Locke, Dona E C

Background Mild cognitive impairment (MCI) represents a critical window for both pharmacological therapies and non-pharmacological interventions to delay cognitive decline. Objective To evaluate whether combining pharmacotherapy with multicomponent behavioral interventions enhances outcomes relative to behavioral interventions alone. Methods The sample included people with MCI (pwMCI) of any etiology who completed the HABIT Healthy Action to Benefit Independence & Thinking ® program. Baseline pharmacotherapy (acetylcholinesterase inhibitor and/or glutamate regulators) use was dichotomized (yes/no). Multivariate linear mixed-effects models examined changes from baseline in care partner-reported everyday functional skills, quality of life, self-efficacy, anxiety, depression, and HABIT compliance at post-intervention, 6 months, and 12 months, adjusting for baseline cognitive impairment severity and relevant demographic covariates. Results Among 1074 pwMCI, 413 (38.5%) were receiving pharmacotherapy at baseline. Pharmacotherapy use was more prevalent among White than non-White participants (39.4% versus 23.3%, p = 0.01). At baseline, pharmacotherapy users had more severe cognitive impairment and lower utilization of rehabilitation strategies (all p < 0.05). Both groups demonstrated significant improvements across all outcomes at post-intervention. During follow-up (mean score change compared to baseline), pharmacotherapy users showed greater increases in HABIT compliance at 6 months (3.2 versus 2.0) and 12 months (2.1 versus 1.4). In contrast, by 12 months, pharmacotherapy users experienced greater worsening of everyday functional skills related to memory (−2.1 versus −1.3) and executive function (−5.8 versus-3.7). Conclusions pwMCI undergoing pharmacotherapy entered the HABIT program with more advanced cognitive impairment. The pharmacotherapy was not associated with greater intervention-related benefit or attenuation of long-term cognitive decline.

Background: Mild cognitive impairment (MCI) is a precursor to dementia, with a prevalence of over 15% among community dwellers, with significant economic and social implications. Despite preserved autonomy in daily living, individuals with MCI face challenges in handling everyday technology and memory-related tasks, necessitating digital interventions, such as digital planning-based technologies to support cognitive functioning. Objective: The aim of this study is to identify and summarize available research literature on available digital planning-based technologies to support memory-related functioning in older adults with MCI. Specifically, this study seeks to (1) document the types and functions of these technologies, (2) report their effectiveness, and (3) identify gaps in the current evidence. Methods: A comprehensive literature search of four databases (Medline, Embase, APA PsycINFO, and CINAHL) was conducted in accordance with Arksey and O’Malley’s scoping review methodological framework from inception to February 6, 2024, without restrictions. Inclusion criteria focused on peer-reviewed studies involving adults aged 50 or older with diagnosed cognitive impairment, specifically using digital planning-based technologies for memory support. Results: From 1854 sources, 8 studies were included. Five categories of digital planning-based technologies were identified: (1) reminders and alarms, (2) electronic calendars, (3) digital memory notebooks, (4) digital visual mapping, and (5) smart-home integration. Several studies reported improved task performance, memory recall, and executive function, with digital memory notebooks and visual mapping software showing greatest impact on functional independence. While interventions were generally well-received, usability challenges and low adherence were common, often linked to technological familiarity and motivation. Conclusions: Digital planning-based technologies show promise in supporting memory-related functioning in older adults with MCI. While studies report positive outcomes, more research is needed to refine these tools, evaluate long-term effects, and ensure integration into daily life. Expanding the evidence base will be key to improving accessibility and effectiveness for this population.

AbstractINTRODUCTIONWe previously demonstrated that single‐domain amnestic mild cognitive impairment (SDAm‐MCI) detected through longitudinal neuropsychological testing in our research cohort is less severe than in clinically incident symptomatic individuals. This study aims to replicate and expand this work using a National Alzheimer's Coordinating Center dataset.METHODSParticipants were classified into two groups: those enrolled with normal cognition (Normal Enrollees) and those enrolled with SDAm‐MCI (Amnestic Enrollees). Groups were compared at the time of diagnosis and on rates of cognitive decline post‐diagnosis.RESULTSAt SDAm‐MCI diagnosis, Normal Enrollees were 17% to 39% less impaired on memory tasks, after which the slope of change over time steepened compared to their pre‐symptomatic change and was steeper than in Amnestic Enrollees.DISCUSSIONIncident MCI detected through longitudinal neuropsychological testing is initially milder but may progress more steeply than in clinically established MCI. Sensitive assessment of cognitive decline is essential for capturing early changes that are more likely to be amenable to therapeutic treatment.Highlights Longitudinal cognitive evaluation detects symptomatic Alzheimer's disease earlier than mental status exams. At the time of diagnosis, converters were less impaired compared to initially symptomatic patients. Converters’ cognition declined more steeply than initially symptomatic patients. Sensitive cognitive tests are essential to capture early changes, given new disease‐modifying therapies.

AbstractBackgroundIt is not known whether preclinical cognitive decline is associated with fibrillar β‐amyloid (Aβ) deposition irrespective of apolipoprotein E (APOE) ε4 status.MethodsFrom a prospective observational study of 623 cognitively normal individuals, we identified all subjects who showed preclinical decline of at least 2 standard deviations beyond the decline of the entire group in memory or executive function. Fourteen decliners were matched by APOE ε4 gene dose, age, sex, and education with 14 nondecliners. Dynamic Pittsburgh compound B (PiB) positron emission tomography (PET) scans, the Logan method, statistical parametric mapping, and automatically labeled regions of interest were used to characterize and compare cerebral‐to‐cerebellar PiB distribution volume ratios (DVRs), reflecting fibrillar Aβ burden.ResultsAt P < .005 (uncorrected), decliners had significantly greater DVRs in comparison to nondecliners.ConclusionsAsymptomatic longitudinal neuropsychological decline is associated with subsequent increased fibrillar amyloid deposition, even when controlling for APOE ε4 genotype.

AbstractBackgroundIt is unclear whether self‐ or informant‐based subjective cognition better distinguishes emotional factors from early‐stage Alzheimer's disease (AD).MethodsHealthy members (n = 447) of the Arizona apolipoprotein E (APOE) cohort and their informants completed the self and informant paired Multidimensional Assessment of Neurodegenerative Symptoms questionnaire (MANS).ResultsDecline on the MANS was endorsed by 30.6% of members and 26.2% of informants. Self‐ and informant‐based decliners had higher scores of psychological distress and slightly lower cognitive scores than nondecliners. Over the next 6.7 years, 20 developed mild cognitive impairment (MCI). Converters were older at entry than nonconverters (63.8 [7.0] vs 58.8 [7.3] years, P = .003), 85% were APOE ε4 carriers (P < .0001), and they self‐endorsed decline earlier than informants (58.9 [39.2] vs 28.0 [40.4] months before MCI; P = .002).ConclusionsSelf‐ and informant‐based subjective decline correlated with greater psychological distress and slightly lower cognitive performance. Those with incident MCI generally self‐endorsed decline earlier than informants.

AbstractObjectiveA National Institute on Aging–sponsored work group on preclinical Alzheimer's disease (AD) articulated the need to characterize cognitive differences between normal aging and preclinical AD.MethodsSeventy‐one apolipoprotein E (APOE) ε4 homozygotes, 194 ε3/ε4 heterozygotes, and 356 ε4 noncarriers age 21 to 87 years who were cognitively healthy underwent neuropsychological testing every 2 years. Longitudinal trajectories of test scores were compared between APOE subgroups.ResultsThere was a significant effect of age on all cognitive domains in both APOE ε4 carriers and noncarriers. A significant effect of APOE ε4 gene dose was confined to the memory domain and the Dementia Rating Scale. Cross‐sectional comparisons did not discriminate the groups.ConclusionsAlthough cognitive aging patterns are similar in APOE ε4 carriers and noncarriers, preclinical AD is characterized by a significant ε4 gene dose effect that impacts memory and is detectable longitudinally. Preclinical neuropsychological testing strategies should emphasize memory‐sensitive measures and longitudinal design.