Observational Study of Cognitive Outcomes for Subjects Who Have Had Prior PET Amyloid Imaging With Florbetapir F 18 (18F-AV-45)

Phase 2

Completed

Conditions: Alzheimer's Disease
Mild Cognitive Impairment

Registration Number: NCT00857506

Lead Sponsor: Avid Radiopharmaceuticals

Brief Summary: The primary objective of this protocol is to determine if brain amyloid imaged with florbetapir F 18 (18F-AV-45) PET scans is predictive of progressive cognitive impairment during the subsequent 36 months for groups of: normal controls, mild cognitive impairment and Alzheimer's disease.

Hypothesis 1: The probability a subject will experience progressive cognitive impairment within 36 months of imaging will be greater in subjects whose 18F-AV-45 PET scan was rated amyloid positive compared to subjects whose PET scan was rated amyloid negative.

The secondary objective is to determine the stability, over 36 months of a clinical diagnosis, of AD in patients with an amyloid positive 18F-AV-45 PET.

Hypothesis 2: The diagnosis of AD will remain unchanged in patients whose PET scan were rated as amyloid positive.

Detailed Description: Study AV-45-A11 is designed to determine if brain amyloid aggregation imaged on 18F-AV-45 PET scans is predictive of progression of cognitive impairment during the subsequent 36 months. Approximately 180 subjects enrolled in a prior clinical study (AV-45-A05\[NCT00702143\]) will be offered an opportunity to be studied under this protocol. The initial visit will occur as soon as possible following the AV-45-A05(NCT00702143) imaging day. Subjects who qualify for the study and their caregiver/partners will be contacted approximately 6,12,18,24 and 36 months after PET imaging in study AV-45-A05(NCT00702143), and will undergo a standardized functional and psychometric evaluation.

NOTE: This study is a clinical follow-up of subjects previously enrolled in trial 18F-AV-45-A05(NCT00702143). No new patients are being enrolled in this trial.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 152

Inclusion Criteria

All subjects who enrolled in study AV-45-A05(NCT00702143), received 18F-AV-45, and completed a PET scan will be eligible to enroll in this trial.

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Change in ADAS-Cog for MCI Subjects	Baseline and 36 months	The primary analysis was the comparison in the magnitude of change from baseline in Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-Cog) between Aβ+ and Aβ- subjects in the Mild Cognitive Impairment (MCI) population at 36 months adjusting for baseline test score and age at informed consent. ADAS-Cog scores (range 0-70) indicate performance on a series of 11 cognitive tasks where 0 indicates the highest level of cognitive performance and 70 indicates the lowest level of cognitive performance. Change in ADAS-Cog scores were calculated by subtracting the baseline score from the 36 month score (last observation carried forward \[LOCF\]). A change in ADAS-Cog greater than 0 indicates a deterioration in cognitive performance whereas a change in ADAS-Cog less than 0 indicates improved cognitive performance.

Secondary Outcome Measures

Name	Time	Method
Change in ADAS-Cog in CN and AD Subjects	Baseline and 36 months	This analysis compared the magnitude of change from baseline in ADAS cognitive subscale (ADAS-Cog) scores between Aβ+ and Aβ- subjects in the CN and AD populations at 36 months adjusting for baseline test score and age at informed consent. ADAS-Cog scores (range 0-70) indicate performance on a series of 11 cognitive tasks where 0 indicates the highest level of cognitive performance and 70 indicates the lowest level of cognitive performance. Change in ADAS-Cog scores were calculated by subtracting the baseline score from the 36 month score (LOCF). A change in ADAS-Cog greater than 0 indicates a deterioration in cognitive performance whereas a change in ADAS-Cog less than 0 indicates improved cognitive performance.
Cognitive Decline in CN and AD Subjects	Baseline and 36 months	The key secondary analyses compared the number of Aβ+ and Aβ- subjects in the CN and AD populations with clinically significant deterioration in ADAS-Cog (≥4) and CDR global score (≥0.5). ADAS-Cog scores (range 0-70) indicate performance on a series of cognitive tasks where 0 indicates the highest level of cognitive performance and 70 indicates the lowest level of cognitive performance. CDR scores (range 0-3) quantify the severity of the symptoms of dementia where 0 indicates no cognitive impairment and 3 indicates severe dementia. Changes in ADAS-Cog and CDR scores were calculated by subtracting the baseline score from the 36 month score (LOCF).
Covariate Adjusted Psychometric Score Change	Baseline and 36 months	Change from baseline by diagnostic group in covariate-adjusted psychometric assessment scores at month 36 (LOCF). Assessments included Digit Symbol Substitution (DSS), Clinical Dementia Rating Sum of Boxes (CDR-SOB), Mini-Mental State Examination (MMSE), Wechsler Logical Memory Scale (WLMS) delayed and immediate recall, Category Verbal Fluency (CVF) animals and vegetables, Alzheimer's Disease Clinical Studies Consortium Activities of Daily Living (ADCS ADL) and Geriatric Depression Scale (GDS). The ranges for these scales are as follows: DSS (0-93), CDR-SOB (0-18), MMSE (0-30), WLMS delayed and immediate recall (0-25), CVF animals and vegetables (0-total number of relevant items named in 60 seconds), ADCS ADL (0-78) and GDS (0-15). For all scales except CDR-SOB and GDS a higher score indicates greater cognitive function. For CDR-SOB and GDS a higher score indicates increased dementia or depression, respectively.
Correlation of Change in ADAS-Cog and SUVR	Baseline and 36 months	Correlation between change from baseline to 36 month ADAS-Cog score and baseline global average SUVR by diagnostic group is provided below. ADAS-Cog scores (range 0-70) indicate performance on a series of 11 cognitive tasks where 0 indicates the highest level of cognitive performance and 70 indicates the lowest level of cognitive performance. Change in ADAS-Cog scores were calculated by subtracting the baseline score from the 36 month score (LOCF). A change in ADAS-Cog greater than 0 indicates a deterioration in cognitive performance whereas a change in ADAS-Cog less than 0 indicates improved cognitive performance. Standard Uptake Value Ratio (SUVR) is the ratio of tracer uptake in the cortex and cerebellum. SUVR values higher than 1 indicate greater amyloid burden in the cortex as compared to the cerebellum whereas scores less than 1 indicate the opposite.
Cognitive Decline in MCI Subjects	Baseline and 36 months	The key secondary analyses compared the number of Aβ+ and Aβ- subjects in the MCI population with clinically significant deterioration in ADAS-Cog (≥4) and Clinical Dementia Rating (CDR) global score (≥0.5) and conversion in diagnosis from MCI at baseline to AD or Cognitively Normal (CN) at 36 months. ADAS-Cog scores (range 0-70) indicate performance on a series of 11 cognitive tasks where 0 indicates the highest level of cognitive performance and 70 indicates the lowest level of cognitive performance. CDR scores (range 0-3) quantify the severity of the symptoms of dementia where 0 indicates no cognitive impairment and 3 indicates severe dementia. Changes in ADAS-Cog and CDR scores were calculated by subtracting the baseline score from the 36 month score (LOCF).