Table 1.
Epidemiology literature summary for lead exposure and Alzheimer’s disease or cognitive decline
| Reference | Study Design | Population | Exposure | Outcome | Main Findings |
|---|---|---|---|---|---|
| Alzheimer’s Disease | |||||
| Graves, 1991 [224] | Meta-analysis | Four case-control studies of AD in 4 US cities (Bedford, Durham, Denver, Minneapolis); 221 cases and 287 controls | Exposure to Pb at work | AD (unspecified) | RR = 0.71 (95% CI: 0.36–1.41) |
| Emard, 1994 [63] | Retrospective ecological | 129 definite or probable AD cases born in the Saguenay-Lac-Saint-Jean territory of Quebec | Difference between birthplace residential and municipal average levels of Pb in soil | AD clinical diagnosis | Number of cases with higher average Pb concentration near residence at birth in comparison to municipal average (n = 49) differs from number of cases with lower average Pb concentrations near residence at birth in comparison to municipal average (n = 15) P <0.05 |
| Gun, 1997 [56] | Case-control | 170 newly referred cases of probable or possible AD from 2 hospitals in Sydney, Australia; 170 age- and sex-matched individuals recruited from general practice | Exposure status based on interview and occupational exposure information (never, possible, probable) | AD clinical diagnosis | OR=1.12 (95% CI: 0.63–2.00) of AD for possible/probable versus never exposure |
| Cognitive function | |||||
| Stokes, 1998 [225] | Retrospective cohort | 257 young adults ages 19–29 who lived 5 towns surrounding lead smelter in Silver Valley, ID (exposed) versus 276 licensed drivers ages 19–29 living in Spokane, WA (referent) | Living in one of 5 towns surrounding lead smelter while 9 months to 9 years of age from 1974–1975 | CNS outcomes including cognitive, mood, and Swedish Q16 | The exposed (versus the referent) was associated with 0.169 seconds longer on concept shifting task; 0.117 more errors on symbol digit substitution; 0.155 more errors on learning/attention task (serial digit learning); 0.115 more errors on non-verbal intelligence task, and 0.167 |
| Payton, 1998 [57] | Cross-sectional | A subset of 141 men from the NAS (mean age 66.8, SD: 6.8) | Blood Pb (μg/dl), patella Pb and tibia Pb (ĝ Pb/g bone mineral) | Neuropsych battery including portions of NES2, WAIS-R and CERAD | fewer correct on vocabulary test Blood Pb (1 μg/dl increase) was associated with 0.84 (SE: 0.2) fewer points on the vocabulary test, 0.18 (SE: 0.09) fewer words recalled on word memory test, and 0.1 (SE: 0.04/) fewer points on the spatial copying test. Tibia Pb (1 μg Pb/g bone increase) is associated with 0.031 (SE: 0.012) fewer points on the spatial copying test. |
| Wright, 2003 [58] | Cross-sectional | A subset of 736 men from NAS (mean age 68.2, SD: 6.9) | Blood Pb (μg/dl), patella Pb and tibia Pb (μg Pb/g bone mineral) | MMSE score | OR = 2.1 (95% CI 1.1–4.1) of MMSE<24 for highest versus lowest quartile of patella Pb OR = 3.4 (95% CI 1.6–6.2) of MMSE<24 for highest versus lowest quartile of blood Pb |
| Weisskopf, 2004 [61] | Prospective | A subset of 466 men from NAS (mean age 67.6, SD 6.6) | Blood Pb (μg/dl), patella Pb and tibia Pb (μg Pb/g bone mineral) | MMSE score on two separate occasions, average 3.5 years (SD 1.1) apart | 1 IQR (20 μg/g of bone mineral) higher patella Pb was associated with −0.24 (95% CI: −0.44, −0.05) points on MMSE. 1 IQR (14 μg/g bone mineral) higher tibia Pb was associated with −0.17 (95% CI: −0.38, 0.04) points on MMSE. |
| Shih, 2006 [59] | Cross-sectional | Subset of 985 participants of the Baltimore Memory Study (mean age 59.39, SD: 5.96), a longitudinal cohort study of adults randomly selected from 65 neighborhoods in Baltimore, MD. | Blood Pb (μg/dL), tibia Pb (μg/g bone) | Scores for testing in 7 cognitive domains (language, processing speed, hand-eye coordination, executive functioning, verbal memory and learning, visual memory, and visuoconstruction | Tibia Pb associated with −0.0046 (SE: 0.002) change in language domain average z-score, −0.0053 (SE: 0.018) change in executive functioning domain average z-score,−0.0054 (SE: 0.0023) change in visual memory and learning domain average z-score, −0.0046 (SE: 0.0023) change in visual memory domain average z-score, −0.0091 (SE: 0.0025) change in visuoconstruction domain average z-score. |
| Farooqui, 2017 [62] | Longitudinal | A subset of men from the NAS, 741 with MMSE scores (mean age 67.77, SD: 6.82), 715 with global cognition measures (mean age 68.43, SD: 7.11) | Patella and tibia Pb (μg/g bone) | MMSE; Global cognition score (average Z-score from 6 tests from NES2, CERAD, and WAIS-R) | 21 μg/g higher patella Pb (1 IQR) associated with −0.13 lower baseline MMSE (95% CI: −0.25, −0.004) and faster longitudinal MMSE decline (−0.016 units/year, 95% CI: −0.032, −0.0004), and increased risk of MMSE score below 25 (HR = 1.21, 95% CI: 0.99, 1.49). |
AD, Alzheimer’s disease; RR, relative risk; OR, odds ratio; SD, standard deviation; NAS, VA Normative Aging Study; NES2, Neurobehavioral Evaluation System 2; WAIS-R, Weschler Adult Intelligence Scale; CERAD, Consortium to Establish a Registry for Alzheimer’s Disease; ALS, amyotrophic lateral sclerosis; SE, standard error; CI, confidence interval; K-XRF, K-Shell X-ray fluorescence; MMSE, Mini-Mental State Examination; PNS, peripheral nervous system; CNS, central nervous system; HR, hazard ratio