Blood lead, bone lead, and adult cognitive function 412–515 of whom took different tests twice approximately 3.5 years apart) (Weisskopf et al. 2007). Cross-sectional analyses in the original report found that increased blood lead levels across a relatively low range of levels [mean ± SD = 5.5 ± 3.5 µg/dL) were a stronger predictor, compared with tibia or patella lead levels, of poorer performance on tests of speed, verbal memory, vocabulary, and spatial copying skills. However, this was not confirmed in the larger, cross-sectional analysis, except possibly for scores on a vocab- ulary test (Weisskopf et al. 2007). Conversely, in longitudinal analyses, the larger study found more decline over time on almost all cognitive tests associated with both higher patella and higher tibia bone lead levels, with the associations reaching statistical signifi- cance for pattern comparison and spatial copying skills. An earlier, similar longitudinal analysis by Weisskopf et al. (2004) in this same population reported that patella lead levels were significantly associated with a decline in Mini-Mental State Examination (MMSE; Folstein et al. 1975) score over time. A slightly smaller association was observed with tibia lead levels, whereas no association was observed with blood lead levels. In cross-sec- tional analyses of the same population, higher blood lead levels were a stronger predictor of poorer performance on the MMSE, as were higher patella and tibia bone lead levels (Payton et al. 1998; Wright et al. 2003). I n a s t u d y o f a l m o s t 1 , 0 0 0 p e r s o n s 50–70 years of age randomly selected from the general population in the Baltimore Memory Study (BMS), a cross-sectional analysis showed that relatively low current blood lead levels were not associated with cognitive domain scores. However, moderate tibia lead levels (mean ~ 19 µg/g) were signiﬁ- cantly associated with worse performance in all seven cognitive domains (Shih et al. 2006). Thus, in the environmental studies of older adults, the most consistent findings across Table 2. Detailed summary and main ﬁndings of studies on cognitive function with recent and cumulative lead dose biomarkers. Sample size (no.) Author Nonoccupational lead exposure Stokes 257 (E) XS et al. 276 (R) 1998 Payton et al. 1998 Wright et al. 2003 141 736 blood, tibia, patella lead 295 blood only Weisskopf 466 et al. F/U = 61.9% 2004 Weisskopf 1,089 blood et al. 761 tibia 2007 760 patella Shih, et al. 994 2006 Occupational lead exposure Lindgren 467 et al. 1996 XS XS L XS and L XS XS Environmental Health Perspectives • VOLUME 115 | NUMBER 3 | March 2007 Percent male [mean age in Design years (SD)] Race/ ethnicity (%) Source of Pb exposure 47.7% (E) 24.3 (3.2) 49.6% (R) 24.2 (3.0) 100% 66.8 (6.8) White (E) Resided near lead 98 smelter during White (R) childhood (E) 94.2 Random sample of licensed drivers (R) White Environmental 94 (Normative Aging Study) 100% 68.2 (6.9) White 94 100% 67.4 (6.6) White 94 100% 68.7 (7.4) White 98 Environmental (Normative Aging Study) Environmental (Normative Aging Study) Environmental (Normative Aging Study) 34.1% 59.4 (6.0) African American 40.1 Environmental (Baltimore Memory Study) 100% 43.4 (11) White 100 Canadian lead smelter (Canada Lead Study) 370 currently employed 97 previously employed Primarily current/ past exposure Past (E) ~ 20 years prior Past Past Past Past Past Lead dose measure [mean (SD)] Blood: (E) 2.9 (3.3) (R) 1.6 (1.4) Tibia: (E) 4.6 (range, –28.9 to 37) (R) 0.6 (range, –46.4 to 17.4) Blood: 5.5 (3.5) Tibia: 22.5 (12.2) Patella: 31.7 (19.2) Blood: 4.5 (2.5) Tibia: 22.4 (15.3) Patella: 29.5 (21.2) Median [IQR] Blood: 4 [3, 5] Tibia: 19 [12, 26] Patella: 23 [15, 35] Median [IQR] Blood: 5 [3, 6] Tibia: 20 [13, 28] Patella: 25 [17, 37] Blood: 3.5 (2.2) Tibia: 18.7 (11.2) Blood: 36 IBLa: mean across groups, 268.6–1,227.7 TWAb: mean across groups, 26.1–52.8 Covariates adjusted for outcome measures Age, education, sex, height, BMI Battery of tests— 6 domains Summary of ﬁndings Dichotomized exposure group associated with neurobehavioral outcomes, but no signiﬁcant associations between tibia lead and neurobehavioral outcomes Age, education Blood lead signiﬁcant predictor of Battery of tests— performance on speed, memory, spatial 8 domains copying, and vocabulary Tibia lead associated with pattern memory and spatial copying Patella lead had less signiﬁcant relationships with test scores than tibia lead Age, education, alcohol Blood lead OR = 1.21 (95% CI, 1.07–1.36) intake for MMSE < 24 MMSE score < 24 Tibia lead OR = 1.02 (95% CI, 1.00–1.03) for MMSE < 24 Patella lead OR = 1.02 (95% CI, 1.00–1.04) for MMSE < 24 Patella and blood lead levels modiﬁed the effect of increasing age on MMSE score Age, smoking, education, Null association between baseline alcohol intake, and blood lead and change in MMSE years between MMSE Patella lead signiﬁcantly associated with tests decline in MMSE (an IQR higher patella Change in MMSE score lead = ~ 5 years of aging on baseline MMSE) Tibia lead similar to patella but not quite signiﬁcant Age, age squared, XS analysis: blood lead signiﬁcant education, smoking, predictor of performance on vocabulary and alcohol intake test Battery of 10 cognitive L analysis: tibia lead associated with tests pattern comparison L analysis: patella lead associated with pattern comparison and spatial copying Series of 5 models Tibia lead was consistently associated adjusting for age, sex, with lower test scores in all 7 cognitive APOE e4 allele, domains education, race, wealth Blood lead was not associated with any Scores in 7 cognitive cognitive domain domains Age, education, language, depressive scale score, head injury, neurological disorder, alcohol use Battery of tests— 8 domains Lack of association between neuropsychologic performance and blood lead or TWA IBL related to visuomotor skills, psychomotor speed and dexterity, motor speed, and verbal memory performance Continued, next page 485