Mild behavioral impairment (MBI) is a construct that describes the emergence at ≥50 years of age of sustained and impactful neuropsychiatric symptoms (NPS), as a precursor to cognitive decline and ...dementia. MBI describes NPS of any severity, which are not captured by traditional psychiatric nosology, persist for at least 6 months, and occur in advance of or in concert with mild cognitive impairment. While the detection and description of MBI has been operationalized in the International Society to Advance Alzheimer's Research and Treatment - Alzheimer's Association (ISTAART-AA) research diagnostic criteria, there is no instrument that accurately reflects MBI as described.
To develop an instrument based on ISTAART-AA MBI criteria.
Eighteen subject matter experts participated in development using a modified Delphi process. An iterative process ensured items reflected the five MBI domains of 1) decreased motivation; 2) emotional dysregulation; 3) impulse dyscontrol; 4) social inappropriateness; and 5) abnormal perception or thought content. Instrument language was developed a priori to pertain to non-demented functionally independent older adults.
We present the Mild Behavioral Impairment Checklist (MBI-C), a 34-item instrument, which can easily be completed by a patient, close informant, or clinician.
The MBI-C provides the first measure specifically developed to assess the MBI construct as explicitly described in the criteria. Its utility lies in MBI case detection, and monitoring the emergence of MBI symptoms and domains over time. Studies are required to determine the prognostic value of MBI for dementia development, and for predicting different dementia subtypes.
Frontotemporal dementia (FTD) is a highly heritable condition with multiple genetic causes. In this study, similarities and differences of gray matter (GM) atrophy patterns were assessed among 3 ...common forms of genetic FTD (mutations in C9orf72, GRN, and MAPT). Participants from the Genetic FTD Initiative (GENFI) cohort with a suitable volumetric T1 magnetic resonance imaging scan were included (319): 144 nonmutation carriers, 128 presymptomatic mutation carriers, and 47 clinically affected mutation carriers. Cross-sectional differences in GM volume between noncarriers and carriers were analyzed using voxel-based morphometry. In the affected carriers, each genetic mutation group exhibited unique areas of atrophy but also a shared network involving the insula, orbitofrontal lobe, and anterior cingulate. Presymptomatic GM atrophy was observed particularly in the thalamus and cerebellum in the C9orf72 group, the anterior and medial temporal lobes in MAPT, and the posterior frontal and parietal lobes as well as striatum in GRN. Across all presymptomatic carriers, there were significant decreases in the anterior insula. These results suggest that although there are important differences in atrophy patterns for each group (which can be seen presymptomatically), there are also similarities (a fronto-insula-anterior cingulate network) that help explain the clinical commonalities of the disease.
•Functional connectivity changes are present in individuals with AD-risk factors.•The topography shows an overlap with regions characteristic for AD.•Less consensus on the directionality of ...functional connectivity changes.
Functional brain connectivity of the resting-state networks has gained recent attention as a possible biomarker of Alzheimer’s Disease (AD). In this paper, we review the literature of functional connectivity differences in young adults and middle-aged cognitively intact individuals with non-modifiable risk factors of AD (n = 17). We focus on three main intrinsic resting-state networks: The Default Mode network, Executive network, and the Salience network. Overall, the evidence from the literature indicated early vulnerability of functional connectivity across different at-risk groups, particularly in the Default Mode Network. While there was little consensus on the interpretation on directionality, the topography of the findings showed frequent overlap across studies, especially in regions that are characteristic of AD (i.e., precuneus, posterior cingulate cortex, and medial prefrontal cortex areas). We conclude that while resting-state functional connectivity markers have great potential to identify at-risk individuals, implementing more data-driven approaches, further longitudinal and cross-validation studies, and the analysis of greater sample sizes are likely to be necessary to fully establish the effectivity and utility of resting-state network-based analyses.
The hippocampus is one of the first regions to demonstrate atrophy during the prodromal stage of Alzheimer's disease. Volumetric analysis of its individual subfields could provide biomarkers with ...higher sensitivity than whole hippocampal volume during an earlier disease stage. We quantified the hippocampal subfields volume in a large cohort comprising healthy participants (aged 40–59) with dementia family history (FH) and controls (without FH), examined at 2 time points across 2 years. Subfield volumes were quantified using both a T1-weighted and a high-resolution T2 hippocampal magnetic resonance imaging acquisition with Freesurfer. The participants were stratified based on dementia FH, APOE genotype, and CAIDE (Cardiovascular Risk Factors, Aging and Dementia) risk score. Whole hippocampal volume did not differ between the groups. The volume of the molecular layer was lower in participants with an APOE ε4 genotype, but there were no differences between subjects with and without dementia FH or with an increasing CAIDE score. The molecular layer may be the first hippocampal region to demonstrate volumetric alterations in subjects at risk of dementia.
•Serial hippocampal subfield volumetry was performed in the PREVENT-Dementia study.•The molecular layer volume was lower in participants with an APOE ε4 genotype.•This finding was recorded in the absence of whole hippocampal atrophy.•The molecular layer might be the first subfield to demonstrate pathological alterations in Alzheimer's disease.•Hippocampal subfield atrophy in Alzheimer's disease might precede whole hippocampal atrophy.
Motoric cognitive risk syndrome (MCR) is a predementia condition that combines slow gait speed and subjective cognitive concerns (SCC). The SCC criterion is presently unstandardized, possibly ...limiting risk detection. We sought to (a) characterize SCC practices through MCR literature review; (b) investigate the ability of SCC in slow gait individuals in predicting the likelihood of cognitive impairment in a demographically diverse sample of community-dwelling, nondemented older adults.
First, we comprehensively reviewed the MCR literature, extracting information regarding SCC measures, items, sources, and cognitive domain. Next, Einstein Aging Study (EAS) participants (N = 278, Mage = 77.22 ± 4.74, %female = 67, Meducation = 15 ± 3.61, %non-Hispanic White = 46.3) completed gait, Clinical Dementia Rating Scale (CDR), and SCC assessment at baseline and annual follow-up (Mfollow-up = 3.5). Forty-two participants met slow gait criteria at baseline. Generalized linear mixed-effects models examined baseline SCC to predict cognitive impairment on CDR over follow-up.
We reviewed all published MCR studies (N = 106) and documented ambiguity in SCC criteria, with a prevalent approach being use of a single self-reported memory item. In EAS, high SCC endorsement on a comprehensive, validated screen significantly affected the rate of cognitive impairment (CDR; βinteraction = 0.039, p = .018) in slow gait individuals.
An assessment approach that queries across numerous SCC domains was found to predict future decline in clinical dementia status in slow gait older adults. Current SCC practices in MCR, which tend to utilize a single-memory item, may not be the optimal approach. We discuss the implications of SCC criteria validation and standardization to enhance early dementia detection in MCR.
Objective: We investigated whether vascular risk factors (VRFs), assessed with Life's Simple 7 (LS7), are associated with the rate of cognitive decline in the years preceding a dementia diagnosis. ...Method: This study included 1,449 stroke-free participants aged ≥60 years from the Swedish National Study on Aging and Care in Kungsholmen, who underwent repeated neuropsychological testing (episodic memory, semantic memory, verbal fluency, perceptual speed) across 12 years. The LS7 score, assessed at baseline, included smoking, diet, physical activity, body mass index, plasma glucose, total cholesterol, and blood pressure. Preclinical dementia was defined as being dementia-free at baseline and diagnosed with dementia during follow-up. Level and change in cognitive performance as a function of LS7 category (poor vs. intermediate to optimal) and future dementia status were estimated using linear mixed-effect models. Results: Participants who later developed dementia had, on average, a poorer LS7 score compared to those who remained dementia-free. For individuals aged 60-72 years, poor diet was associated with accelerated decline in perceptual speed (β = −0.05, 95% CI −0.08, −0.02), and a poor glucose score was associated with faster rates of verbal fluency (β = −0.019, 95% CI −0.09, −0.01) and global cognitive (β = −0.028, 95% CI −0.06, 0.00) decline in the preclinical dementia group. Conclusions: VRFs exacerbate rate of cognitive decline in the years preceding a dementia diagnosis. This effect was most pronounced in young-old age and primarily driven by diet and glucose. The effect of VRFs may be especially detrimental for cognitive decline trajectories of individuals with impending dementia.
Key Points
Question: This study investigated whether vascular risk factors (smoking, diet, physical activity, body mass index, plasma glucose, total serum cholesterol, and blood pressure) are associated with accelerated cognitive decline in the preclinical dementia phase. Findings: The results indicated that poor cardiovascular health might be associated with further acceleration of cognitive decline in the years preceding a dementia diagnosis. Importance: The preclinical dementia stage could be the last opportunity to influence the rate of cognitive decline by altering vascular risk factors. Next Steps: Future studies should investigate the extent to which management of VRFs in individuals at increased risk of dementia may slow down cognitive decline.
Wearable digital technologies capable of measuring everyday behaviors could improve the early detection of dementia‐causing diseases. We conducted two systematic reviews following Preferred Reporting ...Items for Systematic reviews and Meta‐Analyses (PRISMA) guidelines to establish the evidence base for measuring navigation and gait, two everyday behaviors affected early in AD and non‐AD disorders and not adequately measured in current practice. PubMed and Web of Science databases were searched for studies on asymptomatic and early‐stage symptomatic individuals at risk of dementia, with the Newcastle–Ottawa Scale used to assess bias and evaluate methodological quality. Of 316 navigation and 2086 gait records identified, 27 and 83, respectively, were included in the final sample. We highlight several measures that may identify at‐risk individuals, whose quantifiability with different devices mitigates the risk of future technological obsolescence. Beyond navigation and gait, this review also provides the framework for evaluating the evidence base for future digital measures of behaviors considered for early disease detection.
Subjective Cognitive Decline (SCD) may be an early indicator of risk for Alzheimer's disease (AD). Findings regarding sex differences in SCD are inconsistent. Studying sex differences in SCD within ...cognitively unimpaired individuals with autosomal-dominant AD (ADAD), who will develop dementia, may inform sex-related SCD variations in preclinical AD. We examined sex differences in SCD within cognitively unimpaired mutation carriers from the world's largest ADAD kindred and sex differences in the relationship between SCD and memory performance.
We included 310 cognitively unimpaired Presenilin-1 (PSEN-1) E280A mutation carriers (51% females) and 1998 noncarrier family members (56% females) in the study. Subjects and their study partners completed SCD questionnaires and the CERAD word list delayed recall test. ANCOVAs were conducted to examine group differences in SCD, sex, and memory performance. In carriers, partial correlations were used to examine associations between SCD and memory performance covarying for education.
Females in both groups had greater self-reported and study partner-reported SCD than males (all
< 0.001). In female mutation carriers, greater self-reported (
= 0.02) and study partner-reported SCD (
< 0.001) were associated with worse verbal memory. In male mutation carriers, greater self-reported (
= 0.03), but not study partner-reported SCD (
= 0.11) was associated with worse verbal memory.
Study partner-reported SCD may be a stronger indicator of memory decline in females
males in individuals at risk for developing dementia. Future studies with independent samples and preclinical trials should consider sex differences when recruiting based on SCD criteria.
PDF
