Subjective cognitive concerns and neuropsychiatric predictors of progression to the early clinical stages of Alzheimer disease.

OBJECTIVE: To examine neuropsychiatric and neuropsychological predictors of progression from normal to early clinical stages of Alzheimer disease (AD). METHODS: From a total sample of 559 older adults from the Massachusetts Alzheimer's Disease Research Center longitudinal cohort, 454 were included in the primary analysis: 283 with clinically normal cognition (CN), 115 with mild cognitive impairment (MCI), and 56 with subjective cognitive concerns (SCC) but no objective impairment, a proposed transitional group between CN and MCI. Two latent cognitive factors (memory-semantic, attention-executive) and two neuropsychiatric factors (affective, psychotic) were derived from the Alzheimer's Disease Centers' Uniform Data Set neuropsychological battery and Neuropsychiatric Inventory brief questionnaire. Factors were analyzed as predictors of time to progression to a worse diagnosis using a Cox proportional hazards regression model with backward elimination. Covariates included baseline diagnosis, gender, age, education, prior depression, antidepressant medication, symptom duration, and interaction terms. RESULTS: Higher/better memory-semantic factor score predicted lower hazard of progression (hazard ratio [HR] = 0.4 for 1 standard deviation [SD] increase, p <0.0001), and higher/worse affective factor score predicted higher hazard (HR = 1.3 for one SD increase, p = 0.01). No other predictors were significant in adjusted analyses. Using diagnosis as a sole predictor of transition to MCI, the SCC diagnosis carried a fourfold risk of progression compared with CN (HR = 4.1, p <0.0001). CONCLUSION: These results identify affective and memory-semantic factors as significant predictors of more rapid progression from normal to early stages of cognitive decline and highlight the subgroup of cognitively normal elderly with SCC as those with elevated risk of progression to MCI.

Functional Activities Questionnaire Items that Best Discriminate and Predict Progression from Clinically Normal to Mild Cognitive Impairment.

BACKGROUND: Impairment in instrumental activities of daily living (IADL) emerges in the transition from mild cognitive impairment (MCI) to Alzheimer's disease (AD) dementia. Some IADL scales are sensitive to early deficits in MCI, but none have been validated for detecting subtle functional changes in clinically normal (CN) elderly at risk for AD. METHODS: Data from 624 subjects participating in the Alzheimer's Disease Neuroimaging Initiative and 524 subjects participating in the Massachusetts Alzheimer's Disease Research Center, which are two large cohorts including CN elderly and MCI subjects, were used to determine which Functional Activities Questionnaire items best discriminate between and predict progression from CN to MCI. RESULTS: We found that "Remembering appointments" and "assembling tax records" best discriminated between CN and MCI subjects, while worse performance on "paying attention and understanding a TV program", "paying bills/balancing checkbook", and "heating water and turning off the stove" predicted greater hazard of progressing from a diagnosis of CN to MCI. CONCLUSIONS: These results demonstrate that certain questions are especially sensitive in detecting the earliest functional changes in CN elderly at risk for AD. As the field moves toward earlier intervention in preclinical AD, it is important to determine which IADL changes can be detected at that stage and track decline over time.

Everyday cognition scale items that best discriminate between and predict progression from clinically normal to mild cognitive impairment.

BACKGROUND: Impairment in instrumental activities of daily living (IADL) starts as individuals with amnestic mild cognitive impairment (MCI) transition to Alzheimer's disease (AD) dementia. However, most IADL scales have not shown IADL alterations in clinically normal (CN) elderly. The objective of this study was to determine which of the IADL-related Everyday Cognition (ECog) scale items are most sensitive for detection of early functional changes. METHODS: We assessed 290 CN and 495 MCI participants from the Alzheimer's Disease Neuroimaging Initiative. We performed logistic regression analyses predicting the probability of CN vs. MCI diagnosis using only the 17 participant-based and 17 informant-based ECog items related to IADL. We then performed Cox regression analyses to predict progression from CN to MCI. All analyses were adjusted for demographic characteristics. RESULTS: We found that worse performance on "remembering a few shopping items" (participant and informant-based p<0.0001), "remembering appointments" (participant and informant-based p<0.0001), "developing a schedule in advance of anticipated events" (participant-based p=0.007), "balancing checkbook" (participant-based p=0.02), and "keeping mail and papers organized" (informant-based p=0.002) best discriminated MCI from CN. We found that worse performance on "keeping mail and papers organized" (participant-based Hazard Ratio (HR)=2.27, p=0.07) marginally predicted greater hazard of progressing from CN to MCI. CONCLUSIONS: Our results indicate that a few simple questions targeting early functional changes, addressed either to the individual or informant, can effectively distinguish between CN elderly and individuals with MCI. Additionally, one of the above questions related to organization suggested which CN individuals are likely to progress to MCI.

SIST-M-IR activities of daily living items that best discriminate clinically normal elderly from those with mild cognitive impairment.

BACKGROUND: Activities of daily living (ADL) impairment is a hallmark of Alzheimer's disease (AD) dementia, but impairment in instrumental ADL (IADL) has been reported in mild cognitive impairment (MCI). The Structured Interview and Scoring Tool-Massachusetts Alzheimer's Disease Research Center (MADRC)-Informant Report (SIST-MIR) includes 60 graded items that assist in scoring the Clinical Dementia Rating; it assesses the spectrum of cognitive and ADL changes relevant to early AD. Of the 60 SIST-M-IR items, 41 address IADL; we aimed to determine which of these best discriminate individuals with MCI from clinically normal (CN) elderly. METHODS: We assessed 447 subjects participating in the MADRC longitudinal cohort (289 CN, 158 MCI). We performed logistic regression analyses predicting the probability of CN vs. MCI diagnosis using the SIST-M-IR items. Analyses were adjusted for demographic characteristics. RESULTS: We found that 4 SIST-M-IR items best discriminated between CN and MCI subjects (MCI performing worse than CN): "participating in games that involve retrieving words" (p=0.0001), "navigating to unfamiliar areas" (p=0.001), "performing mental tasks involved in a former primary job" (p=0.002), and "fixing things or finishing projects" (p=0.002). CONCLUSIONS: Our results point to the earliest functional changes seen in elderly at risk for AD, which could be captured by a few simple questions. Honing the sensitivity of clinical assessment tools will help clinicians differentiate those individuals with normal aging from those who are developing cognitive impairment.