The Precursors Study provided an unprecedented opportunity for reexamining the Nun Study findings among respondents with markedly different gender, education, and occupation profiles. Our results indicate that propositional density in early-life writing is associated with a later-life AD diagnosis in a sample of mostly male medical-school graduates. Low propositional density scores might identify those at greater risk of developing AD, whereas the ability to produce idea-packed sentences in young adulthood could be an early signal of cognitive reserve, an active buffer against the effects of neuropathology. Though the observed difference in propositional density between cases and controls was considerably smaller in the Precursors Study than it was among participants in the Nun Study, it was statistically significant in a simple test of mean differences and in a more robust regression analysis.
Whereas the Nun Study consisted exclusively of women, more than 72% of the Precursors Study participants were male. It has long been known that females tend to perform better than males at tasks involving verbal fluency, perceptual speed, and verbal and item memory (Kimura, 1996
). Sex differences in size (adjusted for overall brain volumes) have been reported for numerous cortical regions, including those influencing language, such as the superior temporal gyrus and Broca's area (Goldstein et al., 2001
; Harasty, Double, Halliday, Kril, & McRitchie, 1997
; Schlaefer et al., 1995
). Recent studies have not, however, established any consistent or statistically significant neurobiological basis for sex differences in language function (Ihnen et al., 2009
; Sommer, Aleman, Somers, Boks, & Kahn, 2008
). Although sex differences have not been linked to odds of diagnosed AD, the same level of AD pathology (neuritic plaques and neurofibrillary tangles) is more likely to be clinically diagnosed as AD in women than in men (Barnes et al., 2005
). Our matched design controlled for potential sex differences in the pooled analysis, and propositional density differences between cases and controls were apparent in this predominantly male sample.
The Precursors sample differs from the nun sample on common proxy measures of cognitive reserve including education, occupational attainment, and socioeconomic status. Whereas most of the nuns completed a high-school diploma before entering the convent, the Precursors Study participants completed undergraduate education prior to entering medical school. The majority of nuns subsequently earned a bachelor's degree, whereas the Precursors Study members earned a medical degree. The nuns were professionally engaged in teaching, and the Hopkins graduates had careers in medicine or related fields. As members of a religious community, the nuns took vows of chastity, poverty, and obedience and shared a common lifestyle. The opportunities open to graduates of a prestigious medical school likely led the Precursors Study participants to lifestyles quite distinct from those of the nuns.
Though higher income and increased educational and occupational attainment are jointly and independently protective against dementia (Richards & Sacker, 2003
; Stern et al., 1994
), propositional density scores in the Precursors Study were lower than those for the nuns. This finding might reflect varied writing styles across the two populations (potentially associated with differences in sex composition, occupation, or other characteristics), differences in their essay prompts, or distinctions in the motivation with which the two groups approached their writing.
Notably, the nuns’ propositional density was assessed by humans, whereas our results are based on computer-generated scores. However, Brown et al. (2008)
reported high correlation (r
= .97) between CPIDR's scores and those by humans, and results for our sample using hand-coded scores (not shown) did not differ substantially from those reported above.
A few potential limitations have to do with the selection of cases and controls. First, selecting cases nested in a cohort makes it difficult to distinguish between the exposure/disease and exposure/survival associations. Because Snowdon, Greiner, Kemper, Nanayakkara, and Mortimer, (1999)
showed higher all-cause mortality for those with low propositional density, it is possible that individuals with lower propositional density died before developing AD. However, the relative youth of the sample may mitigate this potential selection bias. Furthermore, cases were identified based on assessment of study data by a team of medical experts following ICD-9 guidelines, not via a definitive postmortem neuropathological diagnosis. Due to this classification system, our study may have excluded AD cases from the sample, but was unlikely to include cases with non-AD forms of dementia. Notably, this type of potential classification error would bias our analysis against a significant result, rendering the significant association we report above conservative.
Finally, due to the cumulative incidence sampling procedure, all study participants who were not diagnosed with cognitive impairment at the time of sampling (2007) were eligible for inclusion as controls. It remains possible that current controls may become cases in the future and that the propositional density association we found applies particularly to early-onset AD. This potential misclassification would also bias the results toward the null hypothesis of no difference between the groups and again render our findings conservative. Further analysis as the study cohort ages may allow more definitive conclusions about the longitudinal relationship of linguistic complexity with cognitive pathology.
An association between cognitive ability measured in early life and information-processing speed at older ages was reported by Luciano and colleagues (2009)
, though the correlation was lower in carriers of the APOE-e4 allele. Distinct from markers of biological vulnerability to AD such as APOE-4, propositional density potentially reflects cognitive reserve, a factor that influences the brain's capacity for compensation through life span pathways that remain to be elucidated. Due to the selected nature of the Precursors sample, further studies involving participants with more varied educational, socioeconomic, and racial/ethnic backgrounds are needed. Although it remains unclear whether writing idea-dense prose is a protective activity or an indicator of underlying cognitive reserve, it is a compelling marker of AD risk that could be beneficially incorporated into future studies of cognitive change across the life course.