the efficacy of an intensive physical program on cognitive functions in mid-stage PD patients with mild cognitive impairment (PD-MCI) over a 6-month follow-up. METHODS: This is a 6-month randomized controlled follow-up study. 40 PD-MCI patients were randomized to receive physical therapy (PT) or no specific intervention beside drug treatment (CT). Cognitive and motor assessments were performed at baseline (T0), 4 weeks after baseline (T1) and 6 months after T0. In a previous study, we reported a significant improvement in global cognitive functioning and attention/working-memory at T1. Here, we evaluated the residual effect of the training intervention at 6 months on both cognitive and motor performances. RESULTS: Intra-group analysis showed that at T2 most of cognitive and motor performances remained stable in the PT when compared to T0, while a significant worsening was observed in the CT. Between-group comparison at T2 showed significantly better results in PT than CT as regards MoCA and motor scales. The percentage change of cognitive and motor performances between T1 and T2 confirmed the benefit of physical therapy on global cognitive functioning scores (MMSE and MoCA). CONCLUSIONS: In this follow-up extension of a longitudinal randomized controlled study, we demonstrated that physical therapy has a positive effect on cognitive functions, which extends beyond the duration of the treatment itself to, at least temporarily, reducing cognitive decline. TRIAL REGISTRATION: Trial registration number (ClinicalTrials.gov): NCT04012086 (9th July 2019).
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Disfunção Cognitiva , Doença de Parkinson , Cognição , Disfunção Cognitiva/terapia , Seguimentos , Humanos , Doença de Parkinson/terapia , Modalidades de FisioterapiaRESUMO
One thousand and 679 Alzheimer's Disease patients (early onset EO: 152 and late onset LO: 1527) were evaluated after 12, 36 and 60 months. At baseline EO patients have higher Mini Mental State examination (MMSE) and fewer comorbidities in respect to LO group. The MMSE score did not significantly differ after 12, 36 and 60 months; a more marked worsening in instrumental daily activities was observed after 36 months in the EO compared with the LO group. These data allow to conclude that EO patients may have a slight faster progression in the disease within the first 3 years after the diagnosis, but in a longer follow-up no differences exist in respect to LO group. The literature failed to identify specific factors capable to influence the disease progression in AD. Our data are in substantial agreement with the literature and seem to confirm the great heterogeneity of AD patients.
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Idade de Início , Doença de Alzheimer/fisiopatologia , Progressão da Doença , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
INTRODUCTION: The relationship between cognitive and functional impairment in Alzheimer Disease (AD) at the earliest stages of the disease is not well characterized. This study aimed at investigating such relationships along AD evolution by means of the Disability Assessment for Dementia (DAD). METHODS: Consecutive pairs of AD outpatients and their primary informal caregivers were enrolled. Patients were evaluated by means of the Mini Mental State Examination and neuropsychological tests. A clinician completed the Clinical Dementia Rating Scale to stage dementia severity and interviewed the caregivers to complete the Neuropsychiatric Inventory to assess behavioral disturbances and the DAD to evaluate patients' functional competence. RESULTS: A total of 158 dyads were enrolled; the Mini Mental State Examination score was used to stratify patients into 4 groups (>24; 20 to 23.9; 10 to 19.9; <10) that were compared. The statistical analysis revealed that all the cognitive domains were positively related to functional independence, but only logical and executive functions seemed to predict autonomy. An intergroup comparison did not show significant differences in the DAD subscales measuring initiation, planning and organization, and performance. The role of education emerged, confirming the relevance of cognitive reserve. DISCUSSION: As the field moves toward earlier intervention in preclinical AD, the detection of early functional changes may drive the definition of trials on prevention or intervention for dementia.
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Atividades Cotidianas/psicologia , Doença de Alzheimer/psicologia , Disfunção Cognitiva/psicologia , Participação Social/psicologia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico , Escalas de Graduação Psiquiátrica Breve , Cuidadores/psicologia , Disfunção Cognitiva/diagnóstico , Feminino , Humanos , Vida Independente , Estudos Longitudinais , MasculinoRESUMO
We report an update of our previous observations in Alzheimer's disease (AD) patients in the routine clinical practice considering in particular the interactions between age, concomitant pathologies, and treatment adherence. 2379 AD patients (M/F: 1058/1321, mean age: 74.1 ± 8.8) referred for a first visit to our center from September 2000 to April 2017. An increase of percentage of patients aged over 80 years along the years was confirmed (27% between September 2000 and December 2010, and 39% between January 2011 to April 2017). The patients over 80 years presented a Cumulative Illness Rating Scale (CIRS) significantly higher than patients under 80 years (p < 0.00001). Higher CIRS scores were associated with a lower treatment adherence (p < 0.0002) and greater cognitive impairment (p < 0.01). As people in advanced age with cognitive disorders will increase, our approach to dementing conditions has to change and fit to social and epidemiological modifications.
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Doença de Alzheimer/epidemiologia , Doença de Alzheimer/terapia , Disfunção Cognitiva/etiologia , Cooperação e Adesão ao Tratamento/estatística & dados numéricos , Distribuição por Idade , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Feminino , Humanos , Masculino , Testes de Estado Mental e Demência , Índice de Gravidade de DoençaRESUMO
Unlike in other chronic diseases, the Quality of Life (QoL) of patients affected by Alzheimer Disease (AD) has not been well established, primarily because of the difficulties stemming from the study of patients with cognitive disorders. Because no cure is currently available for AD, the optimization of QoL represents the best possible outcome attainable in all stages of disease, making QoL assessment mandatory. This study identified variables related to patients' QoL and examined the agreement between patients' and caregivers' QoL ratings. A total of 135 dyads (patient and principal caregiver) were enrolled in the study. Patients' QoL evaluations showed a negative relationship with depressive mood and a positive relationship with Activities of Daily Living (ADL), whereas caregivers' QoL ratings showed a negative relationship with patients' depressive mood and behavioral disturbances. Caregivers tended to underestimate patients' QoL compared with the patients' own self-evaluations, with patients' dependency in performing ADL and behavioral disorders as well as caregivers' burdens and depression being the main factors associated with the discrepancy in these evaluations. These findings suggest that the use of proxies as a substitute for the self-report of QoL data should be treated with caution, always accounting for the presence of potential bias.
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Atividades Cotidianas/psicologia , Doença de Alzheimer/psicologia , Cuidadores/psicologia , Satisfação do Paciente , Qualidade de Vida/psicologia , Inquéritos e Questionários , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Frailty is a common age-related clinical syndrome characterized by a decline in the function of multiple organ systems, increased vulnerability to stressors, and a huge socio-economic burden. Despite recent research efforts, the physiopathological mechanisms underlying frailty remain elusive and biomarkers able to predate its occurrence in the early stages are still lacking. Beyond its physical component, cognitive decline represents a critical domain of frailty associated with higher risk of adverse health outcomes. We measured by High-Performance Liquid Chromatography (HPLC) a pool of serum amino acids including L-glutamate, L-aspartate, glycine, and D-serine, as well as their precursors L-glutamine, L-asparagine, and L-serine in a cohort of elderly subjects encompassing the entire continuum from fitness to frailty. These amino acids are known to orchestrate excitatory and inhibitory neurotransmission, and in turn, to play a key role as intermediates of energy homeostasis and in liver, kidney, muscle, and immune system metabolism. To comprehensively assess frailty, we employed both the Edmonton Frail Scale (EFS), as a practical tool to capture the multidimensionality of frailty, and the frailty phenotype, as a measure of physical function. We found that D-serine and D-/Total serine ratio were independent predictors of EFS but not of physical frailty. Furthermore, higher levels of glycine, glycine/L-serine and D-/Total serine were associated with worse cognition and depressive symptoms in the frail group. These findings suggest that changes in peripheral glycine and serine enantiomers homeostasis may represent a novel biochemical correlate of frailty.
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Biomarcadores , Disfunção Cognitiva , Idoso Fragilizado , Glicina , Serina , Humanos , Masculino , Idoso , Serina/sangue , Feminino , Glicina/sangue , Biomarcadores/sangue , Disfunção Cognitiva/sangue , Idoso de 80 Anos ou mais , Fragilidade/sangueRESUMO
Background: Telerehabilitation has enabled a broader application of cognitive rehabilitation programs. We have recently developed HomeCoRe, a system for supporting cognitive intervention remotely with the assistance of a family member. The main goal of the present study was to determine usability and user experience of HomeCoRe in individuals at risk of dementia and in their family members. The association between subjects' technological skills and main outcome measures was evaluated as well. Methods: Fourteen individuals with subjective cognitive decline (SCD) or mild neurocognitive disorder (mNCD) were recruited to participate in this pilot study. All participants received a touch-screen laptop implemented with the HomeCoRe software. The intervention consisted of 18 sessions and included a patient-tailored adaptive protocol of cognitive exercises. Usability was assessed in terms of treatment adherence and participants' performance across sessions; user experience via self-reported questionnaires and a descriptive diary. Results: Usability and user experience were overall satisfactory and suggested usability, pleasantness, and high motivation while using HomeCoRe. Technological skills correlated only with the perceived ability to start and/or perform exercises autonomously. Discussion: These results, although preliminary, suggest that the usability and user experience of HomeCoRe are satisfactory and independent of technological skills. These findings encourage wider and more systematic use of HomeCoRe to overcome the current limitations of in-person cognitive rehabilitation programs and to reach more individuals at risk of dementia.
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BACKGROUND: Intracerebral hemorrhage and cognitive decline are typical clinical presentations of cerebral amyloid angiopathy (CAA). OBJECTIVE: To determine whether magnetic resonance imaging (MRI) features differ between CAA with hemorrhagic versus cognitive onset. METHODS: In this retrospective study, sixty-one patients with CAA were classified by onset presentation of the disease: hemorrhage (n = 31) or cognitive decline (n = 30). The two groups were compared for MRI markers of small vessel disease, namely cerebral microbleeds (CMBs), cortical superficial siderosis, white matter hyperintensities (WMHs), enlarged perivascular spaces, cortical microinfarcts, and visual rating scales for cortical atrophy. In the patients with cognitive onset, further exploratory analyses investigated MRI markers according to cerebrospinal fluid (CSF) and neuropsychological profiles. RESULTS: Patients with cognitive onset showed a higher prevalence of CMBs (p < 0.001), particularly in temporal (p = 0.015) and insular (p = 0.002) lobes, and a higher prevalence of WMHs (p = 0.012). Within the cognitive onset group, 12 out of 16 (75%) patients had an Alzheimer's disease (AD) CSF profile but did not differ in MRI markers from those without AD pathology. Patients with cognitive onset displayed a multidomain profile in 16 out of 23 (70%) cases; patients with this profile showed increased WMHs and CMBs in parietal lobes compared with the amnestic group (p = 0.002) and dysexecutive group (p = 0.032), respectively. CONCLUSION: Higher burdens of WMHs and CMBs, especially in temporal and insular lobes, are associated with the cognitive onset of CAA. MRI markers could help to shed light on the clinical heterogeneity of the CAA spectrum and its underlying mechanisms.
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Doença de Alzheimer , Angiopatia Amiloide Cerebral , Humanos , Estudos Retrospectivos , Angiopatia Amiloide Cerebral/complicações , Angiopatia Amiloide Cerebral/diagnóstico por imagem , Hemorragia Cerebral/etiologia , Hemorragia Cerebral/complicações , Neuroimagem , Imageamento por Ressonância Magnética/métodos , Doença de Alzheimer/complicações , Doença de Alzheimer/diagnóstico por imagem , CogniçãoRESUMO
Background: Heterozygous mutations in the GBA gene, encoding the lysosomal enzyme ß-glucocerebrosidase (GCase), are the most frequent genetic risk factor for Parkinson's disease (PD). GBA-related PD (GBA-PD) patients have higher risk of dementia and reduced survival than non-carriers. Preclinical studies and one open-label trial in humans demonstrated that the chaperone ambroxol (ABX) increases GCase levels and modulates α-synuclein levels in the blood and cerebrospinal fluid (CSF). Methods and analysis: In this multicentre, double-blind, placebo-controlled, phase II clinical trial, we randomise patients with GBA-PD in a 1:1 ratio to either oral ABX 1.2 g/day or placebo. The duration of treatment is 52 weeks. Each participant is assessed at baseline and weeks 12, 26, 38, 52 and 78. Changes in the Montreal Cognitive Assessment score and the frequency of mild cognitive impairment and dementia between baseline and weeks 52 are the primary outcome measures. Secondary outcome measures include changes in validated scales/questionnaires assessing motor and non-motor symptoms. Neuroimaging features and CSF neurodegeneration markers are used as surrogate markers of disease progression. GCase activity, ABX and α-synuclein levels are also analysed in blood and CSF. A repeated-measures analysis of variance will be used for elaborating results. The primary analysis will be by intention to treat. Ethics and dissemination: The study and protocols have been approved by the ethics committee of centres. The study is conducted according to good clinical practice and the Declaration of Helsinki. The trial findings will be published in peer-reviewed journals and presented at conferences. Trial registration numbers: NCT05287503, EudraCT 2021-004565-13.
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Background: Behavioral and psychological symptoms of dementia (BPSD) are a distressful condition. We aimed to investigate the BPSD distribution in subjects with cognitive impairment, and the potential correlations between BPSD and neurodegeneration in terms of cerebrospinal fluid (CSF) tau and brain atrophy. Methods: One-hundred patients with mild cognitive impairment (MCI) or dementia (Alzheimer's disease, AD; Lewy-body disease, LBD; frontotemporal dementia, FTD; vascular dementia, VD) underwent a complete diagnostic workup, including 3T-MRI and/or CT and CSF. Cortical atrophy was assessed with medial temporal atrophy (MTA), posterior atrophy (PA), and global cortical atrophy-frontal lobe (GCA-F) scales. BPSD were rated using the Neuropsychiatric Inventory (NPI), and BPSD clusters were defined according to the European Alzheimer Disease Consortium. Results: Delusions, hallucinations, and psychosis cluster were differently distributed among the diagnostic groups (p < 0.05, p < 0.001, and p < 0.05), with LBD patients showing higher scores for hallucinations (vs. MCI, p < 0.001, and AD, p < 0.05) and psychosis cluster (vs. MCI, p < 0.05). In primary dementias, we found a negative correlation between NPI total score and tau levels (p = 0.08), confirmed by beta regression (p < 0.01), while a positive non-significant relationship was observed in MCI. Higher GCA-F scores were associated with delusions and apathy (p < 0.05, on both hemispheres) and hallucinations (left: p < 0.01, right: p < 0.05). GCA-F scores were positively correlated with psychosis cluster (right: p < 0.05), and agitation/aggression (left: p < 0.05). Conversely, nighttime disturbances were positively correlated with both GCA-F and MTA scores (left: p < 0.01; right: p < 0.05). Conclusion: Our results suggest that psychotic symptoms are significantly more represented in LBD patients and that CSF tau and frontal atrophy are associated with the occurrence and severity of BPSD in clinical practice. Longitudinal studies are however required to ascertain their actual predictive value.
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STUDY OBJECTIVES: To evaluate neurophysiological alterations of visual function in idiopathic REM sleep Behavior Disorder (iRBD) both as markers and predictors of neurodegenerative disorders. METHODS: In a longitudinal follow-up study of 46 consecutive iRBD patients (follow-up duration 8.4 ± 3.4 years), the baseline parameters in luminance-contrast pattern (VEPp), red-green color (VEPc) and motion-onset (VEPm) Visual Evoked Potentials in iRBD were compared to early (ePD) and advanced (aPD) Parkinson's Disease subjects. Parameters of latency and amplitude of iRBD converters to neurodegenerative disease were compared with those of the non-converters. RESULTS: The VEP P100 mean latency values for both eyes and for both stimulation checks (30' and 15') were significantly longer in all the three groups of patients as compared to controls; moreover latencies were longer in aPD than in the iRBD group who did not differ from the ePD group. The same held true when we analyzed the number of abnormal subjects belonging to each diagnostic group with a higher number of abnormal subjects in the aPD group compared to both the ePD and in iRBD groups. Chromatic and motion potentials were not different from controls and did not differ in the 3 diagnostic groups. The iRBD subjects who converted to a neurodegenerative disorder showed longer P100 latencies and a higher occurrence of VEPp abnormalities than those who did not convert. Again chromatic and motion VEPs were not different depending on conversion. CONCLUSIONS: In iRBD patients the detection of an abnormal VEPp should be considered as a red flag for possible synnucleinopathy, eventually contributing in stratifying the risk of phenoconversion.
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Doenças Neurodegenerativas , Doença de Parkinson , Transtorno do Comportamento do Sono REM , Potenciais Evocados Visuais , Seguimentos , HumanosRESUMO
It is shown that the circadian system is affected in patients with Alzheimer's disease (AD) even at an early stage of the disease and that such dysfunction may be detrimental to sleep, mood, and cognitive functioning. Light is a strong central modulator of the circadian rhythms and is potentially beneficial to mood and cognitive functioning via a direct effect or indirectly via its modulating effects on circadian rhythms. This study focuses on tracking the effect of light therapy on sleep quality, mood, and cognition in AD of mild/moderate severity. We performed a single-blind randomized controlled trial to investigate the effects of a light therapy treatment tailored to the individual circadian phase as measured by dim light melatonin onset (DLMO). Such a treatment induced an objective circadian phase shift consistent with the melatonin phase response curve to light exposure, led to a shortening of the phase angle DLMO-falling asleep time, and was associated with an improvement in subjective sleep quality and cognitive performance.
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Doença de Alzheimer , Demência , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/terapia , Demência/diagnóstico , Demência/epidemiologia , Demência/terapia , Diagnóstico Precoce , Humanos , Itália/epidemiologia , Centros de Cuidados de Saúde Secundários/estatística & dados numéricos , Índice de Gravidade de DoençaRESUMO
OBJECTIVE: In this prospective, controlled, monocentric study, we described the clinical and neuroimaging 12-month follow-up of two parallel cohorts of subjects with idiopathic normal pressure hydrocephalus (iNPH), who did or did not undergo lumboperitoneal shunt (LPS). METHODS: We recruited 78 iNPH patients. At baseline, subjects underwent clinical and neuropsychological assessments, 3 T magnetic resonance imaging (MRI), and tap test. After baseline, 44 patients (LPS group) opted for LPS implantation, whereas 34 subjects (control group) declined surgery. Both cohorts were then followed up for 12 months through scheduled clinical and neuropsychological evaluations every 6 months. 3 T MRI was repeated at 12-month follow-up. RESULTS: Gait, balance, and urinary continence improved in the LPS group, without significant influence on cognitive functions. Conversely, gait and urinary continence worsened in the control group. No preoperative MRI parameter was significant outcome predictor after LPS. Of relevance, in responders to LPS, we found postoperative reduction of periventricular white matter (PWM) hyperintensities, which were instead increased in the control group. CONCLUSIONS: LPS is safe and effective in iNPH. An early surgical treatment is desirable to prevent clinical worsening. Post-surgery decrease of PWM hyperintensities may be a useful MRI marker surrogate for clinical effectiveness of LPS.
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Hidrocefalia de Pressão Normal , Humanos , Hidrocefalia de Pressão Normal/diagnóstico por imagem , Hidrocefalia de Pressão Normal/cirurgia , Imageamento por Ressonância Magnética , Neuroimagem , Testes Neuropsicológicos , Estudos ProspectivosRESUMO
BACKGROUND: Sleep disorders and cognitive impairment are frequently reported in Parkinson's disease (PD) as non-motor disabling symptoms. While it is known that REM sleep Behaviour Disorder (RBD) in PD is associated with motor and cognitive decline, little is known about the neurobiological significance of NREM sleep arousal-related disorders. OBJECTIVES: to evaluate the cognitive and clinical correlates of arousal-related disorders in PD. METHODS: Clinical data and video-polysomnography were analysed from one hundred-seventy consecutive subjects with PD. Based on the neuropsychological assessment, the subjects were divided into three groups: no cognitive impairment (PD; n = 58), mild cognitive impairment (PD-MCI; n = 58) and overt dementia (PDD; n = 54). RESULTS: Arousal-related disorders by history were reported in 32.9% of the subjects: 10.3% PD, 31.6% PD-MCI and 59.3% PDD (p = 0.001). Video-PSG captured arousal-related disorders in 1.7% PD, 21.2% MCI-PD and 35.6% PDD (p = 0.001). Arousal-related disorders and RBD were recorded in the same night in 7.7% PD, 9.8% MCI-PD and 15.6% PDD (p = 0.04). Patients with arousal-related disorders captured at V-PSG have a longer disease duration (p = 0.003), higher UPDRS score (p = 0.039), longer duration of treatment with levodopa (p = 0.017) and dopamine agonists (p = 0.018), worse H&Y staging (p = 0.001), lower MMSE score (p = 0.019) and more frequently hallucinations (p = 0.004). In multivariate analysis, cognitive impairment significantly increases the risk of arousal-related disorders (OR 3.387-95% CI 1.395-8.220, p = 0.007). CONCLUSION: Arousal-related disorders appear to be a marker of cognitive decline in PD. Recognizing arousal-related disorders should make clinicians aware of a possible cognitive decline in PD and eventually modify the therapeutic approach.