Cognitive Training and Neuroplasticity in Mild Cognitive Impairment

Inclusion Criteria

• Males and females 55 to 95 years of age (inclusive) at the time of informed consent.
• Subjective cognitive complaints, i.e., memory or other cognitive complaints, e.g., naming/language.
• Meets criteria for cognitive impairment defined as scores > 1 below standardized norms on memory function as identified by the Wechsler Memory Scale (WMS) III Logical Memory immediate or delayed recall score.
• Folstein Mini Mental State score ≥ 23 out of 30.
• A family member or other individual who is in contact with the patient and consents to serve as informant during the study; this can be a telephone informant in the case of patients who do not have a live-in informant or close significant other.
• Access to a home desktop or laptop computer at acceptable internet speed for the study duration.

Exclusion Criteria

• Diagnosis of dementia of any type.
• Current clinical evidence of schizophrenia, schizoaffective disorder, major depression, psychosis, or bipolar I disorder (DSM-IV criteria).
• Active suicidal ideation or plan.
• Current or recent (past 6 months) alcohol or substance use disorder (DSM-5 criteria).
• Clinical stroke with residual neurological deficits. While we will not exclude patients with cerebrovascular disease, we will not include patients who have had a stroke with residual clinical deficits because it is not clear that this type of patient is similar to the MCI (Mild Cognitive Impairment) patient generally, and clear-cut neurological impairment, e.g., hemiplegia/hemiparesis or speech impairment, may compromise the patient's ability to do the CCT or active control procedures and to complete the neuropsychological test battery.
• Use of medications known to have a negative impact on cognition: benzodiazepines in lorazepam equivalents greater than or equal to 1 mg daily, narcotics, anticholinergics. Other patients receive medications that may be associated with cognitive impairment but are rarely considered the likely etiology, e.g., theophylline, nifedipine, beta blockers; they will not be excluded. Patients receiving other psychotropic medications not expected to have a material impact on cognition, e.g., SSRIs (Selective Serotonin Re-uptake Inhibitors) and SNRIs (Serotonin-norepinephrine re-uptake inhibitors) will be eligible.
• Presence of any of the following disorders: a) Central Nervous System infection, with cerebrospinal fluid evidence of meningitis, encephalitis, or other infectious process; b) dementia of any type; c) Huntington's disease; d) Multiple sclerosis; e) Parkinson's disease; f) Other neurologic disorders with focal signs, e.g., amyotrophic lateral sclerosis; g) Mental retardation.
• Acute, severe unstable medical illness. For cancer, acutely ill patients (including those with metastases) will be excluded, but past history of successfully treated cancer will not result in exclusion.
• Contraindication to MRI scan: pacemaker, metal implants following surgery, any other contraindication to MRI. Eligibility for the MRI scan is a requirement for the study.
• UPSIT (University of Pennsylvania Smell Identification Test) exclusions: current smoker > 1 pack daily, current upper respiratory infection (retested as soon as the infection clears). UPSIT scores are reduced in schizophrenia, Parkinson's disease and Parkinson's related conditions; these disorders are exclusion criteria for this study. Patients with UPSIT exclusions, e.g., current heavy smoker (less than 3% of older adults in our experience), will not receive the UPSIT but will continue to participate in all other aspects of the study.
• Patients lacking English-speaking ability as determined by self-report and clinical evaluation.
• Regular online brain training or regular crossword puzzle user, defined as doing these procedures at a frequency of twice weekly or greater during the year prior to screening. Eligible participants who join the trial are instructed not to do these procedures on their own dur