Olfactory Deficits in Neurologic Disease

Completed

• Conditions: Traumatic Brain Injury; Mild Cognitive Impairment; Alzheimer Disease; Lewy Body Disease; Amyotrophic Lateral Sclerosis; Frontotemporal Dementia

• Registration Number: NCT05019014
• Lead Sponsor: Massachusetts General Hospital

Brief Summary

The goal of this study is to examine olfactory function in preclinical subjects or individuals with neurological diseases such as Probable Alzheimer's Disease (PRAD), Frontotemporal Dementias (FTD), Dementia with Lewy Bodies (DLB), Traumatic Brain Injury (TBI), and Amyotrophic Lateral Sclerosis (ALS).

Detailed Description

The goal of this study is to examine olfactory function in preclinical subjects \[n = 150\] or individuals with neurological diseases such as Probable Alzheimer's Disease (PRAD) \[n = 50\], Mild Cognitive Impairment \[n = 50\], Frontotemporal Dementias (FTD) \[n = 50\], and Dementia with Lewy Bodies (DLB) \[n = 50\] that are part of the Longitudinal Research Cohort of the Massachusetts Alzheimer's Disease Research Center (IRB Protocol #: 1999P003693), are being treated by neurologists in the Memory Disorders or Movements Disorders Clinics at MGH, or are part of the community. The investigators will also examine individuals with Amyotrophic Lateral Sclerosis (ALS) \[n = 50\], ALS probands \[n = 50\], and ALS family controls \[n = 50\] that are part of the Neurological Clinical Research Institute (NCRI) protocols "NeuroBANK" (2013P001670), "Repository" (2006P000982), and "Longitudinal CSF" (2011P000785). Olfactory data will be correlated with existing data collected under the above-mentioned IRB protocols. The investigators will also be studying olfactory function in patients with mild TBI \[n=50\], and moderate and severe TBI \[n=50\], that are patients of Spaulding Rehabilitation Network. Specifically, the investigators will assess odor discrimination, odor identification, and episodic olfactory memory, using the OLFACT olfactometer run by a laptop or through a wireless iPad interface (Osmic Enterprises). Olfactory data collected from patients and age-matched control subjects \[n = 100\] will be correlated with existing structural MRI, functional MRI, and PET imaging data and with existing neuropsychological data collected under IRB protocols 1999P003693 and 2007P002107 ("Neurological Disease Registry"), NeuroBANK™ IRB protocol 2013P001670, Repository IRB protocol 2006P000982, and Longitudinal CSF IRB protocol 2011P000785.

Study Timeline

• Study Start: 2011-08-10
• Primary Completion: 2017-01-03
• Study First Submitted: 2017-04-07
• Study Completion: 2020-07-03
• Status Verified: 2021-08
• Study First Submitted QC: 2021-08-18
• Last Update Submitted: 2021-08-18
• Study First Posted: 2021-08-24
• Last Update Posted: 2021-08-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 201

Inclusion Criteria

• Diagnosis of Probable Alzheimer's Disease, prodromal Alzheimer's Disease, Frontotemporal Dementia, Mild Cognitive Impairment, or Dementia with Lewy Bodies or mild and moderate/severe TBI.
• Diagnosis of familial or sporadic ALS per El Escorial Criteria or individuals with known gene mutations associated with ALS (regardless of clinical phenotype).
• Age-matched controls
• Males and females with a minimum age of enrollment of 18 years. There is no maximum age of enrollment.

Exclusion Criteria

• Primary pulmonary disease such as severe emphysema or asthma not under good medical control.
• Current sinusitis or common cold or upper respiratory infection, nasal polyps, or sinusitis.
• Traumatic or congenital anosmia
• Current or recent (past 6 months) alcohol or substance dependence. A prior history of alcohol or substance abuse will not be grounds for exclusion.
• Pregnancy
• Severe cognitive dysfunction
• Pneumocephalus
• Basilar skull fracture
• Known CSF leak
• Facial fractures to include Lefort I, II or III

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Selective loss of episodic odor memory (Poor POEM status) will correlate with imaging and neuropsychological signs of neurodegenerative disease.	9 years	Poor POEM status determined by comparing the predicted POEM score with the actual POEM score will correlate with entorhinal cortical thickness, and neuropsychological test results.

Secondary Outcome Measures

Name	Time	Method
Correct responses on the odor discrimination task will correlate with imaging and neuropsychological signs of neurodegenerative disease.	9 years	Compare number of trials correctly discriminated will correlate with entorhinal cortical thickness, and neuropsychological test results.
Correct responses on the episodic memory of odor percepts measure will correlate with entorhinal cortical thickness, and neuropsychological test results.	9 years	Compare number of trials correctly discriminated; compare number of odors correctly identified; and compare number of hits (accurate episodic memory of exposure to odor), and number of correct rejections (accurate episodic memory of non-exposure to odor). Correlate familiarity with number of hits and correct rejections.
Correct responses on the odor percept identification task will correlate with imaging and neuropsychological signs of neurodegenerative disease.	9 years	Compare number of trials of odors correctly identified will correlate with entorhinal cortical thickness, and neuropsychological test results.

Trial Locations

Locations (1)

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States