Gene dosage compensation of rRNA transcript levels in Arabidopsis thaliana lines with reduced ribosomal gene copy number.

The 45S rRNA genes (rDNA) are among the largest repetitive elements in eukaryotic genomes. rDNA consists of tandem arrays of rRNA genes, many of which are transcriptionally silenced. Silent rDNA repeats may act as 'back-up' copies for ribosome biogenesis and have nuclear organization roles. Through Cas9-mediated genome editing in the Arabidopsis thaliana female gametophyte, we reduced 45S rDNA copy number (CN) to a plateau of ∼10%. Two independent lines had rDNA CNs reduced by up to 90% at the T7 generation, named low copy number (LCN) lines. Despite drastic reduction of rDNA copies, rRNA transcriptional rates, and steady-state levels remained the same as wild-type plants. Gene dosage compensation of rRNA transcript levels was associated with reduction of silencing histone marks at rDNA loci and altered Nucleolar Organiser Region 2 organization. Although overall genome integrity of LCN lines appears unaffected, a chromosome segmental duplication occurred in one of the lines. Transcriptome analysis of LCN seedlings identified several shared dysregulated genes and pathways in both independent lines. Cas9 genome editing of rRNA repeats to generate LCN lines provides a powerful technique to elucidate rDNA dosage compensation mechanisms and impacts of low rDNA CN on genome stability, development, and cellular processes.

Perception of cognitive change by individuals with Parkinson's disease or essential tremor seeking deep brain stimulation: Utility of the cognitive change index.

OBJECTIVE: The Cognitive Change Index (CCI-20) is a validated questionnaire that assesses subjective cognitive complaints (SCCs) across memory, language, and executive domains. We aimed to: (a) examine the internal consistency and construct validity of the CCI-20 in patients with movement disorders and (b) learn how the CCI-20 corresponds to objective neuropsychological and mood performance in individuals with Parkinson's disease (PD) or essential tremor (ET) seeking deep brain stimulation (DBS). METHODS: 216 participants (N = 149 PD; N = 67 ET) underwent neuropsychological evaluation and received the CCI-20. The proposed domains of the CCI-20 were examined via confirmatory (CFA) and exploratory (EFA) factor analyses. Hierarchical regressions were used to assess the relationship among subjective cognitive complaints, neuropsychological performance and mood symptoms. RESULTS: PD and ET groups were similar across neuropsychological, mood, and CCI-20 scores and were combined into one group who was well educated (m = 15.01 ± 2.92), in their mid-60's (m = 67.72 ± 9.33), predominantly male (63%), and non-Hispanic White (93.6%). Previously proposed 3-domain CCI-20 model failed to achieve adequate fit. Subsequent EFA revealed two CCI-20 factors: memory and non-memory (p < 0.001; CFI = 0.924). Regressions indicated apathy and depressive symptoms were associated with greater memory and total cognitive complaints, while poor executive function and anxiety were associated with more non-memory complaints. CONCLUSION: Two distinct dimensions were identified in the CCI-20: memory and non-memory complaints. Non-memory complaints were indicative of worse executive function, consistent with PD and ET cognitive profiles. Mood significantly contributed to all CCI-20 dimensions. Future studies should explore the utility of SCCs in predicting cognitive decline in these populations.

The Relationship Between Autonomic Dysfunction and Mood Symptoms in De Novo Parkinson's Disease Patients Over Time.

BACKGROUND: Autonomic dysfunction is prevalent in Parkinson's disease (PD) and can worsen quality of life. We examined: (a) whether specific autonomic symptoms were more strongly associated with anxiety or depression in PD and (b) whether overall autonomic dysfunction predicted mood trajectories over a 5-year period. METHODS: Newly diagnosed individuals with PD (N = 414) from the Parkinson's Progression Markers Initiative completed self-report measures of depression, anxiety, and autonomic symptoms annually. Cross-sectional linear regressions examined relationships between specific autonomic subdomains (gastrointestinal, cardiovascular, thermoregulatory, etc.) and mood. Multilevel modeling examined longitudinal relationships with total autonomic load. RESULTS: Gastrointestinal symptoms were associated with both higher anxiety (b = 1.04, 95% CI [.55, 1.53], P < .001) and depression (b = .24, 95% CI [.11, .37], P = .012), as were thermoregulatory symptoms (anxiety: b = 1.06, 95% CI [.46, 1.65], P = .004; depression: b = .25, 95% CI [.09, .42], P = .013), while cardiovascular (b = .36, 95% CI [.10, .62], P = .012) and urinary symptoms (b = .10, 95% CI [.01, .20], P = .037) were associated only with depression. Longitudinally, higher total autonomic load was associated with increases in both depression (b = .01, 95% CI [.00, .02], P = .015) and anxiety (b = .04, 95% CI [.01, .06], P < .001) over time, as well as occasion-to-occasion fluctuations (depression: b = .08, 95% CI [.05, .10], P < .001; anxiety: b = .24, 95% CI [.15, .32], P < .001). CONCLUSION: Findings suggest autonomic dysfunction, particularly gastrointestinal and thermoregulatory symptoms, may be an indicator for elevated anxiety/depression and a potential treatment target early on in PD.

Greater Apathy Associated With Selective Serotonin Reuptake Inhibitor Use in Parkinson's Disease.

OBJECTIVE: Apathy, a motivational disorder, is common in Parkinson's disease (PD) and often misdiagnosed as depression. Use of selective serotonin reuptake inhibitors (SSRIs) has been associated with increased apathy in adolescents and adults with depression. Based on observations that serotonin may downregulate dopaminergic systems, we examined the relationship between apathy and SSRI use in individuals with PD. METHODS: Medications, mood/motivation scales, and clinical data were collected from a convenience sample of 400 individuals with PD. Depression and apathy were measured using the Beck Depression Inventory-II (BDI-Il) and the Apathy Scale (AS). Antidepressant medications were grouped by mechanism type. RESULTS: Of the 400 PD patients, 26% were on SSRIs. On standard mood/motivation scales, 38% of the sample exceeded clinical cut-offs for apathy and 28% for depression. Results of hierarchical regression analyses revealed that SSRIs were the only antidepressant that were significantly associated with higher apathy scores (ß = .1, P = .02). Less education (ß = -.1, P = .01) worse cognition (ß = -.1, P = .01), and greater depressive symptoms (ß = .5, P < .001) were also significant predictors of apathy. CONCLUSION: These findings suggest that use of SSRIs, but not other antidepressants, is associated with greater apathy in PD. Given the interactive relationship between serotonin and dopamine, the current findings highlight the importance of considering apathy when determining which antidepressants to prescribe to individuals with PD. Similarly, switching a SSRI for an alternative antidepressant in individuals with PD who are apathetic may be a potential treatment for apathy that needs further study.

Laterality of motor symptom onset and facial expressivity in Parkinson disease using face digitization.

The onset of motor symptoms in Parkinson disease (PD) is typically unilateral. Previous work has suggested that laterality of motor symptoms may also influence non-motor symptoms including cognition and emotion perception. In line with hemispheric differences in emotion processing, we tested whether left side/right brain motor onset was associated with worse expression of facial affect when compared to right side/left brain motor onset. We evaluated movement changes associated with facial affect in 30 patients with idiopathic PD (15 left-sided motor onset, 15 right-sided motor onset) and 20 healthy controls. Participants were videotaped while posing three facial expressions: fear, anger, and happiness. Expressions were digitized and analyzed using software that extracted three variables: two measures of dynamic movement change (total entropy and entropy percent change) and a measure of time to initiate facial expression (latency). The groups did not differ in overall amount of movement change or percentchange. However, left-sided onset PD patients were significantly slower in initiating anger and happiness facial expressions than were right-sided onset PD patients and controls. Our results indicated PD patients with left-sided symptom onset had greater latency in initiating two of three facial expressions, which may reflect laterality effects in intentional behaviour.

Extensive Variations in Diurnal Growth Patterns and Metabolism Among Ulva spp. Strains.

Green macroalgae of the genus Ulva play a key role in coastal ecosystems and are of increasing commercial importance. However, physiological differences between strains and species have yet to be described in detail. Furthermore, the strains of Ulva used in aquaculture usually originate from opportunistic collection in the wild without prior selection of best performing strains. Hence, efforts are required to detect the potential variability in growth and metabolic accumulation between Ulva strains and ultimately select the best performing strains under given environmental conditions. Here, the growth, physiological, and metabolic characteristics of 49 laminar Ulva spp. strains were investigated using a custom-made high-throughput phenotyping platform, enzymatic assays, and gas chromatography-mass spectrometry. We found large natural variation for a wide range of growth and metabolic characteristics, with growth rates varying from 0.09 to 0.37 mg.mg-1d-1 among strains. Ulva spp. possess a unique diurnal growth pattern and primary metabolism compared with land plants, with higher growth rates during the night than during the light period. Starch and sucrose only contributed on average 35% of the carbon required to sustain Ulva's night growth. Nitrates accumulated during the night in Ulva tissues, and nitrate accumulation and consumption was positively correlated with growth. In addition, we identified six amino acids as possible biomarkers for high growth in Ulva The large variability in growth and metabolite accumulation recorded among morphologically similar Ulva strains justifies future efforts in strain selection for increasing biomass, metabolite yields, and nutrient removal in the growing aquaculture industry.

Does the Geriatric Depression Scale measure depression in Parkinson's disease?

The Geriatric Depression Scale (GDS) is recommended for screening depression in individuals with Parkinson's disease (PD). Empirical evidence, however, is limited regarding its validity and factor structure in PD. Thus, the current study sought to evaluate the convergent and divergent validity of the GDS, as well as the structure and validity of the derived factors. METHOD: Nondemented individuals with PD (n = 158) completed the GDS-30, and items were subjected to a principle component analysis. Geriatric Depression Scale total and factor scores were correlated with depression items from the Movement Disorder Society Unified Parkinson's disease Rating Scale (MDS-UPDRSd) and Hamilton Rating Scale for Depression (HAMDd), as well as with the Apathy Scale (AS), State-Trait Anxiety Inventory (STAI), Modified Fatigue Impact Scale (MFIS), Parkinson's disease Sleep Scale, and a Subjective Cognitive Function composite score. RESULTS: The GDS total score was strongly correlated with divergent neuropsychiatric measures (AS, r = 0.57; STAI, r = 0.66; MFIS, r = 0.60), while only moderately correlated with convergent measures (MDS-UPDRSd, r = 0.36; HAMDd, r = 0.32; Ps < 0.05). Linear regression analyses revealed standardized measures of anxiety, apathy, and fatigue independently predicted the GDS total score, while depression items (MDS-UPDRSd and HAMDd) failed to reach significance. Three independent factors were identified: Anxiety, Apathy, and Fatigue. These factors were significantly predicted by their respective convergent measures. CONCLUSIONS: Taken together, our findings suggest that the GDS and its subscales appear to primarily measure anxiety, apathy, and fatigue in PD, or alternatively, these symptom dimensions may be predominant in PD-depression. Future research with clinically diagnosed samples is needed to confirm these initial findings.

Spectroscopic Observation of Calcium-Induced Reorientation of Cellobiose Dehydrogenase Immobilized on Electrodes and its Effect on Electrocatalytic Activity.

Cellobiose dehydrogenase catalyzes the oxidation of various carbohydrates and is considered as a possible anode catalyst in biofuel cells. It has been shown that the catalytic performance of this enzyme immobilized on electrodes can be increased by presence of calcium ions. To get insight into the Ca(2+) -induced changes in the immobilized enzyme we employ surface-enhanced vibrational (SERR and SEIRA) spectroscopy together with electrochemistry. Upon addition of Ca(2+) ions electrochemical measurements show a shift of the catalytic turnover signal to more negative potentials while SERR measurements reveal an offset between the potential of heme reduction and catalytic current. Comparing SERR and SEIRA data we propose that binding of Ca(2+) to the heme induces protein reorientation in a way that the electron transfer pathway of the catalytic FAD center to the electrode can bypass the heme cofactor, resulting in catalytic activity at more negative potentials.

The relationship between objective and subjective executive function in Parkinson's disease.

INTRODUCTION: Difficulties in executive functioning (EF) are common in PD; however, the relationship between subjective and objective EF is unclear. Understanding this relationship could help guide clinical EF assessment. This study examined the relationship between subjective self-reported EF (SEF) and objective EF (OEF) and predictors of SEF-OEF discrepancies in PD. METHOD: One-hundred and sixteen non-demented PD participants completed measures of OEF (i.e. problem-solving, cognitive flexibility, inhibition, and working memory) and SEF (Frontal Systems Behavior Scale-Self Executive Dysfunction Subscale). Pearson bivariate correlations and linear regressions were performed to examine the relationship between SEF and OEF and the non-motor symptoms (e.g. mood, fatigue), demographic, and PD characteristic (e.g. MCI status) predictors of discrepancies between OEF and SEF (|OEF minus SEF scores|). Correlates of under-, over-, and accurate-reporting were also explored. RESULTS: Greater SEF complaints and worse OEF were significantly associated (ß =.200, p = .009) and 64% of participants accurately identified their level of OEF abilities. Fewer years of education and greater symptoms of depression, anxiety, and fatigue significantly correlated with greater discrepancies between OEF and SEF. Fatigue was the best predictor of EF discrepancy in the overall sample (ß = .281, p = .022). Exploratory analyses revealed apathy and fatigue associated with greater under-reporting, while anxiety associated with greater over-reporting. CONCLUSIONS: SEF and OEF are significantly related in PD. Approximately 64% of non-demented persons with PD accurately reported their EF skill level, while 28% under-reported and 8% over-reported. SEF-OEF discrepancies were predicted by fatigue in the overall sample. Preliminary evidence suggests reduced apathy and fatigue symptoms relate to more under-reporting, while anxiety relates to greater over-reporting. Given the prevalence of these non-motor symptoms in PD, it is important to carefully consider them when assessing EF in PD.

Frontal-temporal regional differences in brain energy metabolism and mitochondrial function using 31P MRS in older adults.

Aging is a major risk for cognitive decline and transition to dementia. One well-known age-related change involves decreased brain efficiency and energy production, mediated in part by changes in mitochondrial function. Damaged or dysfunctional mitochondria have been implicated in the pathogenesis of age-related neurodegenerative conditions like Alzheimer's disease (AD). The aim of the current study was to investigate mitochondrial function over frontal and temporal regions in a sample of 70 cognitively normal older adults with subjective memory complaints and a first-degree family history of AD. We hypothesized cerebral mitochondrial function and energy metabolism would be greater in temporal as compared to frontal regions based on the high energy consumption in the temporal lobes (i.e., hippocampus). To test this hypothesis, we used phosphorous (31P) magnetic resonance spectroscopy (MRS) which is a non-invasive and powerful method for investigating in vivo mitochondrial function via high energy phosphates and phospholipid metabolism ratios. We used a single voxel method (left temporal and bilateral prefrontal) to achieve optimal sensitivity. Results of separate repeated measures analyses of variance showed 31P MRS ratios of static energy, energy reserve, energy consumption, energy demand, and phospholipid membrane metabolism were greater in the left temporal than bilateral prefrontal voxels. Our findings that all 31P MRS ratios were greater in temporal than bifrontal regions support our hypothesis. Future studies are needed to determine whether findings are related to cognition in older adults.

What does the Dementia Rating Scale-2 measure? The relationship of neuropsychological measures to DRS-2 total and subscale scores in non-demented individuals with Parkinson's disease.

OBJECTIVE: The Dementia Rating Scale-2 (DRS-2) is recommended for assessing global cognition in Parkinson's disease (PD) by the Movement Disorder Society. However, empirical evidence is limited regarding the degree to which the DRS-2 corresponds to traditional neurocognitive domains (i.e., construct validity) in PD. Thus, this study aims to determine the construct validity of the DRS-2 in a non-demented sample of PD patients. METHOD: Patients with PD (n = 359; mean age = 64.50 ± 8.53, education = 14.97 ± 2.73, disease duration = 8.48 ± 4.87, UPDRS Part III motor scale scores = 25.23 ± 10.17) completed the DRS-2 as part of a comprehensive neuropsychological assessment consisting of attention/working memory, executive function, language, delayed recall, and visuoperceptual-spatial skills.Bootstrapped bias-corrected Spearman rho's correlations andhierarchical linear regressions were performed to examine construct validity of DRS-2 total and subscale scores. RESULTS: Speeded measures of set-shifting, rapid word generation to letter and semantic cues, and simple visuoperceptual skills largely accounted for variance in DRS-2 total scores. Most DRS-2 subscale scores showed weak relationships with theoretically related neuropsychological measures. CONCLUSIONS: DRS-2 total scores reflect impairment across a range of cognitive domains (i.e., executive, language, and visuoperception), while DRS-2 subscale scores have limited construct validity. Together, the DRS-2 does not appear to have utility beyond screening for global cognition in PD.

Early rapid eye movement sleep behavior disorder predicts incident cognitive impairment in Parkinson's disease across ages.

This study demonstrated possible rapid eye movement sleep behavior disorder (RBD)'s relationship to longitudinal, incident cognitive impairment in the Parkinson's Progression Markers Initiative (PPMI) database. Age did not moderate this relationship, suggesting that RBD serves as a cognitive risk factor across individuals of all ages with recently diagnosed Parkinson's disease.

Frontal adenosine triphosphate markers from 31P MRS are associated with cognitive performance in healthy older adults: preliminary findings.

Aging is associated with declines in mitochondrial efficiency and energy production which directly impacts the availability of adenosine triphosphate (ATP), which contains high energy phosphates critical for a variety of cellular functions. Previous phosphorous magnetic resonance spectroscopy (31P MRS) studies demonstrate cerebral ATP declines with age. The purpose of this study was to explore the functional relationships of frontal and posterior ATP levels with cognition in healthy aging. Here, we measured frontal and posterior ATP levels using 31P MRS at 3 Tesla (3 T) and assessed cognition using the Montreal Cognitive Assessment (MoCA) in 30 healthy older adults. We found that greater frontal, but not posterior, ATP levels were significantly associated with better MoCA performance. This relationship remained significant after controlling for age, sex, years of education, and brain atrophy. In conclusion, our findings indicate that cognition is related to ATP in the frontal cortex. These preliminary findings may have important implications in the search for non-invasive markers of in vivo mitochondrial function and the impact of ATP availability on cognition. Future studies are needed to confirm the functional significance of regional ATP and cognition across the lifespan.

Unpacking the NIH Toolbox Emotion Battery in Persons With Parkinson's disease.

OBJECTIVE: Examine the relationship between the National Institutes of Health Toolbox Emotion Battery (Emotion Toolbox) and traditional measures in Parkinson's disease (PD). METHOD: Persons with PD (n = 30) and cognitively healthy older adults (OA; n = 40) completed the Emotion Toolbox consisting of Well-Being, Negative Affect, and Social Satisfaction scores along with traditional measures of depression (Beck Depression Inventory-II [BDI-II]), anxiety (State-Trait Anxiety Inventory [STAI]), and apathy (Apathy Scale [AS]); total raw scores). RESULTS: Separate bootstrapped analyses of covariance indicated that the PD group scored higher on BDI-II and STAI-State compared to OA (ps < .01); groups did not differ on Emotion Toolbox. In the PD group, bootstrapped partial correlations indicated that Negative Affect was positively related to BDI-II and STAI (ps ≤ .001). Social Satisfaction was negatively related to BDI-II and STAI-Trait (.05 < ps < .004). Psychological Well-Being was negatively related to BDI-II, AS, and STAI (p < .004). No relationships emerged in OA. In the PD group, separate binary logistic regressions showed that traditional measures (BDI-II, AS, and STAI-Trait) correctly classified 79.6% those with formal psychiatric diagnoses (presence vs. absence; p < .011), whereas Emotion Toolbox measures correctly classified 73.3% (p < .019). CONCLUSIONS: The Emotion Toolbox showed moderate-strong correlations with traditional measures in persons with PD. Even so, it did not capture the group differences between PD and OA and had a somewhat lower classification accuracy rate for persons with PD who had a formal psychiatric diagnosis than traditional measures. Together, findings question the utility of the Emotion Toolbox as a stand-alone emotion screener in PD.

Age-related differences in memory for "who," "when," and "where" are detectable in middle-aged adults.

Our study examined age-related differences across the adult lifespan using a recently developed test assessing memory for "who, when, and where" in addition to associations among these elements. Young (ages 18-25), middle-aged (ages 40-55), and older adults (ages 60+) were asked to remember a sequence of pictures of different faces paired with different places and place the pairs in the correct sequence. Young adults remembered significantly mores face-place pairs in the correct sequence than middle-aged (p < .05) and older adults (p < .05), but there were no significant differences between middle-aged and older adults. Furthermore, young adults remembered significantly more face-place pairs irrespective of sequence than older adults (p < .05). However, there were no other significant differences among the groups.Using a rapidly administered test that integrates aspects of everyday episodic memory, we found evidence for age-related differences in test performance beginning in middle age.

Differential contributions of depression, apathy, and anxiety to neuropsychological performance in Parkinson's disease versus essential tremor.

INTRODUCTION: Mood symptoms are common features of Parkinson's disease (PD) and essential tremor (ET) and have been linked to worse cognition. The goals of the present study were to compare the severity of anxiety, apathy, and depressive symptoms in PD, ET, and healthy controls (HC) and to examine differential relationships between mood and cognition. METHOD: Older adults with idiopathic PD (N = 448), ET (N = 128), or HC (N = 136) completed a multi-domain neuropsychological assessment consisting of memory, executive function, and attention/working memory domains. Participants also completed self-reported mood measures. Between-group differences in mood and cognition were assessed, and hierarchical regression models were conducted to examine relationships between mood and cognition in each group. RESULTS: Relative to the HC group, the PD and ET groups reported more mood symptoms and scored lower across all cognitive measures. There were no differences between the two movement disorder groups. Mood variables explained 3.9-13.7% of the total variance in cognitive domains, varying by disease group. For PD, apathy was the only unique predictor of executive function (ß = -.114, p = .05), and trait anxiety was the only unique predictor of attention/working memory (ß = -.188, p < .05). For ET, there were no unique predictors, though the overall models significantly predicted performance in the executive function and attention/working memory domains. CONCLUSIONS: In a large cohort of ET and PD, we observed that the two groups had similar self-reported mood symptoms. Mood symptoms were differentially associated with cognition in PD versus ET. In PD, increased apathy was associated with worse executive function and higher trait anxiety predicted worse attention/working memory. For ET, there were no unique predictors, though the overall mood symptom severity was related to cognition. Our study highlights the importance of considering the relationship between mood and neuropsychological performance in individuals with movement disorders.

Cognitive subtypes in individuals with essential tremor seeking deep brain stimulation.

Objective: Essential tremor (ET) is a common neurological disorder that has been associated with 60% increased risk of developing dementia. The goals of the present study were to: (a) learn whether individuals with advanced ET symptoms seeking deep brain stimulation (DBS) surgery would fall into distinct cognitive subgroups, and (b) learn how empirically derived subgroups map onto criteria for mild cognitive impairment (MCI). Method: Patients with ET (N = 201; mean age = 68.9 ± 8.9 years) undergoing pre-surgical evaluation for DBS completed a multi-domain neurocognitive assessment consisting of memory, executive function, visuospatial skill, language, and processing speed. Two cluster analytic approaches (K-means, hierarchical) were independently conducted to classify cognitive patterns using domain composites. Demographics, clinical characteristics, and proportion of cases meeting neuropsychologically defined criteria for MCI were examined among clusters. Results: A three-cluster solution reflected a Low Executive group (N = 64), Low Memory Multi-Domain group (N = 41), and Cognitively Normal group (N = 96). The Cognitively Normal group was older and more educated, with a higher Dementia Rating Scale-2 score. In total, 27.4% of participants met criteria for MCI. Of the MCI cases, most were in the Low Executive (41.8%) or Low Memory Multi-Domain groups (49.1%). In the latter, 65.9% of its members were classified as MCI versus 35.9% in the Low Executive group. Conclusions: Our study identified three cognitive subtypes of ET patients presenting for DBS. Future work should examine the subgroups for progression to dementia, particularly the Low Memory Multi-Domain subgroup which may be at highest risk.

Circulating carotenoids are associated with favorable lipid and fatty acid profiles in an older population at high cardiovascular risk.

Carotenoid intake has been reported to be associated with improved cardiovascular health, but there is little information on actual plasma concentrations of these compounds as biomarkers of cardiometabolic risk. The objective was to investigate the association between circulating plasma carotenoids and different cardiometabolic risk factors and the plasma fatty acid profile. This is a cross-sectional evaluation of baseline data conducted in a subcohort (106 women and 124 men) of an ongoing multi-factorial lifestyle trial for primary cardiovascular prevention. Plasma concentrations of carotenoids were quantified by liquid chromatography coupled to mass spectrometry. The associations between carotenoid concentrations and cardiometabolic risk factors were assessed using regression models adapted for interval-censored variables. Carotenoid concentrations were cross-sectionally inversely associated with serum triglyceride concentrations [-2.79 mg/dl (95% CI: -4.25, -1.34) and -5.15 mg/dl (95% CI: -7.38, -2.93), p-values = 0.0002 and <0.00001 in women and men, respectively], lower levels of plasma saturated fatty acids [-0.09% (95% CI: -0.14, -0.03) and -0.15 % (95% CI: -0.23, -0.08), p-values = 0.001 and 0.0001 in women and men, respectively], and higher levels of plasma polyunsaturated fatty acids [(0.12 % (95% CI: -0.01, 0.25) and 0.39 % (95% CI: 0.19, 0.59), p-values = 0.065 and 0.0001 in women and men, respectively] in the whole population. Plasma carotenoid concentrations were also associated with higher plasma HDL-cholesterol in women [0.47 mg/dl (95% CI: 0.23, 0.72), p-value: 0.0002], and lower fasting plasma glucose in men [-1.35 mg/dl (95% CI: -2.12, -0.59), p-value: 0.001].

Delineation of Apathy Subgroups in Parkinson's Disease: Differences in Clinical Presentation, Functional Ability, Health-related Quality of Life, and Caregiver Burden.

BACKGROUND: Apathy is a prevalent, multidimensional neuropsychiatric condition in Parkinson's disease (PD). Several authors have proposed apathy subtypes in PD, but no study has examined the classification of PD patients into distinct apathy subtypes, nor has any study examined the clinical utility of doing so. OBJECTIVES: The current study used a data-driven approach to explore the existence and associated clinical characteristics of apathy subtypes in PD. METHOD: The Apathy Scale (AS) was administered to 157 non-demented individuals with PD. Participants were classified into apathy subgroups through cluster analysis. Differences among apathy subtypes on external clinical indicators were explored across apathy subgroups. RESULTS: Individuals with PD were classified into three subgroups: a Non-Apathetic group with low levels of apathy symptoms, a Low Interest/Energy group, characterized by elevated symptoms of low interest/energy and minimal low initiation/emotional indifference symptoms, and a Low Initiation group, characterized by an absence of low interest/energy symptoms and elevated levels of low initiation/emotional indifference symptoms. Both Low Interest/Energy and Low Initiation groups exhibited worse depression, fatigue, anxiety, health-related quality of life, and caregiver burden than the Non-Apathetic subgroup. The Low Initiation group exhibited worse overall cognition, emotional well-being, state anxiety, communicative ability, and functional ability than the Low Interest/Energy group. Importantly, disease-related characteristics did not differ across apathy symptom subgroups. CONCLUSIONS: Non-demented PD patients can be separated into distinct apathy symptom subgroups, which are differentially associated with important clinical variables. Apathy subgroup membership may reflect disruption to different neural systems independent of disease progression.