--- title: Olfactory Deficits and Donepezil Treatment in Cognitively Impaired Elderly nct_id: NCT01951118 overall_status: COMPLETED phase: PHASE4 sponsor: New York State Psychiatric Institute study_type: INTERVENTIONAL primary_condition: Alzheimer Disease countries: United States canonical_url: "https://parkinsonspathways.com/agent/trials/NCT01951118.md" clinicaltrials_gov: "https://clinicaltrials.gov/study/NCT01951118" ct_last_update_post_date: 2020-07-13 last_seen_at: "2026-05-12T06:05:37.585Z" source: ClinicalTrials.gov (mirrored, no enrichment) --- # Olfactory Deficits and Donepezil Treatment in Cognitively Impaired Elderly **NCT ID:** [NCT01951118](https://clinicaltrials.gov/study/NCT01951118) ## Key Facts - **Status:** COMPLETED - **Phase:** PHASE4 - **Study Type:** INTERVENTIONAL - **Target Enrollment:** 121 - **Lead Sponsor:** New York State Psychiatric Institute - **Collaborators:** National Institutes of Health (NIH), National Institute on Aging (NIA) - **Conditions:** Alzheimer Disease, Mild Cognitive Impairment, Delirium, Dementia, Amnestic, Cognitive Disorders - **Start Date:** 2013-10 - **Completion Date:** 2019-05 - **CT.gov Last Update:** 2020-07-13 ## Brief Summary 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. ## Detailed Description In this clinical trial, the investigators will evaluate, treat and follow two broad samples of adult patients at New York State Psychiatric Institute/Columbia University Medical Center. Study 1 will include 70 patients with amnestic Mild Cognitive Impairment (MCI). Study 2 will include 100 patients with probable Alzheimer's Disease (AD). Recruitment will be from clinics and/or advertisements. In the protocol, all 170 patients will receive baseline memory and olfactory assessments and are treated with donepezil. Patients will be followed for a total of 1 year. During this time, patients will be monitored closely by the study physician and will receive memory and olfactory assessments at weeks 0, 8, 26, and 52. In addition, an olfactory challenge test will be done at baseline. This project will be of value in the selection of patients with MCI and AD for treatment based on the evaluation of olfaction tests to predict response to donepezil. Since mild cognitive impairment is widespread and Alzheimer's disease represents a major public health problem, this study has considerable public purpose and significance. ## Eligibility - **Minimum age:** 55 Years - **Maximum age:** 95 Years - **Sex:** ALL - **Healthy Volunteers:** No ``` Study 1 Inclusion Criteria: * 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 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 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 * 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. ``` ## Arms - **Donepezil Treatment & Atropine Challenge** (EXPERIMENTAL) — Atropine nasal spray is administered at baseline for the atropine challenge which involves administration of the 40-item UPSIT immediately before and 45 minutes after atropine administration. Immediately after the atropine challenge, donepezil treatment is started and continues for 52 weeks. ## Interventions - **Donepezil** (DRUG) — Donepezil 5mg will be given for 4 weeks and if tolerated, the dose will be increased to 10 mg per day. The dose range of 5 to 10 mg of donepezil per day will be continued for the study duration, and this is the recommended dose for donepezil in the treatment of mild to moderate Alzheimer's disease. For patients who do not tolerate donepezil or have a history of intolerance to donepezil or cannot take donepezil for other reasons, treatment with other cholinesterase inhibitors (galantamine or rivastigmine) is permitted at any stage of the protocol. Data will be analyzed in two ways: for donepezil alone, and for any cholinesterase inhibitor (donepezil or rivastigmine or galantamine) as the intervention. ## Primary Outcomes - **Change Over Time in Selective Reminding Test (SRT) Scores** _(time frame: Week 0, Week 8, Week 26, Week 52)_ — The Selective Reminding Test (SRT) is a 12-item test of verbal learning and memory. To administer, the researcher will read aloud a list of 12 words. The participant repeats each word aloud to ensure that the word was heard correctly. Immediately following the reading of all 12 words, the participant is asked to recall as many words as possible within the one minute time limit. The participant is then reminded of the words they did not say and asked to recall the list again. This process is repeated for 6 trials. The total immediate recall is the total number of words recalled by the participant from all 6 trials. This is the number that is reported. Lower scores indicate fewer words recalled and a poorer performance. ## Secondary Outcomes - **Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog)** _(time frame: Week 0, Week 8, Week 26, Week 52)_ - **Clinician's Interview Based Impression (CIBIC-plus)** _(time frame: Week 8, Week 26, Week 52)_ - **Pfeffer Functional Activities Questionnaire (FAQ)** _(time frame: Week 0, Week 8, Week 26, Week 52)_ - **Measurement of Everyday Cognition (Ecog)** _(time frame: Week 0, Week 8, Week 26, Week 52)_ ## Locations (1) - New York State Psychiatric Institute, New York, New York, United States ## Recent Field Changes (last 30 days) - `eligibility.sex` — added _(2026-05-12)_ - `status.overallStatus` — added _(2026-05-12)_ - `status.primaryCompletionDate` — added _(2026-05-12)_ - `status.completionDate` — added _(2026-05-12)_ - `status.lastUpdatePostDate` — added _(2026-05-12)_ - `design.phases` — added _(2026-05-12)_ - `design.enrollmentCount` — added _(2026-05-12)_ - `eligibility.criteria` — added _(2026-05-12)_ - `eligibility.minAge` — added _(2026-05-12)_ - `eligibility.maxAge` — added _(2026-05-12)_ - `outcomes.primary` — added _(2026-05-12)_ - `outcomes.secondary` — added _(2026-05-12)_ - `armsInterventions.arms` — added _(2026-05-12)_ - `armsInterventions.interventions` — added _(2026-05-12)_ - `sponsor.lead` — added _(2026-05-12)_ - `sponsor.collaborators` — added _(2026-05-12)_ - `results.hasResults` — added _(2026-05-12)_ - `locations.new york state psychiatric institute|new york|new york|united states` — added _(2026-05-12)_ --- *Canonical: https://parkinsonspathways.com/agent/trials/NCT01951118.md* *Source data (authoritative): https://clinicaltrials.gov/study/NCT01951118* *This page is a raw mirror with no AI summary, no editorial enrichment, and no Parkinson's-specific filtering.*