# Clinical Pathological Study of Cognitive Impairment in Essential Tremor

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2021 · $1,026,260

## Abstract

Essential tremor (ET) is among the most prevalent neurological diseases. Although it was long considered a
purely motor disorder, ET is increasingly being regarded as more complex, with an emerging recognition of
cognitive dysfunction. While cognitive deficits can be mild, other patients dement. Several epidemiological
studies reveal a higher prevalence of mild cognitive impairment (MCI) and 1.5 to 2-fold increased risk of
Alzheimer's disease (AD) in ET. Yet the study of cognition/dementia in ET is nascent. Our data are limited and
patchy - the most basic “whats” (i.e., clinical features, clinical course) and “whys” (i.e., postmortem basis) are
uncharted. In sum, there is a cognitive side to ET, and we know little about it. For the past 4 years, we have
established and begun to follow an ET cohort to address several of these unknowns (Clinical-Pathological
Study of Cognitive Impairment in ET, COGNET). COGNET is the largest (230 enrolled; 195 living), most
comprehensive, and only active prospective cohort of ET patients. Key elements are detailed, motor-free,
longitudinal cognitive testing, consensus cognitive diagnoses (normal cognition [NC], MCI, dementia), and
autopsy data. The study called for a baseline and two follow-up assessments. Currently, mean follow-up from
baseline is only 1.50 ± 0.21 years (range = 0.31 - 2.29). Thirty-five died. The data have allowed us to begin to
characterize the cognitive deficits in ET and study their pathological bases. Yet, there remain large, obvious
gaps in knowledge. First, clinically, are the cognitive impairments in ET progressive? Do they progress at a
faster rate than in the general population? What are the conversion rates to MCI and dementia? What are the
clinical predictors of cognitive decline? Are cognitive deficits characteristic of AD predictive of worse clinical
outcomes? It turns out that we know virtually nothing about the predictors, course and outcomes of cognitive
impairments in ET, and such information cannot simply be taken from the general population. With a cohort
now successfully assembled and longitudinal cognitive phenotyping ongoing, COGNET is poised to tackle
important prognostic issues regarding the predictors and dynamics of cognitive deficits in ET (Aim 1). Second,
pathologically, what is the basis for cognitive deficits in ET? Our studies point to heterogeneous deficits with
heterogeneous bases, including AD pathologies. We only have 35 postmortems, and our nascent study of the
pathological basis for cognitive deficits must grow and come to maturity (Aim 2). We now propose to continue
this cohort, adding new measures to characterize the predictors and outcomes of cognitive impairments in ET.
We propose enrolling 100 additional ET cases (proposed total n = 295). AIM 1. To provide the first long-term
prospective, longitudinal characterization of cognition in ET to address unanswered prognostic questions about
cognitive impairment in ET (e.g., conversion rates to MCI and dementia)...

## Key facts

- **NIH application ID:** 10248571
- **Project number:** 5R01NS086736-09
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** STEPHANIE Ann COSENTINO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,026,260
- **Award type:** 5
- **Project period:** 2014-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10248571

## Citation

> US National Institutes of Health, RePORTER application 10248571, Clinical Pathological Study of Cognitive Impairment in Essential Tremor (5R01NS086736-09). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10248571. Licensed CC0.

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