The analysis cohort included 702 subjects. presents the demographic information for the whole cohort and by initial diagnosis [mild cognitive impairment (MCI) or AD]. The sample contained more females (65%) than males (35%). Eighty percent of the subjects were white and 20% were African American. About 50% of the subjects had 8-12 years of education. The ApoE allele frequencies were: e2=5%, e3=58%, e4=38%. These frequencies are very close to what would be expected in a sample of cases with the observed composition by race.17
The age at symptom onset ranged from 44 to 95 years with an average of 72 years. The mean of MMS at initial visit was 18. There were no significant differences of sex, race, education, ApoE genotype between subjects who had only one visit (n=247) and subjects who had at least two visits (n=455). The mean age of onset among subjects with only one visit (mean=73, SD=8.3) was significantly higher (p= 0.004) than that among subjects with at least two visits (mean=71, SD=8.4).
Mean (±S.D., range) Demographic Characteristics of Participants#
displays the characteristics of informants. About 87% of the informants were either spouse or child. Seventy-six percent of the informants had contact with the patients five or more days per week.
Characteristics of Informants
The rates of change in DSRS during 0-2, 2-5, and 5-7 years were estimated and no significant differences among the three rates were found (p>0.73). The estimated annual rate of change difference between 0-2 and 2-5 years is -0.09 (95% confidence interval [CI]: -1.04 - 0.86). The estimated annual rate of change difference between 2-5 and 5-7 years is -0.41 (95% CI: -2.76 - 1.94). The estimated annual rate of change difference between 0-2 and 5-7 years is -0.50 (95% CI: -2.79 - 1.79). These confidence intervals all contained 0 and were not wide clinically. Thus, an overall rate of change can be generated. The results indicate that the DSRS increased by an average of 4.48 (95% CI: 4.14 - 4.82) points per year throughout the observation period. Accounting for the random effects, the 95% prediction interval for this annual rate of decline is 2.03 – 6.93. Because some DSRS values were missing due to the truncation of score 40, we performed a sensitivity analysis to examine if our conclusion changed when we didn't truncate the DSRS values. We found that there were no significant differences of the three rates of decline corresponding to 0-2, 2-5, and 5-7 years (p > 0.42) when we didn't truncate DSRS values. The overall annual rate of change for the entire period is 5.05 (95% CI: 4.67 – 5.42) in this situation. Thus, the annual expected rates of declines were similar when truncating or not truncating at score 40 of DSRS.
In contrast, the MMS score declined by an average of 2.15 (95% CI: 1.85 - 2.46) points per year during the first two years of observation and then accelerated to an annual decline of 3.83 (95% CI: 3.28 - 4.38) points per year during the subsequent three years before slowing to an average decline of 1.63 (95% CI: 0.21 - 3.05) points per year during the last two years of observation. The annual rates of MMS change in the three time intervals were significantly different (p< 0.0001 when comparing the annual rate in the first two years to the annual rate in years 2-5; p=0.0107 when comparing the annual rate in years 2-5 to the annual rate in years 5-7).
displays the predicted DSRS and MMS values from the piece-wise linear mixed-effect model which produced three estimated rates corresponding to the three time periods (0-2, 2-5, 5-7 years). The DSRS changed almost linearly throughout the study period, while the MMS changed in a non-linear fashion.
Predicted DSRS and MMS Values over Time from the Piece-wise Mixed-effect Models*
The annual rates of change in both the DSRS and the MMS differed significantly by age at symptom onset. The annual rate of change in the DSRS slowed by 0.045 points for each one-year increase in the age at onset (p=0.03). Therefore, the estimated annual rate of change dropped from about 4.47 points for age at onset of 70 years to 4.02 points for age at onset of 80 years. The annual rate of change in the MMS also slowed by 0.076 points for each one-year increase in the age at onset (p<0.0001).
We performed the mixed-effect analysis of DSRS and MMS by examining the interactions between duration of follow-up time and disease severity at baseline [MCI, mild AD (MMS >=18), moderate AD (MMS 11-17, inclusive), severe AD (MMS <=10)]. We found that the interaction term was not significant (p=0.12 for DSRS and p=0.11 for MMS) and thus dementia severity at baseline did not significantly influence the annual rate of decline for both DSRS and MMS. For DSRS, this implies that we can expect a patient to decline at a rate of about 4.48 points in a 12 month period no matter whether they started with MCI or probable AD.
There were no significant differences at the 0.05 level in the annual rate of change for the DSRS or the MMS by sex, education, ApoE genotype, race or occupation.
There were 196 patients for whom there were two DSRS scores collected from the same respondent within three months of each other. The mean interval between scores was 43 days. The mean score on the first test was 18.69 compared to 18.65 for the second. The mean absolute difference between the two scores was 3.06 with a maximum of 12 points. The reliability coefficient for the total score was 0.95. Kappa statistics for the individual items ranged from 0.54 to 0.71. All were significantly different from 0 at the 0.05 level. Spearman correlation coefficients for the individual items ranged from 0.66 to 0.82, and all were significantly different from 0 at the 0.05 level.