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AlzRisk Paper Detail
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Reference: Hayden, 2006
Cohort: Cache County Study
Risk Factor: Diabetes Mellitus


Exposure Detail
"Individuals or their informants reported medical histories of CVRFs [CardioVascular Risk Factors] at the baseline and follow-up interviews. Participants were asked about a number of factors and history of events including hypertension, hypercholesterolemia, diabetes mellitus, stroke, CABG, and myocardial infarction. Interviewers recorded a positive history of each condition if the participant, or proxy informant, indicated he/she was ever told about the condition by a doctor or nurse and he/she received treatment for it. If the participant did not specify a doctor’s diagnosis or treatment, a negative history was recorded. A negative history was also recorded if the participant reported no history of the condition or event. In the event that the status was unknown, the item was recorded as missing. Information on participants’ current use of antihypertensives, lipid lowering agents, and diabetes medications gained from a medicine chest inventory taken at the time of the interview was also considered."

Ethnicity Detail
Not reported in this paper. All participants were residents of Cache County, Utah, USA. According to a description of the cohort, nearly all members (99%) of the Cache County Study cohort are white.

Screening and Diagnosis Detail
Screening Method:
"Modified" 3MSE"Modified" Modified Mini-Mental State Examination (Tschantz 2002)
DQDementia Questionnaire (Silverman 1986)
IQ-CODEInformant Questionnaire for Cognitive Decline in the Elderly (Jorm 1989)

AD Diagnosis:
DSM IIIR Diagnostic and Statistical Manual III-Revised
NINCDS ADRDA National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association Criteria (McKhann 1984)

Total dementia definition: AD or vascular dementia (VaD), where VaD was diagnosed via National Institute for Neurologic Disorders and Stroke-Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS-AIREN; Roman 1993).

"Participants’ cognitive status was assessed via a multistage screening procedure at follow-up, approximately 3.2 years (range= 2-5y, standard deviation= 0.44) after the baseline assessment. A modified version 22 of the Modified Mini-Mental State Exam (3MS)23 was administered either at the participants’ home or in the nursing home. The Informant Questionnaire for Cognitive Decline in the Elderly (IQCODE)24 was administered to a proxy informant, that is, spouse or next of kin, in the event that participants were unable to complete the 3MS. Individuals who scored beyond predetermined cut-points were referred for further assessment with the dementia questionnaire (DQ)25, which was administered by phone to a proxy informant. At the follow-up evaluation, all those scoring below 87 on the 3MS, our predetermined cut-point, 21 all those over age 80 scoring below 84 on the 3MS, and all those scoring above the recommended cut-point of 3.27 on the IQCODE were referred for further assessment with the DQ. A subsample of participants, including all participants aged 90 or older, were also referred for DQ. If participants scored >4 on the DQ at baseline20 or >3 at follow-up21or were part of the designated subsample, they were referred for a full clinical assessment. "A psychometrician and a research nurse conducted assessments at the participants’ home or nursing home, in the presence of an informant. The nurse recorded the participant’s history of cognitive symptoms if any, medical history, current medications used, and blood pressure, and administered a standardized neurologic examination and the Neuropsychiatric Inventory 26 The Dementia Severity Rating Scale27 was used to assess cognitive and functional impairment. A family history and a 7-minute videotape of the participants were taken, and a battery of neuropsychologic tests was administered.28 If dementia was suspected, further information was gathered from participants via laboratory tests, that is, blood count, routine chemistries, serum B12, folate, thyroid function test, urinalysis, and standardized magnetic resonance imaging, or in few cases via computed tomography. Geriatric psychiatrists, blind to the participant’s working diagnosis, examined individuals with possible dementia at their place of residence. Clinical history and Neuropsychiatric Inventory results were reviewed with collateral informants. The assignment of initial diagnoses occurred at consensus conferences attended by the staff who conducted the evaluations and a geriatric psychiatrist (D.C.S., J.C.S.B., or M.S.). Final best estimate diagnoses were assigned by consensus at conferences with geriatric psychiatrists, a board certified neurologist, a senior neuropsychologist, and a cognitive neuroscientist in attendance. Diagnoses were made according to the Diagnostic and Statistical Manual of Mental Disorders, 3rd ed. revised (DSM-III-R) criteria 29 using all available information. The National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association criteria30 was used for AD diagnoses. VaD was identified with the National Institute of Neurological Disorders and Stroke and Association Internationale pour la Recherche et l’Enseignement en Neurosciences 31 criteria. The Clinical Dementia Rating Scale 32 was used to assess dementia severity. The age at onset of dementia was recorded as the estimated year in which participants unambiguously met DSM-III-R criteria for dementia."

Covariates & Analysis Detail
Analysis Type:
Discrete-time survival modeling

"Discrete-time survival models 35 were used to estimate the relationship between each CVRF and dementia after adjustment for potential confounders. This method considers time in discrete intervals, in this case years, which is appropriate, given the exact time of onset of dementia and CVRFs are not known. Using this method, each year was considered a discrete time interval. Thus, each subject contributed to the analysis one person-year of observation for each year from the age at which the subject entered the study until either his/her onset of dementia or end of the follow-up period."

AD Covariates:
Aage
Eeducation
Ggender
APOE4APOE e4 genotype
CABGcoronary artery bypass graft
CHDcoronary heart disease
HChigh cholesterol
HTNhypertension
OBoverweight/obesity
SHstroke history

TD Covariates:
Aage
Eeducation
Ggender
APOE4APOE e4 genotype
CABGcoronary artery bypass graft
CHDcoronary heart disease
HChigh cholesterol
HTNhypertension
OBoverweight/obesity
SHstroke history