Date Published: July 18, 2018
Publisher: Public Library of Science
Author(s): Miriam A. Mosing, Cecilia Lundholm, Sven Cnattingius, Margaret Gatz, Nancy L. Pedersen, Carol Brayne
Abstract: BackgroundThere is evidence for long-lasting effects of birth characteristics on cognitive ability in childhood and adulthood. Further, low cognitive ability throughout the lifetime has been linked to age-related cognitive decline and dementia risk. However, little is known about the effects of birth characteristics on cognitive dysfunction late in life. Here we explore potential associations between birth characteristics (weight, head circumference, length, and gestational age), adjusted and not adjusted for gestational age, and cognitive impairment and dementia late in life.Methods and findingsData from twins in the Swedish Twin Registry born 1926–1960 were merged with information from the Swedish birth, patient, and cause of death registries, resulting in a sample of 35,191 individuals. A subsample of 4,000 twins aged 65 years and older also participated in a telephone cognitive screening in 1998–2002. Associations of birth characteristics with registry-based dementia diagnoses and on telephone-assessed cognitive impairment were investigated in the full sample and subsample, respectively. The full sample contained 907 (2.6%) individuals with a dementia diagnosis (an incidence rate of 5.9% per 100,000 person-years), 803 (2.4%) individuals born small for gestational age, and 929 (2.8%) individuals born with a small head for gestational age. The subsample contained 569 (14.2%) individuals with cognitive impairment. Low birth weight for gestational age and being born with a small head for gestational age were significant risk factors for cognitive dysfunction late in life, with an up to 2-fold risk increase (p < 0.001) compared to infants with normal growth and head size, even after controlling for familial factors, childhood socioeconomic status, and education in adulthood. In line with this, each additional 100 g birth weight and each additional millimeter head circumference significantly reduced the risk for dementia (hazard ratio 0.98, 95% confidence interval 0.97 to 0.99, p = 0.004) and cognitive impairment (odds ratio 0.99, 95% confidence interval 0.99 to 1.00, p = 0.004), respectively. Within-pair analyses of identical twins, though hampered by small sample size, suggested that the observed associations between birth characteristics and dementia are likely not due to underlying shared genetic or environmental etiology. A limitation of the present study is that registry-based dementia diagnoses likely miss some of the true dementia cases in the population. Further, a more precise measure of cognitive reserve early in life as well as a date of onset for the cognitive impairment measure in the subsample would have been favorable.ConclusionsIn this study, we found that infants of smaller birth size (i.e., low birth weight or small head circumference adjusted and unadjusted for gestational age) have a significantly higher risk of age-related cognitive dysfunction compared to those with normal growth, highlighting the importance of closely monitoring the cognitive development of such infants and evaluating the potential of early life interventions targeted at enhancing cognitive reserve.
Partial Text: Associations between cognitive function and anthropometric measures in childhood and adulthood, such as body height and head circumference, are well documented. Several studies have reported positive associations of cognitive ability with body length in childhood  and in adulthood [2,3], as well as with childhood and adult head circumference [2,4–6]. Further, both adult height and head circumference have been shown to be negatively associated with late life cognitive decline [6–8] and dementia [9–12].
The present study explored associations between birth characteristics (BW, BL, HC, and GA) and dementia and cognitive impairment later in life. Overall, lower BW and smaller HC showed associations in the expected direction, resulting in increased risks for age-related cognitive dysfunction, i.e., dementia or cognitive impairment. For dementia, lower BW (independent of GA) was a significant risk factor, with a 2% higher risk with each 100 g lower BW and about 22% higher risk if weighing less than 2.5 kg at birth. Similar associations were observed when BW was adjusted for GA, with a 9% risk reduction for dementia for each additional standard deviation BWGA and a 17% risk increase for individuals born SGA, though the latter was not significant. HC was a significant risk factor only when the head was SGA (65% risk increase), suggesting harmful effects of reduced fetal growth for dementia. Similarly, detrimental effects were observed for cognitive impairment, with individuals born SGA and with SHCGA showing approximately 73% and 124% higher odds, respectively. In addition, larger HC was, independent of GA as well as adjusted for GA, a significant protective factor for cognitive impairment (but not for dementia), with each additional millimeter resulting in a 1% lower odds for cognitive impairment and each additional SD HCGA resulting in a 15% lower odds. BL and GA (independent of other birth characteristics) showed no significant association with late life cognitive dysfunction. Overall, these findings suggest negative long-term effects of small birth size on risk of cognitive dysfunction late in life, with additional protective effects of each extra 100 g of BW for dementia and each additional millimeter of HC for cognitive impairment (independent of GA).