Alzheimer’s-related Changes in non-Demented Essential Tremor Patients vs. Controls: Links Between Tau and Tremor?

Parkinsonism & Related Disorders (Impact Factor: 3.97). 06/2014; 20(6). DOI: 10.1016/j.parkreldis.2014.03.003


In addition to tremor, patients with essential tremor (ET) may exhibit non-motor features, including a range of cognitive deficits. Several prospective, population-based epidemiological studies have reported an association between ET and incident dementia, especially Alzheimer’s disease (AD). Moreover, in a brain repository-based study, a larger than expected proportion of ET patients also developed pathological changes characteristic of progressive supranuclear palsy, further suggesting a link between ET and tau pathology.

We selected a group of ET patients that were free of dementia clinically and without AD on postmortem examination. Our hypothesis was that neuronal tauopathic burden would be higher in the brains of these ET patients compared to controls. We compared Braak stage for neuronal tangles and Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) scores for neuritic plaques in the two groups.

The two groups were similar in age (82.6±6.0 vs. 80.4±8.1, p=0.22). The 40 ET patients had a higher Braak neurofibrillary stage than 32 controls (means: 2.2 ± 1.2 vs. 1.2 ± 1.1; medians: 2.0 vs. 1.0, p <0.001). Meanwhile, CERAD scores for neuritic plaques were similar in patients and controls (means: 0.6 ± 0.9 vs. 0.5 ± 0.6; medians: 0.0 vs. 0.0, p = 0.83).

While ET itself is not a tauopathy (i.e., a neurodegenerative disorder among whose main features are accumulation of hyperphosphorylated tau protein), ET may predispose individuals to accumulate more widespread cellular tau aggregates, and thus tau could play a central role in the cognitive impairment that can accompany ET.

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    ABSTRACT: Background: Non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to be inversely related to Parkinson's disease and Alzheimer's disease, both of which may share common mechanisms with essential tremor (ET). Use of these medications has not been studied in ET cases vs. controls. Objective: To investigate the relationships between NSAID (esp. ibuprofen) and aspirin use and ET. Methods: Subjects were enrolled in a case-control study of the environmental epidemiology of ET at the Columbia University Medical Center (CUMC; 2009-2014). We compared 92 ET cases to 107 controls (∼1:1 matching) in terms of self-reported NSAID (esp. ibuprofen) and aspirin use. Results: The proportion of NSAID or aspirin users (current or past) was similar in ET cases and controls (for current user, p = 0.66; for past user, p = 0.90). Among users, however, the total dosage of ibuprofen (frequency in past year × number of tablets taken at a time × typical average strength of tablets) was higher in controls than ET cases (p = 0.04). ET cases and controls did not differ with respect to aspirin use in the past year. Conclusion: The proportion of NSAID or aspirin users did not differ in ET cases or controls; yet interestingly, ibuprofen use was less in ET cases than in controls. The latter raises the possibility that ibuprofen use could have a potential protective role in ET. © 2014 S. Karger AG, Basel.
    No preview · Article · Nov 2014 · Neuroepidemiology
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    ABSTRACT: The aim of this study was to test plasma insulin-like growth factor 1 (IGF-1) change in Parkinson's disease (PD) and essential tremor (ET), and assess the association of plasma IGF-1 level with motor and nonmotor symptoms in PD and ET. Plasma IGF-1 was measured in 100 PD patients, 40 ET patients, and 76 healthy controls. Motor and nonmotor symptoms were assessed by different scales. Spearman correlation test and linear logistic model were used to analyze the correlation of plasma IGF-1 with motor and nonmotor symptoms of PD and ET. The plasma IGF-1 level was significantly increased in PD compared to healthy controls and ET patients. In addition, low plasma IGF-1 was correlated with low Mini-Mental State Examination (MMSE) scores in PD patients. However, no correlation was found between plasma IGF-1 and MMSE scores in ET patients. Plasma IGF-1 increased significantly in PD but remained unchanged in ET. A low plasma IGF-1 level was associated with poor cognitive performance in PD but not in ET patients. © 2015 S. Karger AG, Basel.
    No preview · Article · Apr 2015 · Dementia and Geriatric Cognitive Disorders