Shih et al. bone lead stores; b) the error in measurement of tibia lead levels is larger than that for blood lead; c) controlling for cross-sectional associa- tions could obscure longitudinal ones; and d) lead in blood reﬂects recent external expo- sure, and is in equilibrium with bone lead stores, possibly taking away explained vari- ance from bone lead associations via this cor- relation in cross-sectional analyses. Results of a cross-sectional analysis of former organolead workers showed that higher peak tibia lead levels (range, –2.2 to 105.9 µg/g) were related to poorer functioning on a number of cognitive tests, including those assessing manual dexterity, executive ability, verbal intelligence, and verbal memory (Stewart et al. 1999). In a longitudinal analysis Table 2. Continued. Sample size 254 Design XS 576 with all visits F/U: all 3 visits, 2 visits, 1 visit = 72%, 16%, 12% Author Bleecker et al. 2005 Schwartz et al. 2005 Winker 48 (E) et al. 2005 48 (NE) Dorsey et al. 2006 652 % Male mean age (SD) 100 41 (9.4) 76 41.4 (9.5) at visit 1 Race/ ethnicity (%) White 100 Asian 100 100 39.6 (8.8) (E) 39.9 (8.8) (NE) NR 77 43.4 (9.6) Asian 100 L XS XS XS in this same population, among 535 lead workers exposed a mean of 16 years before, increases in peak tibia lead levels [mean ± SD = 22.6 ± 16.5 µg/g] but not in blood lead levels predicted declines over time in these same domains in addition to visual memory (Schwartz et al. 2000). This ﬁnding indicates that even many years after high lead exposure, and in the absence of high current lead exposure, cumulative lead dose may exert progressive effects on cognitive functioning (Links et al. 2001). Lead exposure and psychiatric symptoms. Several lines of evidence suggest that increased blood lead levels are associated with psychiatric symptoms in adults, such as depression, anxiety, irritability, and anger. For example, a cross-sectional analysis of 107 occupationally exposed individuals showed increased rates of depression, confu- sion, anger, fatigue, and tension as measured by the Profile of Mood States (POMS; McNair et al. 1971) among those with blood levels > 40 µg/dL (Baker et al. 1983). Maizlish et al. (1995) found that current and cumulative measures of blood lead levels in currently exposed lead workers were associ- ated with tension, anxiety, hostility, and depression measured by the POMS question- naire. Lindgren et al. (1996) examined the POMS’ factor structure in retired lead smelter workers and showed that the resulting “gen- eral distress” factor was signiﬁcantly related to IBL but not to current blood lead level. Source of Pb exposure Canadian lead smelter (Canada Lead Study) Primarily current/ past exposure Past Lead dose measure mean (SD) Blood: 27.7 (8.8) IBLa: 728.2 (434.4) TWAb: 39.0 (12.3) Storage-battery plant (E) Steel production plant (NE) (Austria Lead Study) Battery, lead oxide Current Blood: 31.4 (14.2) or car radiator Mean job Tibia: 38.4 (43) manufacturing duration: and secondary 8.5 (6.3) lead smelters (71, 97, 150 (Korea Lead no longer Study) working in lead industry at visits 1,2,3) Past Blood lead: Mean of 5.2 5.4 (2.7) (E) years since 4.7 (2.5) (NE) last exposure IBLh: 4,153.3 (3,690.3) (E) Battery, lead oxide Current or car radiator Mean job manufacturing duration: and secondary 10 (6.5) lead smelters (Korea Lead Study) Storage-battery plant (E) Storage-battery plant, police ofﬁcers (Formerly E) (Austria Lead Study) Current 11.7 (9.0) mean years of exposure duration Past 5.26 (3.5) mean years since last exposure Blood: 30.9 (16.7) Tibia: 33.5 (43.4) Patella: 75.1 (101.1) Blood lead: 30.8 (11.2) (E) 5.4 (2.7) (Formerly E) IBLh: 4,613.5 (4,187.6) (E) 4,153.3 (3,690.3) (Formerly E) Covariates adjusted for outcome measures Summary of ﬁndings Age, educational Signiﬁcant amount of variance in achievement recognition and delayed recall accounted Verbal learning and for only by measures of IBL and TWA memory The “generalized memory impairment group” had the highest TWA and IBL compared with the “no impairment” and “retrieval difﬁculties” groups Age, education, sex, Blood lead cross-sectionally was height, BMI associated with lower executive ability Battery of tests— and manual dexterity scores 9 domains Change in blood lead was associated with longitudinal declines in few tests Tibia lead was associated with longitudinal declines in manual dexterity, executive abilities, neuropsychiatric and peripheral sensory function Age, years of education, Blood lead was correlated with verbal intelligence, visuospatial abilities, attention, visual number of alcoholic scanning, and visuomotor speed. IBL was drinks per week/grams correlated only with choice reaction of alcohol per week No differences between groups on Battery of tests— neurobehavioral tests, and no 5 domains differences between groups stratiﬁed by high IBL (> 4,500) vs. low IBL (< 4,500) Series of four models Ranked blood lead was associated with adjusting for age, sex, executive ability, manual dexterity, and education, job duration, PNS sensory function height, BMI Ranked tibia lead was similar to blood Battery of tests— lead but also associated with 14 neurobehavioral, psychomotor speed 4 peripheral nervous Ranked patella lead was associated with system measures, and executive ability, manual dexterity, psychiatric symptoms depressive symptoms, and PNS sensory function. Adjustment for blood lead attenuated these associations Age Visuospatial abilities and executive Battery of tests— functioning performance decreased 5 domains linearly from workers with short exposure duration and long absence from exposure, to the worst performing group with long exposure and short/no absence from exposure Winker et al. 2006 47 (E) 48 (formerly E) 100 39.5 (9.7) (E) 39.6 (8.8) (Formerly E) NR Abbreviations: APOE, apolipoprotein E; BMI, body mass index; CI, conﬁdence interval; E, exposed; F/U, follow-up rate; IQR, Interquartile range; L, longitudinal; MMSE, Mini-Mental State Examination; NB, neurobehavioral; NE, nonexposed; Pb, lead; PNS, peripheral nervous system; OR, odds ratio; R, reference; XS, cross-sectional. Blood lead units: µg/dL; tibia/patella lead units: µg/g (unless noted otherwise). IBL: integrated blood lead calculated from blood measures during a time period, a measure of cumulative dose: aµg-years/dL; gµmol-years/l; hµg-months/dL. TWA: time weighted average calculated by dividing IBL by number of years exposed, a measure of average intensity of lead exposure: bµg/dL; fµmol/L. cCumPb: Area under the curve of blood lead levels over time: µg-years/dL. dCurrent and peak blood lead measured in units µmol/L. eCBLI: cumulative blood lead index: product of blood lead and employment time: µmol-months/L. 488 VOLUME 115 | NUMBER 3 | March 2007 • Environmental Health Perspectives