Running head: Examining effects of adolescent substance use on cognitive performance across the lifespan

Examining the Effects of Adolescent Substance Use on Cognitive Performance Across the

Lifespan

Jillian Battista
Examining the effects of adolescent substance use on cognitive performance across the lifespan

Introduction

Aging and substance use research have many interconnected areas of focus, such as

cognitive function, drug-medication interactions, and psychiatric comorbidities (Kalapatapu et

al., 2017). Independently, these domains can induce biological, psychological, and cognitive

changes within the body and brain (Peters, 2006; Gould, 2010). Though the research on the

interplay of these domains is limited, the aging population and individuals with addiction are

complexly related and have increasing similarities. As one example, individuals with past and

current substance misuse, as well as aging individuals, have shown cognitive deficits,

specifically in inhibition and attention. More specifically, aging adults and people with substance

use history have shown deficits in working memory, selective attention, cognitive flexibility, and

inhibitory control (Valeriani et al., 2003; Harada et al., 2013; Koob & Volkow, 2016).

Additionally, studies investigating these populations separately reported commonality,

specifically in reductions in brain matter, structure, and function (Peters, 2006; Koob & Volkow,

2016). Due to these growing similarities, there is evidence of accelerated biological and

cognitive aging due to drug addiction through inflammation, oxidative stress, and comorbidities

(Bachi et al., 2017).

Despite the apparent crossover between substance use and aging within multiple areas of

cognition and biology, it remains unknown how influences of lifestyle, such as heavy use of

substances during the lifespan, could potentially impact normal cognition and executive function

throughout the aging process. Moreover, the specific effects of substance use within the lifespan

on normal cognitive aging could lead to heightened and accelerated cognitive deficits in older

adults with a history of substance use, and therefore, increase the likelihood of developing

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Examining the effects of adolescent substance use on cognitive performance across the lifespan

cognition-related disorders, such as mild cognitive impairment (MCI) and Alzheimer’s disease

(AD).

Typically, investigations of substance use in aging populations comprise of individuals

with a current use of substances or past use of substances within another area of the lifespan.

Presently, the long-term effects of prior substance use from a developmental standpoint have

been under investigation (Kuerbis et al. 2014; Kelly et al., 2015; Morin et al., 2019). Starting in

childhood, genetic and environmental influences, such as parental substance use, trauma, and

peer pressure, have been shown to influence substance use initiation and propagation from

adolescence well into adulthood (Gould, 2010). Many studies investigating the effect of

substance use tend to examine cognitive function at one time point, so the present study aims to

improve that limitation with a thorough examination across the lifespan.

Adolescent substance use, as well as subsequent drug addiction and substance use

disorders (SUDs), has been shown to have significant and long-lasting deficits in brain function

and behavior (Odgers et al., 2008; Gould, 2010). Individuals who use substances within

adolescence are more likely to have increased in risk-taking, impaired decision making, reduced

hippocampal volume, and reduced white matter maturation (Squeglia et al., 2009). Similarly, the

aging process is a lifelong development that alters the brain and body (Harada et al., 2013).

Particularly, however, use of substances within adolescence can negatively impact cognition,

physical health, and even mental health, due the vast amount of physical and emotional

alterations within this period. Moreover, animal models show these effects may be specific to the

type of substance (Mooney-Leber & Gould, 2018). Substance use not only has acute effects

within adolescence, but there is evidence of long-term and chronic alterations, as well as

substantial likelihood of development into SUDs (Chassin et al., 2009). Based on previous

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Examining the effects of adolescent substance use on cognitive performance across the lifespan

literature, this points to a potential role of drug addiction, stemming from adolescence, in the

acceleration of cognitive function during the aging process, and leading to increased deficits in

older adulthood. However, a specific examination of adolescent substance use on cognitive

abilities in an aging population is deficient within the current literature.

It is important to highlight that there is growing evidence that substance use throughout

the lifespan negatively correlates with life expectancy and can hinder investigation within a

lifespan approach. Individuals who use substances are more likely to enter risky and life-

threatening situations, and additionally, they have higher rates of automobile accidents,

attempted suicide, and overdoses (Glei & Preston, 2020). All of these circumstances may inhibit

the longitudinal investigations, simply due to premature death within individuals who use

substances.

However, using modern techniques and tasks, the present study aimed to investigate a

sample of individuals, who either have a history of substance use or no reported history of

substance use within adolescence, over the course of their lifetime in an attempt to dissect the

cognitive deficits associated with substance use and normal cognitive aging. A schematic of the

proposed experimental investigations can be found in Figure 1.

Figure 1. Schematic representation of the present study investigations (yellow arrow).

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Examining the effects of adolescent substance use on cognitive performance across the lifespan

A longitudinal design was necessary to observe lifelong changes on cognition and to

draw conclusions on varying deficits (or constancy) on brain function due to adolescent

substance use. Cognitive tasks, including the Stroop task, Go/No-go task, Wisconsin Card

Sorting Task, and Digit Span task, were executed during an initial baseline visit and the

subsequent 7 follow-up visits every 10 years. These tasks were selected to examine selective

attention, inhibitory control, cognitive flexibility, and working memory, respectively, within a

population starting in adolescence.

Through examination of a history of substance use from adolescence in comparison to a

healthy group over the lifespan, it is hypothesized that a history of substance use will have a

long-lasting effect on cognitive brain function and behavior. Within this long-lasting deficit, it is

estimated that, within this sample, substance use in adolescence would have accelerated normal

cognitive aging and resulted in deficient executive function, as well as increased risk for

cognitive deficit disorders, such as MCI and AD. Furthermore, due to the severe influences on

cognitive function from aging and addiction, it is also hypothesized that those with a history of

substance use in adolescence will have the strongest deficits in selective attention and inhibitory

control, thereby illustrated by a reduction in performance accuracy on the respective tasks over

the study course.

With further investigation into this unexplored area, there is potential to discover how

substance use in a highly significant developmental period, in addition to normal cognitive

aging, could have long-lasting effects on cognition and brain function. Moreover, a new target

population for therapeutic intervention may be applicable and is discussed further.

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Examining the effects of adolescent substance use on cognitive performance across the lifespan

Methods

Participants and Study Design

Participants within this study consisted of 1,000 individuals initially recruited between

the ages of 10 and 19 and followed through their lifetime until they were between the ages of 70

and 80. Participants were recruited from the surrounding elementary and middle school

community via flyers and emails. Initial inclusion/exclusion criteria were limited, but generally,

individuals had to be within the ages of 10 and 19, have no present diagnoses (or history) of

cancer or other life-threatening illnesses, and have parental consent before the age of 18. Once

the individual was 18, parental consent was no longer required for participation. Additionally,

individuals with preexisting cognitive or attention deficit disorders (determined prior or after

baseline visit) were excluded from the study. Participants were compensated for their

participation.

Each participant had an initial visit for data collection followed by a visit every 10 years

to examine changes across the lifespan. Between visits, participants were provided with

supportive encouragement through yearly holiday cards and phone calls to maintain involvement

and prevent attrition. Participants were also asked to provide the research team with updated

contact information to prevent loss of communication.

Data Collection

Each visit consisted of demographic data collection, a Structured Clinical Interview for

the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5; SCID), and a

battery of cognitive tasks across various domains. At each visit, basic demographics, such as age,

race, ethnicity, socioeconomic status, employment status and education, were collected, along

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Examining the effects of adolescent substance use on cognitive performance across the lifespan

with trauma history, psychological disorder history, and substance use history. The details of

substance use history were accurately documented at each visit, including estimated age use

started, approximately how long it lasted, what the drug of choice was, and the estimated amount

of usage. For substances, the Timeline Follow-back (TLFB; Sobell & Sobell, 1992) scales were

used to quantify usage. The TLFB quantifies standardized substance usage via recall and

retrospective analysis over a designated period of time, allowing for standard examination of

substances across the lifespan.

Following the second visit, when the participant was between the ages of 20 and 29, and

an additional collection of substance use history, participants were divided into 2 groups—an

“non-exposed” group (individuals with no prior substance use history within adolescence), and

an “exposed” group (individuals with a history of past substance use within adolescence).

Cognitive Tasks

A battery of computerized cognitive tasks was administered during each visit to

investigate cognitive domains that are most heavily influenced by aging and substance use. The

four executive functions that were selected were selective attention (Stroop Test), inhibitory

control (Go/No-go Test), cognitive flexibility (Wisconsin Card Sorting Task), and working

memory (Digit Span Test) at a performance level. Selective attention requires the individual to

put their attention toward one stimulus and inhibit all other stimuli. Similarly, inhibitory control

tests for the participant’s ability to inhibit impulses, habits, and routines. Cognitive flexibility

measures the ability of the subject to change the cognitive ‘rules’ and adhere to new rules.

Lastly, working memory examines short-term memory formation through immediate and

conscious processing. Images of task setup and design can be found in Figure 2.

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The Stroop Task (Figure 2a) is a well-tested and widely used psychological measurement

of attention and inhibition using colors and words, wherein a word of a color (i.e. “Yellow”) is

presented, however, the word is written in another color (i.e. in red font) (Stroop, 1935). The

participant is asked to respond noting what the color of the word is and ignore the actual word,

which requires selectively attending to one feature and ignoring all others. Results were

measured via reaction time (RT), as well as perseverative errors and false alarms.

The Go/No-go Task (Figure 2b) requires execution of a quick motor response in the

presence of specific stimuli (“go” stimuli) and inhibition of that response in the presence of other

stimuli (“no-go” stimuli). For example, when an “X” appears on the screen followed by a “Y”,

participants ‘go’ (or become active in their response), however, when an “X” appears followed

by another “X”, participants ‘no-go’ (or inhibit their motor response). This task tested the ability

to control inhibition and act only when appropriate stimuli was presented. Results were measured

via reaction time (RT) and percent of errors.

To test cognitive flexibility, the Wisconsin Card Sorting Task (WCST; Figure 2c) was

executed and involves four base cards with varying colors, shapes, and quantity of shapes.

Participants were asked to place each trial card to a matching base card by guessing if the cards

matched by color, shape, or quantity. Throughout the trials, the “correct” match changed every

10 correct placements. Participants were told if they were “correct” or “incorrect”, but not which

rule was correct, allowing for acclimation to the rule followed by requirement to switch to

another rule. Results were measured by number of categories completed.

The Digit Span test (Figure 2d) is a basic neuropsychological test to measure short-term

working memory formation. A span of digits is presented to the participant and they are asked to

verbally repeat the span. As the test goes on, the number of digits in the span increases,

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becoming more difficult for the participant to form correct short-term memory of the digits.

Results were measured by the number of correct digit span recollections before three consecutive

incorrect spans.

Figure 2. Task designs for (a) Stroop Task, (b) Go/No-go Task, (c) Wisconsin Card Sorting Task, and (d) Digit Span Test.

Between-Group Task Performance Analysis

To analyze the effect of substance use in adolescence on cognition, respective task results

were analyzed separately. Two-way analysis of variances (ANOVA) analyses were executed to

determine if substance use in adolescence (independent variable) was associated with task

performance (dependent variable) at various ages in the lifespan. Sex, race, education, and

socioeconomic status variables were controlled for due to their potential influence on cognitive

performance.

Additionally, it was important to understand the area under the curve (AUC) between the

groups, highlighted by a green bracket in Figure 3. Taking the results from the non-exposed

group minus the results from the exposed group will allow us to see the exact difference in

effects of substance use without influence of normal aging.

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Expected Results/Implications

Using cognitive behavioral techniques and a lifespan approach, the present study aimed

to examine the differences within two groups of aging individuals with divergent histories of

substance use within adolescent development in hopes of drawing conclusions and inferences on

how substances may impact long-term cognition. Based on previous research and the execution

of a longitudinal study design, it is expected that the “exposed” group (with a history of

substance use in adolescence) would have long-lasting cognitive deficits, but more specifically,

in performance in selective attention and inhibitory control.

Schematic representations of expected results can be found in Figure 3. In general,

immediate effects of substance use (such as baseline tests in adolescence, as well as young

adulthood) were not expected to be drastically or significantly different between groups. Though

there are acute effects of adolescent substance use, it would be unlikely to see drastic differences

between the groups in the early stages. A slight decline in cognitive function across the lifespan

is expected, however, the strongest drop-off is expected in older adulthood, when additional

cognitive decline occurs simply due to an inevitable aging process. The start of the drop-off for

the exposed group, represented by the red circles, could occur as early as middle adulthood (as

represented in Figure 3), which is expected to be due to an accelerated cognitive aging process.

As seen in Figure 3, task scores of individuals in the exposed group at the middle adulthood

timepoint match task scores of individuals in the non-exposed group at the older adulthood

timepoint, indicating the beginning of an early cognitive performance decline from adolescent

substance use. This is representative of evidence pointing towards a long-term effect on

cognition from adolescent substance use.

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Figure 3. Expected results of adolescent substance use on task performance across the lifespan.

Figure 3 is illustrative of a general decline in cognitive function across the lifespan,

however, stronger deficits in selective attention and inhibitory control would also be expected.

Attention and inhibition are necessary and mutually inclusive cognitive functions that have

previously been shown to decline in older adults, particularly through the establishment of the

Inhibitory Deficit Theory/Hypothesis. Originally introduced by Hasher and Zacks in 1988, the

inhibitory deficit theory states that older adults have insufficient suppression and inhibition of

irrelevant information compared to young adults (Ortega et al., 2012). In turn, older adults have

inadequate abilities to attend to necessary information.

Similarly, those with a history of substance use and, therefore, an increased chance of

developing addiction, also show deficits in attention and inhibition. More specifically, changes

within the brains of individuals with addiction, such as increases in dopamine neurotransmission,

increase reactivity to drug-related stimuli which commands attention and increases the likelihood

of relapse (Koob & Volkow, 2010). Therefore, inability to inhibit salient stimuli and
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dysregulated attention potentiate the cycle of addiction, which is very similar to the inhibitory

deficit theory existent in older adults. In summation, the inhibitory deficit hypothesis, as well as

the cycle of addiction, severely impact cognitive function and, together, it is expected that they

would result in exacerbated cognitive function.

With these results, it is evident that it is necessary to examine adolescent substance use in

a developmental context. Not only does adolescence acutely effect the brain and behavior, but

there is also potential for chronic alterations in quality of life through deficits in executive

function that are heightened by harmful use of substances within this vulnerable developmental

period. Individuals who use substances would then be more likely to require home hospice care,

due to a potential inability to care for themselves, as well as additional healthcare resources, such

as health insurance. In addition, these expected results implicate a necessity for a public health

approach to adolescent substance use and require an aim to prevent and mitigate long-term

deficits throughout the lifespan. This allows the development of a new therapeutic target

population in which an adult population with a history of substance use can potentially restore

lost or declining cognitive function in an attempt to improve quality of life, as well as reduce the

likelihood of developing mild cognitive impairment (MCI) and Alzheimer’s disease (AD).

It is important to highlight the possibility that the expected results were not correct, and

the presented hypotheses were not supported. If there is no difference between the exposed and

non-exposed groups in terms of cognitive performance, a history of substance use would have

had no effect on cognition across the lifespan or in older adulthood, indicating a potential

protective effect of aging throughout the lifespan that prevents or alleviates cognitive deficits.

Additionally, after substance use, there could be a potential overcompensation of resources

within aging to reduce those deficits. This would require further investigation.

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There are various limitations to the current study. Firstly, due to the broad examination of

substance use within adolescence, the use of a variety of substances (or multiple substances)

could potentially elicit various cognitive deficits. As one example, it has been shown that

cannabis use, but not alcohol use, showed delayed effects on inhibitory control and perceptual

reasoning (Morin et al., 2019). Secondly, use of substances within adolescence has been shown

to increase the likelihood of substance use within other areas of the lifespan. Therefore, it is

unlikely that the exposed group sample would only have substance use within the adolescent

period. In fact, continued substance use beyond adolescence would likely increase possibility of

impaired cognitive function, as well as increase possibility of addiction. Subsequently, more

biological damage from substances could lead to an accelerated aging process. Lastly, it has been

shown that deficits in cognitive function increase likelihood of adolescent substance use,

indicating a potential bidirectional relationship between cognition and substance use.

Specifically, deficits in working memory were discovered to be a risk factor for as well as a

result of adolescent substance use (Khurana et al., 2017). This would require an additional

baseline examination in order to determine individual alterations in cognitive function before and

after substance use. Additionally, it may be appropriate to control for this preexisting deficit at

baseline.

Some potential future directions include adding additional tests and tasks for a better

view of cognition. Research has shown a potential for task-specific differences in cognitive

deficits, so adding more tasks would be necessary for a comprehensive examination.

Additionally, adding neuroimaging techniques would allow for a better look at brain function

and structure across the lifespan, as well as changes in function during specific tasks. Lastly,

though mentioned briefly, genetic influences on cognition and addiction susceptibility would be

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an important next step in order to examine how heritable factors would interact with the aging

process.

In closing, the present novel experiment shows that it is likely that use of harmful

substances, such as drugs of abuse, would have long-lasting effects on cognition over the

lifespan stemming all the way from adolescence. Results of this longitudinal and novel

experiment would advance an area of research that is largely unexplored. Effects of drug abuse

on a long-term scale, as well as investigations into the aging population specifically with prior

adolescent substance abuse, are relatively unknown. The combination of previous research and

the present study would allow for an in-depth and lifelong investigation to a potentially

debilitating result of substance use.

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References

1. Bachi, K., Sierra, S., Volkow, N. D., Goldstein, R. Z., & Alia-Klein, N. (2017). Is

biological aging accelerated in drug addiction?. Current opinion in behavioral sciences,

13, 34–39. https://doi.org/10.1016/j.cobeha.2016.09.007

2. Chassin, L., Hussong, A., & Beltran, I. (2009). Adolescent substance use. In R. M. Lerner

& L. Steinberg (Eds.), Handbook of Adolescent Psychology: Individual Bases of

Adolescent Development (p. 723–763).

https://doi.org/10.1002/9780470479193.adlpsy001022

3. Glei D. A., Preston S. H. (2020) Estimating the impact of drug use on US mortality,

1999-2016. PLOS ONE 15(1): e0226732. https://doi.org/10.1371/journal.pone.0226732

4. Gould T. J. (2010). Addiction and cognition. Addiction Science & Clinical Practice, 5(2),

4–14.

5. Harada, C. N., Natelson Love, M. C., & Triebel, K. L. (2013). Normal cognitive aging.

Clinics in Geriatric Medicine, 29(4), 737–752. https://doi.org/10.1016/j.cger.2013.07.002

6. Hasher, L., & Zacks, R. T. (1988). Working memory, comprehension, and aging: A

review and a new view. In G. H. Bower (Ed.), The Psychology of Learning and

Motivation: Advances in Research and Theory, Vol. 22 (p. 193–225).

https://doi.org/10.1016/S0079-7421(08)60041-9

7. Kalapatapu, R. K., Ventura, M. I., & Barnes, D. E. (2017). Lifetime alcohol use and

cognitive performance in older adults. Journal of Addictive Diseases, 36(1), 38–47.

https://doi.org/10.1080/10550887.2016.1245029

8. Kelly, A. B., Evans-Whipp, T. J., Smith, R., Chan, G. C., Toumbourou, J. W., Patton, G.

C., Hemphill, S. A., Hall, W. D., & Catalano, R. F. (2015). A longitudinal study of the

Battista 15
Examining the effects of adolescent substance use on cognitive performance across the lifespan

association of adolescent polydrug use, alcohol use and high school non-completion.

Addiction (Abingdon, England), 110(4), 627–635. https://doi.org/10.1111/add.12829

9. Khurana, A., Romer, D., Betancourt, L. M., & Hurt, H. (2017). Working memory ability

and early drug use progression as predictors of adolescent substance use disorders.

Addiction (Abingdon, England), 112(7), 1220–1228. https://doi.org/10.1111/add.13792

10. Koob, G. F., & Volkow, N. D. (2010). Neurocircuitry of addiction.

Neuropsychopharmacology, 35(1), 217–238. https://doi.org/10.1038/npp.2009.110

11. Koob, G. F., & Volkow, N. D. (2016). Neurobiology of addiction: a neurocircuitry

analysis. The Lancet. Psychiatry, 3(8), 760–773. https://doi.org/10.1016/S2215-

0366(16)00104-8

12. Kuerbis, A., Sacco, P., Blazer, D. G., & Moore, A. A. (2014). Substance abuse among

older adults. Clinics in Geriatric Medicine, 30(3), 629–654.

https://doi.org/10.1016/j.cger.2014.04.008

13. Mooney-Leber, S. M., & Gould, T. J. (2018). The long-term cognitive consequences of

adolescent exposure to recreational drugs of abuse. Learning & Memory (Cold Spring

Harbor, N.Y.), 25(9), 481–491. https://doi.org/10.1101/lm.046672.117

14. Morin, J. G., Afzali, M. H., Bourque, J., Stewart, S. H., Séguin, J. R., O'Leary-Barrett,

M., & Conrod, P. J. (2019). A Population-Based Analysis of the Relationship Between

Substance Use and Adolescent Cognitive Development. The American Journal of

Psychiatry, 176(2), 98–106. https://doi.org/10.1176/appi.ajp.2018.18020202

15. Odgers, C. L., Caspi, A., Nagin, D. S., Piquero, A. R., Slutske, W. S., Milne, B. J.,

Dickson, N., Poulton, R., & Moffitt, T. E. (2008). Is it important to prevent early

Battista 16
Examining the effects of adolescent substance use on cognitive performance across the lifespan

exposure to drugs and alcohol among adolescents?. Psychological Science, 19(10), 1037–

1044. https://doi.org/10.1111/j.1467-9280.2008.02196.x

16. Ortega, A., Gómez-Ariza, C. J., Román, P., & Bajo, M. T. (2012). Memory inhibition,

aging, and the executive deficit hypothesis. Journal of Experimental Psychology:

Learning, Memory, and Cognition, 38(1), 178–186. https://doi.org/10.1037/a0024510

17. Peters R. (2006). Ageing and the brain. Postgraduate Medical Journal, 82(964), 84–88.

https://doi.org/10.1136/pgmj.2005.036665

18. Sobell, L. C., & Sobell, M. B. (1992). Timeline follow-back: A technique for assessing

self-reported alcohol consumption. In R. Z. Litten & J. P. Allen (Eds.), Measuring

Alcohol Consumption: Psychosocial and Biochemical Methods (p. 41–72).

https://doi.org/10.1007/978-1-4612-0357-5_3

19. Stroop, J. R. (1935). Studies of interference in serial verbal reactions. Journal of

Experimental Psychology, 18(6), 643–662. https://doi.org/10.1037/h0054651

20. Squeglia, L. M., Jacobus, J., & Tapert, S. F. (2009). The influence of substance use on

adolescent brain development. Clinical EEG and Neuroscience, 40(1), 31–38.

https://doi.org/10.1177/155005940904000110

21. Valeriani, M., Ranghi, F., & Giaquinto, S. (2003). The effects of aging on selective

attention to touch: a reduced inhibitory control in elderly subjects?. International Journal

of Psychophysiology: Official Journal of the International Organization of

Psychophysiology, 49(1), 75–87. https://doi.org/10.1016/s0167-8760(03)00094-1

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