Olfactory Deficits in Neurologic Disease

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).

Study Overview

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

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 Type: Observational
• Enrollment (Actual): 201

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02129
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

1. 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.
2. Diagnosis of familial or sporadic ALS per El Escorial Criteria or individuals with known gene mutations associated with ALS (regardless of clinical phenotype).
3. Age-matched controls
4. Males and females with a minimum age of enrollment of 18 years. There is no maximum age of enrollment.

Description

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 Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Neurodegenerative disease; Participants with a diagnosis of Probable Alzheimer's Disease, prodromal Alzheimer's Disease, Frontotemporal Dementia, Mild Cognitive Impairment, Dementia with Lewy Bodies, mild and moderate/severe TBI, and familial or sporadic ALS per El Escorial Criteria or individuals with known gene mutations associated with ALS.
Age-matched controls; Healthy participants with no diagnosis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Selective loss of episodic odor memory (Poor POEM status) will correlate with imaging and neuropsychological signs of neurodegenerative disease.	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.	9 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correct responses on the episodic memory of odor percepts measure will correlate with entorhinal cortical thickness, and neuropsychological test results.	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.	9 years
Correct responses on the odor percept identification task will correlate with imaging and neuropsychological signs of neurodegenerative disease.	Compare number of trials of odors correctly identified will correlate with entorhinal cortical thickness, and neuropsychological test results.	9 years
Correct responses on the odor discrimination task will correlate with imaging and neuropsychological signs of neurodegenerative disease.	Compare number of trials correctly discriminated will correlate with entorhinal cortical thickness, and neuropsychological test results.	9 years

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital

Publications and helpful links

General Publications

• Dhilla Albers A, Asafu-Adjei J, Delaney MK, Kelly KE, Gomez-Isla T, Blacker D, Johnson KA, Sperling RA, Hyman BT, Betensky RA, Hastings L, Albers MW. Episodic memory of odors stratifies Alzheimer biomarkers in normal elderly. Ann Neurol. 2016 Dec;80(6):846-857. doi: 10.1002/ana.24792. Epub 2016 Nov 23.

Study record dates

Study Major Dates

• Study Start (Actual): August 10, 2011
• Primary Completion (Actual): January 3, 2017
• Study Completion (Actual): July 3, 2020

Study Registration Dates

• First Submitted: April 7, 2017
• First Submitted That Met QC Criteria: August 18, 2021
• First Posted (Actual): August 24, 2021

Study Record Updates

• Last Update Posted (Actual): August 24, 2021
• Last Update Submitted That Met QC Criteria: August 18, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Neurologic Manifestations; Wounds and Injuries; Neurobehavioral Manifestations; Neurocognitive Disorders; Neuromuscular Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Craniocerebral Trauma; Trauma, Nervous System; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Dementia; Tauopathies; Cognition Disorders; Language Disorders; Communication Disorders; Speech Disorders; Frontotemporal Lobar Degeneration; Aphasia; Brain Injuries; Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Brain Injuries, Traumatic; Nervous System Diseases; Alzheimer Disease; Cognitive Dysfunction; Lewy Body Disease; Frontotemporal Dementia; Aphasia, Primary Progressive; Pick Disease of the Brain
• Other Study ID Numbers: 2011P001296

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No