What are the possible causes of cognitive dysfunction in a 22‑year‑old female?

Causes of Cognitive Dysfunction in a 22-Year-Old Female

In a 22-year-old female presenting with cognitive dysfunction, the primary consideration should be 22q11.2 deletion syndrome if not previously diagnosed, followed by systematic evaluation for reversible causes including medication effects, psychiatric disorders (especially depression and anxiety), autoimmune/inflammatory conditions, metabolic/endocrine disorders, substance use, and infectious etiologies.

Genetic and Neurodevelopmental Causes

• 22q11.2 deletion syndrome is a critical consideration in young adults with cognitive dysfunction, as many cases remain undiagnosed until adulthood when cognitive deficits become more apparent in complex work or educational settings 1.
• Individuals with 22q11.2DS typically have verbal IQ relatively preserved compared to performance IQ, creating a "hidden disability" where deficits in executive function, working memory, arithmetic skills, and social cognition may be masked by adequate verbal abilities 1.
• Executive dysfunction manifests as impaired problem-solving, flexibility, concentration, and impulse inhibition, with literal/concrete thinking patterns 1.
• Social cognition deficits include difficulty recognizing emotions, understanding sarcasm, and interpreting others' intentions (theory of mind), increasing vulnerability to exploitation 1.

Psychiatric and Mood Disorders

• Depression is the most common potentially reversible cause of cognitive dysfunction across all age groups and should be screened systematically using validated tools like the PHQ-9 1, 2, 3.
• New-onset depression in young adults commonly presents with cognitive symptoms including difficulty thinking, concentrating, and decision-making as core DSM-5 features 1.
• Anxiety disorders frequently co-occur with cognitive complaints and should be assessed using tools like the GAD-7 2.
• Stress-related exhaustion from chronic work-related or psychosocial stress can cause decreased attention and visuospatial memory, suggesting frontal cortex/medial temporal cortex network dysfunction 4.

Medication and Substance-Related Causes

• Sedating medications including benzodiazepines (lorazepam, clonazepam, diazepam) and sedative-hypnotics (zolpidem, zaleplon, zopiclone) directly impair cognition with hazard ratios of 1.5-2.1 5, 2.
• Anticholinergic medications across multiple drug classes can cause cognitive impairment 1.
• Substance abuse including alcohol and illicit drugs (cocaine, amphetamines) are important reversible causes 1, 3.
• Medication review should be the first intervention as it represents the most immediately reversible cause 5, 2.

Autoimmune and Inflammatory Conditions

• Autoimmune encephalitis accounts for 37% of treatable causes in rapid cognitive impairment cases and should be strongly considered in young adults 6.
• Hashimoto encephalopathy (autoimmune thyroiditis with encephalopathy) is a treatable inflammatory condition that can present with cognitive dysfunction 6.
• Inflammatory demyelinating diseases including multiple sclerosis can present with cognitive symptoms as early manifestations 6.

Metabolic and Endocrine Disorders

• Hypothyroidism has a 10% prevalence in patients with cognitive complaints and should be screened with TSH and free T4 2, 6, 7.
• Vitamin B12 deficiency causes cognitive impairment with 85% sensitivity and 90% specificity when measured with methylmalonic acid and homocysteine levels 2, 6, 7.
• Folate deficiency is a less common but treatable metabolic cause 7.
• Metabolic/toxic disorders account for 5% of rapid cognitive impairment cases 6.

Infectious Causes

• Viral encephalitis accounts for 22% of treatable rapid cognitive impairment cases in young adults 6.
• Neurosyphilis should be screened with VDRL/RPR testing as a treatable infectious cause 6, 7.
• HIV-associated cognitive impairment should be considered based on risk factors 3.

Structural and Vascular Causes

• Normal pressure hydrocephalus can occur in younger adults and presents with the classic triad of cognitive impairment, gait disturbance, and urinary incontinence 6, 7.
• Space-occupying lesions including tumors account for 12% of rapid cognitive impairment cases 6, 3.
• Chronic subdural hematoma should be considered with any history of head trauma 7.
• Vascular diseases including stroke or cerebral vasculitis account for 22% of rapid cognitive impairment cases 6.

Sleep Disorders

• Obstructive sleep apnea causes cognitive impairment through chronic hypoxemia and sleep fragmentation 1.
• Sleep disturbances and fatigue negatively affect cognitive functioning independent of other causes 1.

Hormonal and Reproductive Factors

• Oral contraceptive hormones can contribute to cognitive symptoms in some women 1.
• Sex differences in cognitive performance exist, with females typically outperforming males in verbal tasks but showing different patterns in spatial tasks 8.

Critical Diagnostic Approach

Immediate laboratory workup should include: TSH, free T4, vitamin B12, folate, methylmalonic acid, homocysteine, CBC, comprehensive metabolic panel, VDRL/RPR, and HIV testing 2, 6, 7.

Neuroimaging with brain MRI (preferred over CT) is indicated for cognitive symptoms with recent onset, rapid decline, unexplained neurological signs, or age less than 60 years 2.

Structured cognitive assessment using the Montreal Cognitive Assessment (MoCA) provides 90% sensitivity for detecting cognitive impairment compared to 75% for MMSE 2.

Collateral history from a reliable informant is mandatory, providing 80% sensitivity and 90% specificity for detecting cognitive impairment 2.

Common Pitfalls to Avoid

• Never attribute cognitive symptoms to "normal aging" in a 22-year-old without comprehensive workup, as 72% of rapid cognitive impairment cases have treatable causes 6.
• Never overlook medication effects as the most immediately reversible cause—review and discontinue all cognitively impairing medications first 5, 2.
• Never ignore psychiatric symptoms, as depression and anxiety are highly prevalent, treatable causes that frequently present with cognitive complaints 1, 2.
• Never delay vitamin B12 replacement while waiting for test results if clinical suspicion is high, as this can lead to irreversible neurologic damage 2.
• Never assume cognitive symptoms are purely functional without excluding autoimmune/inflammatory conditions, which account for 37% of treatable rapid cognitive impairment cases in young adults 6.