Subjective Cognitive Concerns and Neuropsychiatric Predictors of Progression to the Early Clinical Stages of Alzheimer Disease

Abstract

Objectives To examine neuropsychiatric and neuropsychological predictors of progression from normal to early clinical stages of Alzheimer’s disease (AD). Design Longitudinal study Setting Massachusetts Alzheimer’s Disease Research Center longitudinal cohort Participants From a total sample of 559 older adults, 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. Measurements 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 (HR=0.4 for one 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 4-fold risk of progression compared to CN (HR=4.1, p<0.0001). Conclusions 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.

Predictors of Clinical Progression of Subjective Memory Impairment in Elderly Subjects: Data from the Clinical Research Centers for Dementia of South Korea (CREDOS)

“…A recent study compared baseline characteristics of progressing and non-progressing SMI subjects and reported that progressing subjects were older and had more AD biomarkers in the cerebrospinal fluid [6] . Another study reported that SMI subjects with APOE4 had a higher amyloid deposition, suggesting preclinical AD [16] . A cohort study composed of normal elderly and patients with subjective cognitive impairment and MCI reported that low scores in memory, naming, and semantic fluency predicted rapid progression across all groups [17] .…”

From Subjective Cognitive Complaints to Dementia

“…Subjective cognitive complaints, loss, or impairment were defined in 5 studies 17,21,22,24,25 by a positive answer to any of 2 questions: ''do you feel like your memory is becoming worse'' or ''do you have problems with your memory.'' One study used both informant-based and selfbased reports to define SMC, 18 and another identified 4 groups based on investigator judgment during an interview: no complaints, self-complaints, and informant complaints in the absence or in the presence of self-complaints. 19 A positive score on the Multidimensional Assessment of Neurodegenerative Symptoms was used as a definition of cognitive complaint by the last one.…”

Depressive Symptoms and Biomarkers of Alzheimer’s Disease in Cognitively Normal Older Adults

“…[1–3] While chronic late life major depression (LLD) confers the greatest risk of transition to MCI[3], other forms of depression, such as intermittent and remitted major depression[3], or low-grade depressive symptoms measured by depression screening instruments[4] or as a neuropsychiatric symptom item[1, 3] are also associated with increased risk of cognitive decline in older individuals without objective cognitive impairment. Here, the term “subthreshold symptoms of depression” (SSD) is used to encompass lower severity depressive classifications that do not meet diagnostic criteria for major depression, such as subsyndromal depression and minor depression, as well as depressive symptoms within a low or subclinical range on depression scales.…”