Olfactory Deficits and Donepezil Treatment in Cognitively Impaired Elderly

Completed · Phase 4

Conditions studied: Alzheimer Disease, Mild Cognitive Impairment, Delirium, Dementia, Amnestic, Cognitive Disorders

In brief

Olfactory identification deficits occur in patients with Alzheimer's disease (AD), are associated with disease severity, predict conversion from mild cognitive impairment (MCI) to AD and are associated with healthy elderly subjects developing MCI. Odor (olfactory) identification deficits may reflect degeneration of cholinergic inputs to the olfactory bulb and other olfactory brain regions. Acetylcholinesterase inhibitors (ACheI) like donepezil show modest effects in improving cognition but can be associated with adverse effects and increased burden and costs because of the need for prolonged, often lifelong, treatment. Converging findings on odor identification test performance (UPSIT, scratch and sniff 40-item test) from four pilot studies, including two of our own, suggest that acute change in the UPSIT in response to an anticholinergic challenge (atropine nasal spray), incremental change over 8 weeks, and even the baseline UPSIT score by itself, may predict cognitive improvement with ACheI treatment in MCI and AD. If change in odor identification deficits can help to identify which patients should receive ACheI treatment, this simple inexpensive approach will advance the goal of improving personalized treatment, improve selection and monitoring of patients for ACheI treatment, reduce needless ACheI exposure with risk of side effects, and decrease health care costs.

Key facts

Study ID: NCT01951118
Run by: New York State Psychiatric Institute
People needed: 121
Starts: 2013-10-01
Expected to finish: 2019-05-01
Last updated by the study team: 2020-07-13

Who can join

Age: 55 and older, up to 95. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Of either sex, age 55-95 years old
Patients who meet criteria for amnestic mild cognitive impairment by meeting all of the following:
(i) subjective memory complaints (ii) Wechsler Memory Scale-III Logical Memory combined Story A + B immediate recall score or combined Story A + B delayed recall score or Free and Cued Selective Reminding Test immediate recall or delayed recall score greater than 1.5 Standard Deviation (SD) below norms or Selective Reminding Test immediate recall or delayed recall score greater than 1.5 SD below norms iii) no functional impairment consistent with dementia
Folstein Mini Mental State (MMSE) score ≥ 23 out of 30
Clinical Dementia Rating (CDR) of 0.5 (questionable dementia)
Availability of informant
Retains capacity to consent

You may not qualify if…

Medical contraindication to donepezil treatment or prior history of intolerability to donepezil treatment.
Medications with anticholinergic effects that have been shown to adversely impact cognition will not be permitted. Benzodiazepines in lorazepam equivalents less than or equal to 2 mg daily and narcotics will also not be permitted.
Meets criteria for dementia by Diagnostic and Statistical Manual IV (DSM-IV) or probable Alzheimer's disease by National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA)
Meets Diagnostic and Statistical Manual IV Text Revision (DSM IV TR) criteria for: (i)schizophrenia, schizoaffective disorder, other psychosis, or bipolar I disorder (ii)alcohol or substance dependence or abuse (current or within past 6 months)
Current untreated major depression or suicidality
Parkinson's disease, Lewy body disease, multiple sclerosis, central nervous system infection, Huntington's disease, amyotrophic lateral sclerosis, other major neurological disorder.
Mental Retardation
Cystic Fibrosis
Clinical stroke with residual neurological deficits. MRI findings of cerebrovascular disease (small infarcts, lacunes, periventricular disease) in the absence of clinical stroke with residual neurological deficits will not lead to exclusion.
Patients receiving cholinesterase inhibitors (donepezil, rivastigmine, galantamine) or memantine will be excluded. Patients already receiving one of these medications at screening who undergo a 2-week washout before starting all study procedures will not be excluded.
Acute, severe, unstable medical illness. For cancer, patients with active illness or metastases will be excluded, but past history of successfully treated cancer will not lead to exclusion.
Exclusion criterion for olfaction: history of anosmia due to any cause (e.g. traumatic or congenital) verified by UPSIT score of <11 out of 40; head trauma with loss of consciousness; nasal sinus disease, current upper respiratory infection; severe allergies to odors; current smoker > 1 pack daily.
Exclusion criteria for atropine nasal spray: presence of nasal deformity or disease that makes it difficult to administer the nasal spray reliably. A patient who cannot complete the atropine nasal spray procedure can still participate in the rest of the study.
Study 2
Inclusion Criteria:
Of either sex, age 55-95 years old
Diagnosis of probable Alzheimer's disease (NINCDS-ADRDA criteria) and the diagnosis of "Probable AD dementia: core clinical diagnosis with amnestic or nonamnestic initial presentation".
Folstein Mini Mental State (MMSE) score 18-27 out of 30
Availability of informant
Retains capacity to consent
Exclusion Criteria:
Medical contraindication to donepezil treatment or prior history of intolerability to donepezil treatment.
Medications with anticholinergic effects that have been shown to adversely impact cognition will not be permitted. Benzodiazepines in lorazepam equivalents less than or equal to 2 mg daily and narcotics will also not be permitted.
Meets DSM IV TR criteria for:(i)schizophrenia, schizoaffective disorder, other psychosis, or bipolar I disorder (ii)alcohol or substance dependence or abuse (current or within past 6 months)
Current untreated major depression or suicidality

Where it is running

New York State Psychiatric Institute — New York, New York, United States

Full record on ClinicalTrials.gov

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