Long-Term Cannabis Use and Cognitive Reserves and Hippocampal Volume in Midlife

Abstract

Objective: Cannabis use is increasing among midlife and older adults. This study tested the hypotheses that long-term cannabis use is associated with cognitive deficits and smaller hippocampal volume in midlife, which is important because midlife cognitive deficits and smaller hippocampal volume are risk factors for dementia.

Methods: Participants are members of a representative cohort of 1,037 individuals born in Dunedin, New Zealand, in 1972-1973 and followed to age 45, with 94% retention. Cannabis use and dependence were assessed at ages 18, 21, 26, 32, 38, and 45. IQ was assessed at ages 7, 9, 11, and 45. Specific neuropsychological functions and hippocampal volume were assessed at age 45.

Results: Long-term cannabis users showed IQ decline from childhood to midlife (mean=-5.5 IQ points), poorer learning and processing speed relative to their childhood IQ, and informant-reported memory and attention problems. These deficits were specific to long-term cannabis users because they were either not present or were smaller among long-term tobacco users, long-term alcohol users, midlife recreational cannabis users, and cannabis quitters. Cognitive deficits among long-term cannabis users could not be explained by persistent tobacco, alcohol, or other illicit drug use, childhood socioeconomic status, low childhood self-control, or family history of substance dependence. Long-term cannabis users showed smaller hippocampal volume, but smaller hippocampal volume did not statistically mediate cannabis-related cognitive deficits.

Conclusions: Long-term cannabis users showed cognitive deficits and smaller hippocampal volume in midlife. Research is needed to ascertain whether long-term cannabis users show elevated rates of dementia in later life.

Keywords: Cannabis; Cognition/Learning/Memory; Neuroimaging; Substance-Related and Addictive Disorders.

Figure 1A.

Long-Term Cannabis Use and Neuropsychological Functions. A comparison of long-term cannabis users with 5 informative subgroups on age-45 test performance across specific neuropsychological domains. This figure shows means (and 95% CIs) on age-45 neuropsychological tests, which were adjusted for sex and childhood IQ and standardized on the full cohort (M=0, SD=1). Average normative performance is indicated by the reference line at the representative cohort mean of 0. Estimates below zero indicate poorer than average test performance. Stars indicate mean scores that were statistically significantly better (p<.05) as compared with long-term cannabis users, after adjustment for sex and childhood IQ. Rey Total=Rey Auditory Verbal Learning Test total score (learning). Rey Recall=Rey Auditory Verbal Learning Test delayed recall (memory). WMS=Wechsler Memory Scale Months Backwards test. WMI=Working Memory Index. PRI=Perceptual Reasoning Index. VCI=Verbal Comprehension Index. PSI= Processing Speed Index.

Figure 1B.

Long-Term Cannabis Use and Hippocampal Volume. A comparison of long-term cannabis users with 5 informative subgroups on age-45 hippocampal volume. This figure shows means (and 95% CIs) on age-45 hippocampal volume, which were adjusted for sex and standardized on the full cohort (M=0, SD=1). Average normative volume is indicated by the reference line at the representative cohort mean of 0. Estimates below zero indicate smaller than average volume. Stars indicate mean volumes that were statistically significantly larger (p<.05) as compared with long-term cannabis users, after adjustment for sex. CA1-CA4=cornu ammonis 1–4. HATA=hippocampal amygdala transition area.