Alzheimer's Disease Neuroimaging Initiative 4

This is a measure of verbal fluency in which the participant is asked to generate examples from the semantic categories (animals) in successive one-minute trials

Everyday Cognition (ECog) is a brief questionnaire assessing the participant's capability to perform normal everyday tasks, in comparison to activity levels at their own understanding of their prior baseline, using a 5-point scale. Previous research on this instrument indicates that ECog correlates well with established measures of functional status and global cognition but only weakly with age and education. ADNI4 will use the 12-item ECog with language updates from Farias et al. 2021 meant to improve generalizability across diverse groups.

We will use a modified episodic memory measure from the Wechsler Memory Scale- Revised (WMS-R) 24. In this modified version, free recall of one short story will be elicited immediately after it is read aloud to the participant and again after a thirty-minute delay

The Montreal Cognitive Assessment test (MoCA) is, similar to the MMSE, a brief, 30- point cognitive assessment designed to detect participants at the MCI stage of cognitive dysfunction. This instrument has been shown to have adequate sensitivity and specificity in clinical settings to detect suspected MCI. The performance of the MoCA will be followed to determine its ability to differentiate among the three diagnostic groups in ADNI4

The Multilingual Naming Test (MINT) is a test of object picture naming designed to include items that are comparable across English, Spanish, Mandarin and Hebrew. It replaces the Boston Naming Test (BNT) in the Uniform Data Set of the NIA- funded Alzheimer's Disease Centers because the BNT contains items that are not of the same level of difficulty for Spanish- and English-speakers

An important consideration in measuring cognition is current stress. Research suggests that current perceived stress can affect neurocognitive functioning (Lupien et al., 2009). Thus, measuring current stress in the present study is an important element of study procedures. The PSS measures current stress levels and stressful experiences in the last month. It asks about experiences such as feeling in control of one's life, feeling the ability to be productive, feeling overwhelmed, and being upset by unexpected events (Cohen, Kamarck, \& Mermelstein, 1983). These items are rated on a Likert scale of 1-5, with 1 representing "Almost Always" and 5 representing "Almost Never." In scoring, the scale is reverse coded where appropriate, such that a low score is indicative of a lower level of perceived stress.

The AVLT is a list-learning task, which assesses multiple cognitive parameters associated with learning and memory.

These two tests progress from a numerical connect-the-dots puzzle to a more challenging alternation between alpha- and numerical order. Although both Parts A and B depend on visuomotor and perceptual-scanning skills, Part B also requires considerable cognitive flexibility in shifting from number to letter sets under time pressure.

The Clinical Dementia Rating (CDR) describes five degrees of impairment in performance on each of 6 categories of cognitive functioning including memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. Impairment is scored on a scale in which none = 0, questionable = 0.5, mild = 1, moderate = 2 and severe = 3. A higher score indicates more impairment.

Based on an interview with a caregiver or qualified partner, a participant is rated on his/her ability to carry out ten complex activities of daily living.

The Neuropsychiatric Inventory (NPI) is a well-validated, reliable, multi-item instrument to assess psychopathology in AD based on an interview with a caregiver or qualified study partner. The NPI evaluates both the frequency and severity of 12 neuropsychiatric features, including: delusions, hallucinations, agitation/aggression, dysphoria, anxiety, euphoria, apathy, disinhibition, irritability/lability, aberrant motor behavior, sleep and appetite/eating disorders.

Frequency assessments range from 1 (occasionally, less than once per week) to 4 (very frequent, continuously present); severity from 1(mild), 2 (moderate) and 3 (severe) and distress from 0 (no distress) to 5 (very severe/extreme distress). For each behavioral domain, there are 4 scores: frequency, severity, domain score (frequency x severity) and caregiver distress. The total score is the sum of all domain scores. The distress score is not included in the total NPI score.

The Neuropsychiatric Inventory Q was designed as a version of the Neuropsychiatric Inventory (NPI) that could be administered more quickly and over the telephone. The NPI-Q measures the burden of 12 neuropsychiatric symptoms of dementia: delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability/lability, motor disturbance, nighttime behaviors, and appetite/eating.

Frequency assessments range from 1 (occasionally, less than once per week) to 4 (very frequent, continuously present); severity from 1(mild), 2 (moderate) and 3 (severe) and distress from 0 (no distress) to 5 (very severe/extreme distress). For each behavioral domain, there are 4 scores: frequency, severity, domain score (frequency x severity) and caregiver distress. The total score is the sum of all domain scores. The distress score is not included in the total NPI score.

The GDS Short Form is a self-report scale designed to screen for symptoms of depression in the elderly. The assessment is administered by clinic personnel to the study participant and consists of 15 questions that the participant is asked to answer yes or no on the basis of how they felt over the past week. Answers to 5 of the items are negatively oriented for depression (e.g., Do you feel full of energy?) and 10 positively oriented (e.g., Do you often feel helpless?). One point is given for each appropriate positive or negative answer indicative of a symptom of depression, for a possible total of 15 points. Although differing sensitivities and specificities have been obtained across studies, for clinical purposes a total score of 0-5 are considered likely to be normal and scores of 6-15 are considered to be more likely to be depressed.

Cerebrospinal fluid (CSF) samples will be used to measure the levels of amyloid β-peptide (Aβ) 40. CSF Aβ40 is a key Alzheimer's disease (AD) biomarker that reflects pathological aggregation of amyloid in the brain.

Cerebrospinal fluid (CSF) samples will be used to measure the levels of amyloid β-peptide (Aβ) 42. CSF Aβ42 is a key Alzheimer's disease (AD) biomarker that reflects pathological aggregation of amyloid in the brain.

Cerebrospinal fluid (CSF) samples will be used to measure the levels of total tau protein in the brain to assess impact on brain tau as a relevant Alzheimer's Disease (AD) biomarker.

Cerebrospinal fluid (CSF) samples will be used to measure the levels of phospho-tau 181 protein in the brain to assess impact on brain tau as a relevant Alzheimer's Disease (AD) biomarker.