Working Group on Study Design - Inclusion/Exclusion Criteria Table

Item	NL	MCI	AD
Memory Complaints		Memory complaints and memory difficulties that are verified by an informant.
Memory Function	Normal memory function documented by scoring at specific cutoffs on the Logical Memory II subscale (delayed Paragraph Recall) from the Wechsler Memory Scaled - Revised (the maximum score is 25): a) more than or equal to 10 for 16 or more years of education b) more than or equal to 6 for 8-15 years of education c) more than or equal to 4 for 0-7 years of education.	Abnormal memory function documented by scoring below the education adjusted cutoff on the Logical Memory II subscale (Delayed Paragraph Recall) from the Wechsler Memory Scale – Revised (the maximum score is 25): a) less than or equal to 8 for 16 or more years of education, b) less than or equal to 4 for 8-15 years of education, c ) less than or equal to 2 for 0-7 years of education. (See the paragraph on MCI criteria in the RFA, Research Objectives section)
MMSE	Mini-Mental State Exam score between 24 and 30 (inclusive) (Exceptions may be made for subjects with less than 8 years of education at the discretion of the project director).	Mini-Mental State Exam score between 24 and 30 (inclusive) (Exceptions may be made for subjects with less than 8 years of education at the discretion of the project director).	MMSE between 18 and 26, inclusive.
CDR	Clinical Dementia Rating = 0.  Memory Box score must be 0.	Clinical Dementia Rating = 0.5.  Memory Box score must be at least 0.5.	Clinical Dementia Rating = 0.5, 1.0 or 2.0.
General Cognition	Cognitively normal, based on an absence of significant impairment in cognitive functions or activities of daily living.	General cognition and functional performance sufficiently preserved such that a diagnosis of Alzheimer's disease cannot be made by the site physician at the time of the screening visit.	NINCDS/ADRDA criteria for probable AD.
Hachinski	Modified Hachinski score of less than or equal to 4.	Modified Hachinski score of less than or equal to 4.	Modified Hachinski score of less than or equal to 4.
Age	Age between 55 and 90 (inclusive).	Age between 55 and 90 (inclusive).	Age between 55 and 90 (inclusive).
Stability of Permitted medications	Permitted medications stable for at least 4 weeks prior to screening.  In particular: a) Subjects may take stable doses of antidepressants lacking significant anticholinergic side effects (if they are not currently depressed and do not have a history of major depression within the past 2 years) b) Estrogen replacement therapy is discouraged c) Gingko biloba is permissible, but discouraged d) Washout from psychoactive medication (e.g., excluded anti-depressants, neuroleptics, chronic anxiolytics or sedative hypnotics, etc.) for at least 4 weeks prior to screening.	Permitted medications stable for at least 4 weeks prior to screening.  In particular: a) Subjects may take stable doses of antidepressants lacking significant anticholinergic side effects (if they are not currently depressed) b) Estrogen replacement therapy is discouraged c) Gingko biloba is permissible, but discouraged d) Washout from psychoactive medication (e.g., excluded anti-depressants, neuroleptics, chronic anxiolytics or sedative hypnotics, etc.) for at least 4 weeks prior to screening. e) Cholinesterase inhibitors are allowable.	Permitted medications stable for at least 4 weeks prior to screening.  In particular: a) Subjects may take stable doses of antidepressants lacking significant anticholinergic side effects (if they are not currently depressed and do not have a history of major depression within the past 2 years) b) Estrogen replacement therapy is discouraged c) Gingko biloba is permissible, but discouraged d) Washout from psychoactive medication (e.g., excluded anti-depressants, neuroleptics, chronic anxiolytics or sedative hypnotics, etc.) for at least 4 weeks prior to screening. e) Cholinesterase inhibitors are allowable.
Hamilton	Hamilton Depression rating scale score of less than or equal to 12 on the 17-item scale. (With later discussion, inclusion of subjects with depression, as long as there's a reasonable chance they can come for follow-up visits and complete testing, is encouraged)	Hamilton Depression rating scale score of less than or equal to 12 on the 17-item scale.(With later discussion, inclusion of subjects with depression, as long as there's a reasonable chance they can come for follow-up visits and complete testing, is encouraged)	Hamilton Depression rating scale score of less than or equal to 12 on the 17-item scale.(With later discussion, inclusion of subjects with depression, as long as there's a reasonable chance they can come for follow-up visits and complete testing, is encouraged)
Informant/caregiver	Informant is available who has frequent contact with the subject (e.g. an average of 10 hours per week or more),  and accompany the subject to all clinic visits for the duration of the protocol.	Informant is available who has frequent contact with the subject (e.g. an average of 10 hours per week or more),  and accompany the subject to all clinic visits for the duration of the protocol.	Caregiver/informant to accompany patient to all scheduled visits.
Visual and auditory acuity	Adequate visual and auditory acuity to allow neuropsychological testing.	Adequate visual and auditory acuity to allow neuropsychological testing.	Adequate visual and auditory acuity able to complete baseline assessments.
General Health	Good general health with no additional diseases expected to interfere with the study.	Good general health with no additional diseases expected to interfere with the study.	Good general health with no additional diseases expected to interfere with the study.
Pregnancy/Childbearing Potential	Subject is not pregnant, lactating, or of childbearing potential (i.e. women must be two years post-menopausal or surgically sterile).	Subject is not pregnant, lactating, or of childbearing potential (i.e. women must be two years post-menopausal or surgically sterile).	Subject is not pregnant, lactating, or of childbearing potential (i.e. women must be two years post-menopausal or surgically sterile).
Testability	Willing and able to complete all baseline assessments. Willing and able to participate in a 3-year protocol.	Willing and able to complete all baseline assessments. Willing and able to participate in a 3-year protocol.	Willing and able to complete all baseline assessments. Willing and able to participate in a 2-year protocol.
Commitment to neuroimaging and providing study samples	Willing to undergo neuroimaging (MRI, PET) and provide DNA  for ApoE assessments and banking as well as plasma samples at protocol specified time points.	Willing to undergo neuroimaging (MRI, PET) and provide DNA  for ApoE assessments and banking as well as plasma samples at protocol specified time points.	Willing to undergo neuroimaging (MRI, PET) and provide DNA  for ApoE assessments and banking as well as plasma samples at protocol specified time points.
Commitment to provide CSF samples	Willing to provide CSF for biomarker studies at protocol specified time points (optional).	Willing to provide CSF for biomarker studies at protocol specified time points (optional).	Willing to provide CSF for biomarker studies at protocol specified time points (optional).
Education	Completed 6 grades of education (or had a good work history sufficient to exclude mental retardation).	Completed 6 grades of education (or had a good work history sufficient to exclude mental retardation).	Completed 6 grades of education (or had a good work history sufficient to exclude mental retardation).
Language	Fluent in English or Spanish.	Fluent in English or Spanish.	Fluent in English or Spanish.
EXCLUSION CRITERIA
Significant neurologic disease	Any significant neurologic disease, such as Parkinson's disease, multi-infarct dementia, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma followed by persistent neurologic defaults or known structural brain abnormalities.	Any significant neurologic disease other than suspected incipient Alzheimer's disease, such as Parkinson's disease, multi-infarct dementia, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma followed by persistent neurologic defaults or known structural brain abnormalities.	Any significant neurologic disease other  than Alzheimer's disease including Parkinson's disease, multi-infarct dementia, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma followed by persistent neurologic defaults or known structural brain abnormalities.
Neuroimaging	Screening/baseline MRI scans with evidence of infection, infarction, or other focal lesions. Subjects with multiple lacunes or lacunes in a critical memory structure are excluded.	Screening/baseline MRI scans with evidence of infection, infarction, or other focal lesions. Subjects with multiple lacunes or lacunes in a critical memory structure are excluded.	Screening/baseline MRI scans with evidence of infection, infarction, or other focal lesions. Subjects with multiple lacunes or lacunes in a critical memory structure are excluded.
MRI exclusions	Presence of  pacemakers, aneurysm clips, artificial heart valves, ear implants, metal fragments or foreign objects in the eyes, skin or body.	Presence of  pacemakers, aneurysm clips, artificial heart valves, ear implants, metal fragments or foreign objects in the eyes, skin or body.	Presence of  pacemakers, aneurysm clips, artificial heart valves, ear implants, metal fragments or foreign objects in the eyes, skin or body.
Psychiatric disorders/psychotic features	. History of schizophrenia (DSM IV criteria).	Psychotic features, agitation or behavioral problems within the last 3 months which could lead to difficulty complying with the protocol. History of schizophrenia (DSM IV criteria).	Psychotic features, agitation or behavioral problems within the last 3 months which could lead to difficulty complying with the protocol. History of schizophrenia (DSM IV criteria).
Alcohol abuse	History of alcohol or substance abuse or dependence within the past 2 years (DSM IV criteria).	History of alcohol or substance abuse or dependence within the past 2 years (DSM IV criteria).	History of alcohol or substance abuse or dependence within the past 2 years (DSM IV criteria).
Significant medical illness	Any significant systemic illness or unstable medical condition which could lead to difficulty complying with the protocol.	Any significant systemic illness or unstable medical condition which could lead to difficulty complying with the protocol.	Any significant systemic illness or unstable medical condition which could lead to difficulty complying with the protocol.
Clinically significant laboratory abnormalities	Clinically significant abnormalities in B12, RPR, or TFTs that might interfere with the study.	Clinically significant abnormalities in B12, RPR, or TFTs that might interfere with the study.	Clinically significant abnormalities in B12, RPR, or TFTs that might interfere with the study.
Residence	Residence in skilled nursing facility.	Residence in skilled nursing facility.	Residence in skilled nursing facility.
Concomitant medications	Current use of specific psychoactive medications  (e.g., certain antidepressants, neuroleptics, chronic anxiolytics or sedative hypnotics, etc.). Current use of warfarin.	Current use of specific psychoactive medications  (e.g., certain antidepressants, neuroleptics, chronic anxiolytics or sedative hypnotics, etc.). Current use of warfarin.	Current use of specific psychoactive medications  (e.g., certain antidepressants, neuroleptics, chronic anxiolytics or sedative hypnotics, etc.). Current use of warfarin.
Investigational agents	Prohibited at entry.	Prohibited at entry.	Prohibited at entry.
Exceptions by project director	*Exceptions to these guidelines may be considered on a case-by-case basis at the discretion of the project director.	*Exceptions to these guidelines may be considered on a case-by-case basis at the discretion of the project director.	*Exceptions to these guidelines may be considered on a case-by-case basis at the discretion of the project director.

Page last updated Feb 16, 2008