Publications by authors named "Klinger H"

Elucidating the downstream impact of exogenous hormones on the aging brain will have far-reaching consequences for understanding why Alzheimer's disease (AD) predominates in women almost twofold over men. We tested the extent to which menopausal hormone therapy (HT) use is associated with later-life amyloid-β (Aβ) and tau accumulation using PET on  = 146 baseline clinically normal women, aged 51 to 89 years. Women were scanned over a 4.

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Impulse control disorders (ICDs) are frequent and particularly distressing neuropsychiatric symptoms in patients with Parkinson's disease (PD) which are related to impaired behavioural inhibition. Multiple PET imaging studies indicate that striatal dopaminergic abnormalities contribute to hyperdopaminergic functioning in PD patients with ICD (PDICD+) and to the dysregulation of the limbic fronto-striatal networks which are critical for reward-related decision impulsivity. However, the serotonergic system is central to response inhibition and plays a critical role in neuropsychiatric symptoms in PD, but its role remains undetermined in PDICD.

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Importance: Alzheimer disease (AD) predominates in females at almost twice the rate relative to males. Mounting evidence in adults without AD indicates that females exhibit higher tau deposition than age-matched males, particularly in the setting of elevated β-amyloid (Aβ), but the evidence for sex differences in tau accumulation rates is inconclusive.

Objective: To examine whether female sex is associated with faster tau accumulation in the setting of high Aβ (as measured with positron emission tomography [PET]) and the moderating influence of sex on the association between APOEε4 carrier status and tau accumulation.

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Introduction: Specific features of subjective cognitive decline (SCD-plus) have been proposed to indicate an increased risk of preclinical Alzheimer's disease (AD). However, few studies have examined how these features relate to AD biomarkers in cognitively unimpaired (CU) older adults.

Methods: Meta-analyses were performed using cross-sectional data from nine cohorts (n = 7219, mean age (SD): 71.

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Cognitive resilience (CR) describes the phenomenon of individuals evading cognitive decline despite prominent Alzheimer's disease neuropathology. Operationalization and measurement of this latent construct is non-trivial as it cannot be directly observed. The residual approach has been widely applied to estimate CR, where the degree of resilience is estimated through a linear model's residuals.

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Article Synopsis
  • The study investigates the relationship between changes in β-amyloid (Aβ) levels and cognitive decline over time, highlighting that Aβ accumulation is linked to subsequent cognitive deterioration in older adults.
  • Researchers utilized sophisticated statistical models on data from a long-term study of 352 cognitively normal older participants, revealing that short-term changes in Aβ are more impactful on cognition than traditional measurements of Aβ burden and tau levels.
  • Contrary to previous findings, the study found no significant link between tau levels in the medial temporal lobe and cognitive performance, suggesting that understanding cognitive decline requires looking at dynamic changes rather than static measures.
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Background And Purpose: Disabling dystonia despite optimal medical treatment is common in Wilson disease (WD). No controlled study has evaluated the effect of deep brain stimulation (DBS) on dystonia related to WD. This study was undertaken to evaluate the efficacy of DBS on dystonia related to WD.

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Article Synopsis
  • Cognitive resilience is when people don't show mental decline even if they have signs of Alzheimer's in their brains.
  • Measuring cognitive resilience is tricky because it can't be seen directly, and one common method used might give wrong results.
  • The new method we suggest uses machine learning to improve how we measure cognitive resilience, making it more accurate and relying less on guesses about the data.
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Background: Stronger resting-state functional connectivity of the default mode and frontoparietal control networks has been associated with cognitive resilience to Alzheimer's disease related pathology and neurodegeneration in smaller cohort studies.

Objectives: We investigated whether these networks are associated with longitudinal CR to AD biomarkers of beta-amyloid (Aβ).

Design: Longitudinal mixed.

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Article Synopsis
  • This study investigates cognitive resilience (CR) to Alzheimer's disease (AD) in cognitively healthy older adults by analyzing imaging biomarkers and cognitive data over time using latent class mixture modeling.
  • The research involved 200 participants from the Harvard Aging Brain Study, who were categorized into three subgroups based on their cognitive trajectories: Normal, Resilient, and Declining, with the Resilient group showing higher cognitive performance and stability.
  • The findings suggest that leveraging imaging and cognitive assessments can effectively identify different levels of CR in preclinical AD stages, which could have implications for future research and interventions.
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  • This study investigates the relationship between self-reported cognitive decline and tau deposition in individuals with preclinical Alzheimer disease (AD), building on prior findings about β-amyloid (Aβ) status.
  • The research involved 675 cognitively unimpaired participants who completed assessments to examine the connections between tau levels and cognitive function, while accounting for factors like age and education.
  • Results indicated that higher tau levels in both the medial temporal lobe and neocortex were linked to increased cognitive function scores reported by both participants and their study partners, particularly in those with elevated Aβ levels.
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Few studies have considered the influence of motor sign asymmetry on motivated behaviors in de novo drug-naïve Parkinson's disease (PD). We tested whether motor sign asymmetry could be associated with different motivated behavior patterns in de novo drug-naïve PD. We performed a cross-sectional study in 128 de novo drug-naïve PD patients and used the Ardouin Scale of Behavior in Parkinson's disease (ASBPD) to assess a set of motivated behaviors.

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The Face Name Associative Memory Exam (FNAME) was introduced into the NIH Toolbox as part of the ARMADA study and establishes normative data for diverse participants, ages 64 to 85+, and proposes cutoff scores between biomarker positive versus negative (+/-) groups. The FNAME was administered to 257 participants across the clinical spectrum with 122 having amyloid biomarkers. Linear regression explored the association between demographics and FNAME and between amyloid (+/-) groups.

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Background: Impulse control disorders (ICDs) are frequently encountered in Parkinson's disease (PD).

Objectives: We aimed to assess whether clonidine, an α2-adrenergic receptor agonist, would improve ICDs.

Methods: We conducted a multicentre trial in five movement disorder departments.

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Introduction: The associations between subjective cognitive decline (SCD), cognition, and amyloid were explored across diverse participants in the A4 study.

Methods: Five thousand one hundred and fifty-one non-Hispanic White, 262 non-Hispanic Black, 179 Hispanic-White, and 225 Asian participants completed the Preclinical Alzheimer Cognitive Composite (PACC), self- and study partner-reported Cognitive Function Index (CFI). A subsample underwent amyloid positron emission tomography ( F-florbetapir) (N = 4384).

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Importance: Postmenopausal females represent around 70% of all individuals with Alzheimer disease. Previous literature shows elevated levels of tau in cognitively unimpaired postmenopausal females compared with age-matched males, particularly in the setting of high β-amyloid (Aβ). The biological mechanisms associated with higher tau deposition in female individuals remain elusive.

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Depression is one of the most frequent and burdensome non-motor symptoms in Parkinson's disease (PD), across all stages. Even when its severity is mild, PD depression has a great impact on quality of life for these patients and their caregivers. Accordingly, accurate diagnosis, supported by validated scales, identification of risk factors, and recognition of motor and non-motor symptoms comorbid to depression are critical to understanding the neurobiology of depression, which in turn determines the effectiveness of dopaminergic drugs, antidepressants and non-pharmacological interventions.

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In this one-year prospective study, Parkinson's disease (PD) patients with or without mania following STN-DBS were compared to investigate risk and etiological factors, clinical management and consequences. Eighteen (16.2%) out of 111 consecutive PD patients developed mania, of whom 17 were males.

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Background: Parkinson's disease mild cognitive impairment (PD-MCI) is frequent and heterogenous. There is no consensus about its influence on subthalamic deep brain stimulation (STN-DBS) outcomes.

Objective: To determine the prevalence of PD-MCI and its subtypes in candidates to STN-DBS.

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Background: Previous studies described a parkinsonian personality characterized as rigid, introverted, and cautious; however, little is known about personality traits in de novo Parkinson's disease (PD) patients and their relationships with motor and neuropsychiatric symptoms.

Objective: To investigate personality in de novo PD and explore its relationship with PD symptoms.

Methods: Using Cloninger's biosocial model, we assessed personality in 193 de novo PD patients.

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Article Synopsis
  • Fatigue is a common and significant issue experienced by patients in the early stages of Parkinson's disease (PD), impacting their quality of life significantly.
  • A study involving 197 new PD patients showed that fatigue correlates strongly with higher levels of apathy and depression, as well as anxiety, with nearly 29% of patients reporting fatigue.
  • The findings suggest that fatigue should be considered as a key component of the neuropsychiatric triad (apathy, depression, anxiety) in PD, indicating a need for better management strategies.
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  • This study investigates the progression of dopaminergic and serotonergic dysfunction in newly diagnosed Parkinson's disease (PD) patients with or without apathy and its impact on their motor and nonmotor symptoms.
  • Using a longitudinal study with PET scans, researchers found that while both patient groups experienced similar progression in motor issues, apathetic patients showed compensatory changes in serotonergic function that helped reduce their apathy over time.
  • Overall, results suggest that serotonergic plasticity may play a role in reversing apathy in PD patients, highlighting the need for further exploration of these compensatory mechanisms after starting dopamine replacement therapy.
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Background: Deep brain stimulation of the sub-thalamic nucleus (DBS-STN) reduces symptoms in Parkinson's disease (PD) patients with motor fluctuations. However, some patients may not feel ameliorated afterwards, despite an objective motor improvement. It is thus important to find new predictors of patients' quality of life (QoL) amelioration after DBS-STN.

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Background: Parkinson's disease (PD) is characterized by heterogeneous motor and nonmotor manifestations related to alterations in monoaminergic neurotransmission systems. Nevertheless, the characterization of concomitant dopaminergic and serotonergic dysfunction after different durations of Parkinson's disease, as well as their respective involvement in the expression and severity of neuropsychiatric signs, has gained little attention so far.

Methods: To fill this gap, we conducted a cross-sectional study combining clinical and dual-tracer positron emission tomography (PET) neuroimaging approaches, using radioligands of dopamine ([ C]-N-(3-iodoprop-2E-enyl)-2-beta-carbomethoxy-3-beta-(4-methylphenyl)-nortropane) ([ C]PE2I) and serotonin ([ C]-N,N-dimethyl-2-(-2-amino-4-cyanophenylthio)-benzylamine) ([ C]DASB) reuptake, after different durations of Parkinson's disease (ie, in short-disease duration drug-naive de novo (n = 27, 0-2 years-duration), suffering from apathy (n = 14) or not (n = 13); intermediate-disease duration (n = 15, 4-7 years-duration) and long-disease duration, non-demented (n = 15, 8-10 years-duration) patients).

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