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Table 1 Summary of select measures relevant to patient-reported outcomes in mild cognitive impairment

From: Patient self-report for evaluating mild cognitive impairment and prodromal Alzheimer's disease

Measure Reporter Patient population Description Psychometric performance Comments
Everyday functioning      
Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS-ADL) and ADCS ADL-MCI [47, 123] Patient, informant Mild through severe AD 23-item inventory of ADL, rated based on extent of assistance the patient requires (independently, with supervision, with physical help): 0 (total independence in performing an activity) to 4 (total inability to act independently). Each question varies in the number of options to chose. Total score range: 0 to 78; higher scores indicate less functional impairment. ADCS ADL-MCI: 18 item and 24 item versions Validity
Item content developed by a subcommittee of the ADCS Initial item pool included ADL items from existing scales and novel items based on clinical experience Items refined following pre-testing
ADCS ADL-MCI: 24 item version demonstrated superior sensitivity and specificity for aMCI discrimination from controls
Widely used, including as endpoint in clinical trials. Developed based on substantial clinical experience; comprehensive item capture
Alzheimer's Disease Cooperative Study Prevention Study (ADL-PI) [5153, 56] Patient, informant Used in mild through severe AD 20-item measure of ADLs and physical functioning. Five difficulty-based response options from 'as well as usual/no difficulty' to 'a lot of difficulty'; with 'not at all' option. Total score ranges from 0 to 45; higher scores indicate less functional impairment. Validity
Items selected based on discrimination between MCI and normal subjects Discriminated between CDR 0 and 0.5 Scores related to cognitive performance Moderate correlation of ADL-MCI patient rating with informant rating; although most scores near ceiling
Good psychometric performance; item content from established measures
     Reliability
Test-retest reliability acceptable to good (3-month interval)
 
Perceived Deficits Questionnaire (PDQ) [124] Patient Developed for multiple sclerosis; used in AD and MCI The PDQ is a part of the Multiple Sclerosis Quality of Life Inventory that assesses self-perceived cognitive difficulties. It consists of 20 items that address cognitive difficulties in four dimensions (attention/concentration, planning/organization, retrospective memory and prospective memory). Items are rated on a five-point scale ranging from 1 (never) to 5 (almost always) No psychometric data available for MCI/AD Developed for multiple sclerosis population but content relevant to MCI/AD
Multidimensional Assessment of Neurodegenerative Symptoms questionnaire (MANS) [125] Patient, informant Neurodegenerative disorders generally, early detection through more severe levels Developed as a multidimensional measure permitting early detection and patient and informant comparison and applicable from mild severity onward. Developed to measure cognitive personality, functional, and motor symptoms. Items are rated on a five-point frequency scale from 0 (never) to 4 (routinely) with Once/occasionally/more than monthly as intermediate anchors Validity
Four subscales supported by exploratory factor analysis Construct validity supported through moderate to high correlation with clinical measures
Multiple domains targeted to aid with differential diagnosis. Seeks to be gender-neutral, overcoming gender/activity confounds of other measures. Frequency scale may limit sensitivity
     Reliability
High internal consistency (alpha = 0.98) for both versions
 
Patient-Reported Outcomes in Cognitive Impairment (PROCOG)
[14]
Patient, informant MCI through moderate AD 55-item measure of cognitive impairment symptoms and their impact in patients with MCI and mild to moderate AD. There are seven subscales: affect, skill loss, semantic memory, short-term memory, cognitive functioning, social impact, and long-term memory. Items are rated on a five-point Likert scale. Total scores range from 0 to 220. Higher scores indicate greater impact of cognitive impairment Validity
Developed based on clinician input and focus groups with patients and informants
Subscale and total scores were lowest for controls and highest for AD patients, with MCI patients intermediate Highest correlations with the PROCOG were observed for the QOL-AD (r = -0.53) and CES-D (0.60)
PROCOG Affect subscale was most highly correlated to the CES-D
Correlations with the neuropsychological measures were low to moderate
MCI and DAT scores differed significantly (P ≤ 0.05 for total and subscale scores with the exception of 'social impact')
'Long-term memory' item did not distinguish among the three groups
'Skill loss' and 'memory for recent events' subscales showed the most separation between MCI and DAT patients
Acceptable psychometric properties but no longitudinal data published. Broad content mixes domain assessment; however, subscales permit more focused domain selection
     Reliability
Internal consistency: Cronbach's alpha for all subscales was above 0.82
Test-retest: no statistically significant differences across 14 day retest
ICCs ranged from 0.49 (for the single-item 'long-term memory' subscale) to 0.90
 
Mail-In Cognitive Function Screening Instrument [56] Patient   14-item brief screening instrument assessing cognitive and functional decline; prior year recall period.
Response options are 'yes' (1), 'no' (0), or 'maybe' (0.5).
Total scores range from 0 to 14; higher score indicate worse status.
Validity
Patient scores associated with clinical measures
Patient/informant core difference associated with mMMSE, NYU Paragraph immediate and delayed recall; free and cued reminder test
Trend toward relationship to APOE genotype group (none, at least one) for patient but not informant score
Brief screening measure demonstrating sensitivity to subjective memory complaints. Brevity limits comprehensiveness but for intended purpose content is appropriate
Executive functioning
Behavior Rating Inventory of Executive Function-Adult version (BRIEF-A) [68, 69]
Patient, Informant   75-item measure of executive functioning in adults composed of two index scores: the Behavioral Rating Index (BRI) and the Metacognitive Index (MI). The BRI has four subscales: inhibit, shift, emotional control, and self-monitor. The MI has five subscales: working memory, initiate, plan/organize, task monitor, and organization of materials. An overall score is obtained as a composite of two index scores. There are also three 'validity' scales used to screen for factors other than executive functioning that could explain scores on the main measure: negativity, infrequency, and inconsistency No psychometric data reported Item content targets accepted executive functioning skills
Cognitive Difficulties Scale (CDS) [126128] Patient, Informant   Multiple versions (original was 39-item self-report; 26-item version and 38-item version; family report version available). The 38-item self report version includes items related to difficulties in attention, concentration, orientation, memory, praxis, domestic activities and errands, facial recognition, task efficiency, and name finding. Items are rated on a five-point Likert scale on frequency of difficulty over prior month, from 0 (not at all) to 4 (very often) Validity
Derived and adapted from existing measures Profile of Mood States, Inventory of Psychic and Somatic Complaints, and Minnesota Multiphasic Personality Inventory Item content also based on expert clinical opinion 38-item self-report version: moderate to high correlation with performance on neuropsychological measures of memory and attention
Developed from established measures. Provides measure of anosognosia
     Reliability
Test-retest reliability acceptable in original 39-item version as well as in 26-item version
 
Everyday Cognition (ECog) [64] Patient, Informant   39-item measure of neuropsychological functioning related to cognitive impairment. Items are rated on a four-point scale: 1, better or no change compared to 10 years earlier; 2, questionable/occasionally worse; 3, consistently a little worse; 4, consistently much worse. Higher scores represent worse daily function Validity
Developed through clinical input with reference to literature; designed to address key memory and cognition symptoms that can be linked to specific neuropsychological deficits Data support six domain factors and one global factor: everyday memory, everyday language (which includes everyday semantic knowledge), everyday visuospatial abilities, and the executive domains of everyday planning, organization, and divided attention
Psychometric performance acceptable, with discrimination by clinical severity level and discrimination by different MCI subtypes
Low correlation with age and educational level (r = 0.19 and -0.16, respectively), suggestive of minimal education level bias
Convergent validity supported based on magnitude of correlation to the clinical measures and relationship to diagnostic category
Developed to minimize confound with educational level
     Reliability
Test-retest reliability was good (r = 0.82) based on 2 day to 113 day interval
 
Frontal Systems Behavior Scale (FrSBe) [71, 129] Patient, Informant Multiple therapeutic areas 46-item behavior scale rates the frontal impairments of apathy, disinhibition, and executive dysfunction, on a five-point Likert scale ranging from almost never (1) to almost always (5) for a maximum score of 240. Higher scores indicate more abnormal behavior Validity
High intrascale reliability (0.95) in normal and pathological populations, subscale reliabilities of 0.78 or higher, Adequate internal consistency reliability (Cronbach's alpha: 0.92), and construct and criterion-related validity in multiple Studies
Widely used across medical/psychiatric diseases. Captures cognitive-behavioral aspects of frontal symptoms
  1. AD, Alzheimer's disease; ADCS, Alzheimer's Disease Cooperative Study; ADL, Activities of Daily Living; ADL-PI, Activities of Daily Living Prevention Instrument; aMCI, amnestic MCI; APOE, apolipoprotein E; BRI, Behavioral Rating Index; BRIEF-A, Behavior Rating Inventory of Executive Function - Adult version; CDR, Clinical Dementia Rating scale; CDS, Cognitive Difficulties Scale; CES-D, Center for Epidemiologic Studies Depression Scale; DAT, dementia of Alzheimer's type; ICC, intra-class correlation coefficient; MCI, mild cognitive impairment; MI, Metacognitive Index; mMMSE, Modified Mini-Mental State Examination; PDQ, Perceived Deficits Questionnaire; PROCOG, Patient-Reported Outcomes in Cognitive Impairment; QOL, quality of life.