Brain metabolites are associated with sleep architecture and cognitive functioning in older adults.

Sleep deficits are a possible risk factor for development of cognitive decline and dementia in older age. Research suggests that neuroinflammation may be a link between the two. This observational, cross-sectional study evaluated relationships between sleep architecture, neuroinflammation and cognitive functioning in healthy older adults. Twenty-two adults aged ≥60 years underwent whole-brain magnetic resonance spectroscopic imaging (in vivo method of visualizing increased brain temperatures as a proxy for neuroinflammation), supervised laboratory-based polysomnography, and comprehensive neurocognitive testing. Multiple regressions were used to assess relationships between magnetic resonance spectroscopic imaging-derived brain temperature and metabolites related to inflammation (choline; myo-inositol; N-acetylaspartate), sleep efficiency, time and % N3 sleep and cognitive performance. Choline, myo-inositol and N-acetylaspartate were associated with sleep efficiency and cognitive performance. Higher choline and myo-inositol in the bilateral frontal lobes were associated with slower processing speed and lower sleep efficiency. Higher choline and myo-inositol in bilateral frontoparietal regions were associated with better cognitive performance. Higher N-acetylaspartate around the temporoparietal junction and adjacent white matter was associated with better visuospatial function. Brain temperature was not related to cognitive or sleep outcomes. Our findings are consistent with the limited literature regarding neuroinflammation and its relationships with sleep and cognition in older age, which has implicated ageing microglia and astrocytes in circadian dysregulation, impaired glymphatic clearance and increased blood-brain barrier integrity, with downstream effects of neurodegeneration and cognitive decline. Inflammatory processes remain difficult to measure in the clinical setting, but magnetic resonance spectroscopic imaging may serve as a marker of the relationship between neuroinflammation, sleep and cognitive decline in older adults.

Diffusion Tensor Imaging-Along the Perivascular-Space Index Is Associated with Disease Progression in Parkinson's Disease.

BACKGROUND: The glymphatic clearance pathway is a waste clearance system that allows for removal of soluble proteins such as amyloid ß (Aß) from the brain. Higher Aß levels are associated with cognitive dysfunction in Parkinson's disease (PD). Diffusion tensor imaging-along the perivascular space (DTI-ALPS) is an imaging measure proposed to indirectly measure glymphatic function. OBJECTIVES: Evaluate differences in DTI-ALPS-index between PD and healthy controls (HC) and characterize relationships between this proposed measure of glymphatic clearance, cognition, and disease severity in PD. METHODS: PD (n = 32) and HC (n = 23) participants underwent brain imaging to assess DTI-ALPS. PD participants were classified as PD-normal cognition (PD-NC; n = 20) or PD-mild cognitive impairment (PD-MCI; n = 12) based on a Level II comprehensive cognitive assessment. A subgroup of PD participants (n = 21) returned for annual assessments for up to 4 years after baseline. Longitudinal outcomes included changes in performance on the comprehensive cognitive assessment and changes in the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS). RESULTS: PD participants had lower DTI-ALPS-index compared to HC. PD participants classified as PD-MCI had significantly lower DTI-ALPS-index compared to PD-NC. Lower DTI-ALPS-index at baseline was associated with longitudinal cognitive decline and worse longitudinal disease severity. CONCLUSIONS: Glymphatic clearance, as measured with DTI-ALPS, has potential to serve as a marker of longitudinal disease progression. Interventions targeting glymphatic function should be explored for potential to slow cognitive decline in PD. © 2024 International Parkinson and Movement Disorder Society.

Cognitive Symptoms in Cross-Sectional Parkinson Disease Cohort Evaluated by Human-in-the-Loop Machine Learning and Natural Language Processing.

Background and Objectives: Cognitive impairment is experienced by up to 80% of people with Parkinson disease (PD). Little is known regarding the subjective experience and frequency of bothersome cognitive problems across the range of disease duration as expressed directly in patients' own words. We describe the types and frequency of bothersome cognitive symptoms reported verbatim by patients with PD. Methods: Through the online Fox Insight study and the Parkinson Disease Patient Report of Problems, we asked patients with PD to self-report by keyboard entry up to five most bothersome problems and how these problems affect their functioning. Human-in-the-loop curation, natural language processing, and machine learning were used to categorize responses into 8 cognitive symptoms: memory, concentration/attention, cognitive slowing, language/word finding, mental alertness/awareness, visuospatial abilities, executive abilities/working memory, and cognitive impairment not otherwise specified. Associations between cognitive symptoms and demographic and disease-related variables were examined in our cross-sectional cohort using multivariate logistic regression. Results: Among 25,192 participants (55% men) of median age 67 years and 3 years since diagnosis (YSD), 8,001 (32%) reported a cognitive symptom at baseline. The 3 most frequently reported symptoms were memory (13%), language/word finding (12%), and concentration/attention (9%). Depression was significantly associated with bothersome cognitive problems in all domains except visuospatial abilities. Predictors of reporting any cognitive symptom in PD were depression (adjusted OR 1.5), increasing MDS-UPDRS Part II score (OR 1.4 per 10-point increment), higher education (OR 1.2 per year), and YSD 1, 2, 6-7, and 8-9 vs 0 YSD. Among individuals with at least one cognitive symptom, posterior cortical-related cognitive symptoms (i.e., visuospatial, memory, and language) were reported by 17% (n = 4325), frontostriatal-related symptoms (i.e., executive abilities, concentration/attention) by 7% (n = 1,827), and both by 14.2% (n = 1,020). Odds of reporting posterior cortical symptoms vs frontostriatal symptoms increased with age and MDS-UPDRS part II score, but not depression. Discussion: Nearly one-third of participants with PD, even early in the disease course, report cognitive symptoms as among their most bothersome problems. Online verbatim reporting analyzed by human-in-the-loop curation, natural language processing, and machine learning is feasible on a large scale and allows a detailed examination of the nature and distribution of cognitive symptoms in PD.

Effects of exercise on sleep in patients with epilepsy: A systematic review.

Exercise interventions in epilepsy have been shown to improve seizure frequency, physical capacity, quality of life, mood, and cognitive functioning. However, the effectiveness of exercise in improving sleep in epilepsy is less clear. The purpose of this report is to identify the published literature regarding exercise interventions in people with epilepsy to determine 1) what proportion of published clinical trials assess sleep as an outcome, and 2) what benefits of exercise interventions on sleep have been observed. We searched the PubMed, PsycINFO, and SCOPUS electronic databases using the search terms "epilepsy AND [exercise OR physical activity]" and identified 23 articles reporting on 18 unique clinical trials. Nine studies were conducted in adults, five in children, and four in adults and children with active seizures, controlled seizures, or both. Exercise modalities included aerobic exercise, strength training, walking, and yoga, among others, and some also included educational and motivational components. Exercise effects on sleep were tested in four studies, two of which only included indirect measures of sleep- and rest-related fatigue, with mixed results. Of the two reports assessing sleep directly, one reported marginal non-significant improvements in subjective sleep quality and no improvements in objective sleep quality in children after twelve weeks of walking, and the other reported no benefits in subjective sleep quality after twelve weeks of combined aerobic, strength, and flexibility training in adults. Given the health benefits of sleep and detrimental effects of sleep deprivation in epilepsy, epilepsy researchers need to assess the effects of exercise interventions on sleep.

Relationship between sleep, physical fitness, brain microstructure, and cognition in healthy older adults: A pilot study.

BACKGROUND: There is a critical need for neuroimaging markers of brain integrity to monitor effects of modifiable lifestyle factors on brain health. This observational, cross-sectional study assessed relationships between brain microstructure and sleep, physical fitness, and cognition in healthy older adults. METHODS: Twenty-three adults aged 60 and older underwent whole-brain multi-shell diffusion imaging, comprehensive cognitive testing, polysomnography, and exercise testing. Neurite Orientation Dispersion and Density Imaging (NODDI) was used to quantify neurite density (NDI) and orientation dispersion (ODI). Diffusion tensor imaging (DTI) was used to quantify axial diffusivity (AxD), fractional anisotropy (FA), mean diffusivity (MD), and radial diffusivity (RD). Relationships between sleep efficiency (SE), time and percent in N3 sleep, cognitive function, physical fitness (VO2 peak) and the diffusion metrics in regions of interest and the whole brain were evaluated. RESULTS: Higher NDI in bilateral white and gray matter was associated with better executive functioning. NDI in the right anterior cingulate and adjacent white matter was positively associated with language skills. Higher NDI in the left posterior corona radiata was associated with faster processing speed. Physical fitness was positively associated with NDI in the left precentral gyrus and corticospinal tract. N3 % was positively associated with NDI in the left caudate and right pre- and postcentral gyri. Higher ODI in the left putamen and adjacent white matter was associated with better executive function. CONCLUSION: NDI and ODI derived from NODDI are potential neuroimaging markers for associations between brain microstructure and modifiable risk factors in aging. If these associations are observable in clinical samples, NODDI could be incorporated into clinical trials assessing the effects of modifiable risk factors on brain integrity in aging and neurodegenerative diseases.

In Their Own Words: Fears Expressed by People with Parkinson's Disease in an Online Symptom Database.

Parkinson's disease (PD) carries substantial psychosocial burden. Using a database of responses by people with PD reporting up to five "most bothersome problems," we identified 225 fear-based verbatims, which were organized using the framework method into 26 categories. Commonly-reported fears included uncertainty of progression (n = 60, 26.7%), fear of future cognitive impairment (n = 24, 10.7%) and fear of becoming a burden on others (n = 23, 10.2%). Fears in PD are wide-ranging and can constitute the most bothersome aspect of the condition. These data can be used to design interventions to lessen the psychosocial burden of PD.

Association between Subjective Cognitive Complaints and Incident Functional Impairment in Parkinson's Disease.

BACKGROUND: Early identification of subjective cognitive complaints (SCC) in Parkinson's disease (PD) may improve patient care if it predicts cognition-related functional impairment (CFI). OBJECTIVES: The aim was to determine the cross-sectional and longitudinal association between SCC and CFI in PD. METHODS: Data were obtained from Fox Insight, an online longitudinal study that collects PD patient-reported outcomes. Participants completed a PD Patient Report of Problems that asked participants for their five most bothersome disease problems. SCCs were placed into eight categories through human-in-the-loop curation and classification. CFI had a Penn Parkinson's Daily Activities Questionnaire (PDAQ-15) score ≤49. Cox proportional hazards models and Kaplan-Meier survival analyses determined if baseline SCC was associated with incident CFI. RESULTS: The PD-PROP cohort (N = 21,160) was 55.8% male, mean age was 65.9 years, and PD duration was 4.8 years. At baseline, 31.9% (N = 6750) of participants reported one or more SCCs among their five most bothersome problems, including memory (13.2%), language/word finding (12.5%), and concentration/attention (9.6%). CFI occurred in 34.7% (N = 7332) of participants. At baseline, SCC was associated with CFI (P-value <0.001). SCC at baseline was associated with incident CFI (hazard ratio [HR] = 1.58 [95% confidence interval: 1.45, 1.72], P-value <0.001), as did cognitive impairment not otherwise specified (HR = 2.31), executive abilities (HR = 1.97), memory (HR = 1.85), and cognitive slowing (HR = 1.77) (P-values <0.001). Kaplan-Meier curves showed that by year 3 an estimated 45% of participants with any SCC at baseline developed new-onset CFI. CONCLUSIONS: Self-reported bothersome cognitive complaints are associated with new-onset CFI in PD. Remote electronic assessment can facilitate widespread use of patient self-report at population scale. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Heart rate variability during sleep in synucleinopathies: a review.

Synucleinopathies are a group of neurodegenerative diseases characterized by abnormal accumulations of insoluble alpha-synuclein in neurons or glial cells. These consist of Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Moreover, idiopathic REM sleep behavior disorder (iRBD) is often the first manifestation of synucleinopathies, demonstrating a pathophysiological continuum. While these disorders vary in prevalence, symptom patterns, and severity, they can all include autonomic nervous system (ANS) dysfunction, which significantly reduces quality of life and worsens prognosis. Consequently, identifying abnormalities of the ANS can provide opportunities for improving quality of life through symptomatic treatments that are tailored to the individual's symptoms. An exciting development is using heart rate variability (HRV) as a non-invasive research tool for analyzing how the ANS regulates physiological processes. HRV during sleep, however, may provide a more accurate and reliable measure of ANS activity than during wakefulness, as during awake time, ANS activity is influenced by a variety of factors, including physical activity, stress, and emotions, which may mask or confound the underlying patterns of ANS activity. This review aims to provide an overview of the current knowledge regarding sleep-related HRV in synucleinopathies and to discuss contributing mechanisms. Evidence suggests that iRBD, PD, and MSA are associated with nocturnal ANS dysfunction. Further, comparative studies indicate that the presence of RBD could exacerbate this abnormality. In contrast, no studies have been conducted in patients with DLB. Overall, this review provides new insight into the complex interplay between the ANS and synucleinopathies and underscores the need for further research in this area to develop effective therapies to improve sleep and overall quality of life in patients with synucleinopathies.