There were 480 (13.3%) cases of incident dementia over an approximate 5.7 years of follow-up among 3,375 participants without dementia at the time of MRI in 1991 to 1994. The pre-MRI review classified 330 (69%) cases as AD, 52 (11%) as VaD, 76 (16%) as both VaD and AD, and 22 (5%) as Parkinson disease and other dementia.
After reviewing the MRI, the adjudicators were then given access to the MRI to classify the specific types of dementia, including both the pre-MRI and MRI data. The comparison of ADDTC-diagnosed VaD and the pre-MRI classification of the type of dementia for incident cases is shown in .
Comparison of modified ADDTC criteria for VaD and pre-MRI classification (clinical) incident cases
The incidence of VaD increased dramatically with age (). Rates were higher for blacks than for whites. There was not a significant sex difference.
Incidence of vascular dementia (by Alzheimer’s Disease Diagnostic and Treatment Centers criteria) by age, sex, and race. PYs = person-years.
The relative risk of VaD (compared with subjects) in the presence of an incident stroke post-MRI was high: 4.5 (95% CI, 3.1 to 6.5; see table E-2). Among the 37 patients with VaD with an incident stroke post-MRI, 23 (62%) were diagnosed within the year of the stroke, 11 (30%) in the first year after the stroke, and three (8%) more than 1 year after. A history of coronary artery disease before the MRI was noted in 29% of patients classified as having VaD (HR: 1.4; 95% CI, 1.1 to 1.9; age, race, and sex adjusted; see table E-2). Similarly, 10% had a history of bypass surgery (HR: 2.6; 95% CI, 1.7 to 4.1). There was no association with a history of coronary angioplasty and risk of VaD (see table E-2).
Age-adjusted HRs for MRI variables associated with VaD were ventricular atrophy >5 + 2.1 (95% CI, 1.5 to 2.8); for WMG, 3 + 3.9 (95% CI, 2.9 to 5.2), and for one or more infarcts ≥3 mm on MRI, 4.8 (95% CI, 3.6 to 6.4). The incidence of VaD was linearly related to the number of infarcts identified on MRI, a higher WMG, and ventricular size ().
Incidence of vascular dementia by baseline MRI findings, HRs, and 95% CIs adjusted for age, race, and sex: 213 vascular dementias and 2,318 normals
Among 177 patients with incident VaD with no clinical history of stroke before the MRI, there were 118 with the largest infarct on the MRI ≥3 mm, of which 11% were in the cortex, 6% were in the cerebellum, 71% were in the basal ganglion, 5% were classified as located in the deep cerebellum, and 7% were classified as in the deep white matter. The distribution for the 530 subjects with at least one infarct on MRI was similar, with the majority (73% or 395) in the basal ganglion.
The risk factors for VaD with or without AD by the NINCDS-ADRDA classification of AD after review of MRI (see table E-3). There were 61 subjects who were classified as having VaD by modified ADDTC and not AD by ADRDA criteria and 245 who were classified as having AD by ADRDA criteria and not VaD by modified ADDTC criteria. The patients who were classified as having VaD and not AD had a high percentage (56% [34 of 61]) of either prevalent stroke at the time of MRI or incident stroke as well as high WMG (p = 0.001), a greater number of MRI infarcts (p = 0.001), a history of hypertension (p = 0.003), and any subclinical CVD (p = 0.005) compared with those classified as having AD only (p = 0.001). Those (224 subjects) with AD without vascular components have a higher prevalence of ApoE4 (40%) compared with subjects with VaD (p = 0.001). There was also a higher percentage of women with AD but not VaD, 66% compared with 46% for VaD (p = 0.005) and 59% (p = 0.03) among normals.
We then compared risk factors for VaD only, VaD and AD, and AD only () by Cox models comparing subjects. Black race, high WMG, MRI infarcts, stroke before the MRI, hypertension, and history of angina pectoris were predictors of VaD. ApoE4 was an independent predictor of both AD with and without VaD. Diabetes was also a significant risk factor for AD alone and similarly related to AD with VaD. Risk factors for cases classified as VaD with AD were black race, high WMG, and the presence of infarcts on MRI. Female sex was a significant risk factor only for AD without a vascular component. Age, lower 3MSE score, and history of angina pectoris were significantly related to all three types of dementia (see ). Lower education was not a significant risk factor after including the 3MSE score in the Cox models.
Cox models comparing each of the three incident dementia groups defined by combinations of ADDTC VaD and NINCDSADRDA AD with normals
The risk factors for VaD classified before or after review of MRI were similar. The pre-MRI review was less biased because MRI variables are part of post-MRI criteria for VaD (see table E-4).