bluuebunny/crossref_metadata_2025 huggingface dataset:
COVID‐19 and cognitive impairment in the elderly: A literature review
Authors: Veerapaneni Seshagiri , Raji Mukaila
Published: December 2021

Background

COVID‐19 was declared a pandemic by the World Health Organization on the 11th of March 2020, and it represents an unprecedented immediate and persistent threat to our health care systems. Emerging data reveals neurological symptoms and subclinical cognitive dysfunction and the development of dementia or worsening of it coming to light in the elderly.

Method

An exhaustive search of scientific publications, which included original articles and reports was conducted using the online search databases like Pub Med, with search terms used being neurologic manifestations of COVID‐19, neurological complications of novel coronavirus 2019, with relevant articles analyzed for a possible neurological syndrome related to COVID‐19. Based on specific selection criteria the relationship between COVID‐19 and the nervous system was established and a brief narrative literature review was done.

Result

There has been convincing evidence that SARS‐CoV‐2, the etiologic agent of COVID‐19 can affect the nervous system with consequent damage and neurologic alterations with causation of cognitive decline and worsening of dementia in the elderly survivors.

Conclusion

Based on evidence gathered from scientific literature, this review raises a possibility of nervous system involvement in COVID‐19 with progression to dementia or worsening of existing Dementia especially in the elderly patients. Longitudinal neurological assessments of patients after recovery will be crucial in understanding the natural History of COVID‐19 in the CNS and monitoring for potential neurologic sequalae and long‐term effects on causation and worsening of dementia. The literature review also states the need to start investigating the mechanistic link between Alzheimer's disease and COVID‐19 for further follow up.
Clock‐drawing center estimation varies with age and Alzheimer's disease
Authors: Chapin Benjamin Albert , Formanski Erin , Amini Shawna , Davoudi Anis , Emrani Sheina , Matusz Emily , Wasserman Victor , Price Catherine C. , Libon David J , Heilman Kenneth
Published: December 2021

Background

Healthy, young adults deviate leftward when bisecting horizontal lines and upward when bisecting vertical lines, a phenomenon termed “pseudoneglect”. With aging, there is a reduction in this leftward bias. Alzheimer’s disease (AD) can be associated with neglect. Our research assessed directional bias in healthy controls, patients with amnestic mild cognitive impairment (aMCI), and AD with the digital Clock Drawing Test (dCDT) command test condition.

Method

The sample included 68 cognitively normal older adults (M= 72.08, SD= 5.1), 16 younger healthy adults (M= 31.34, SD= 5.83), 13 patients with aMCI (M= 72.56, SD= 6.00), and 24 patients with AD (M= 80.34, SD= 5.97). dCDT protocols were selected for correct number placement within 30 degrees of ideal and hands directed toward the correct digits. The estimated center of the clock face was determined by the point where clock hands converged. Horizontal and vertical deviations of this estimated center from the actual center in each group were normalized as percentages of the clock face diameter.

Result

Horizontal deviation: Younger adults deviated leftward(M= 3.55%, SD = 2.82%) and differed from older controls (p= 0.003) who were near center with leftward deviation (0.31%, SD 2.58%). AD patients deviated leftward (M= 3.77%, SD = 4.58%) relative to older controls (p= 0.008). aMCI patients also deviated leftward (M= 2.18%, SD=2.36%) and differed from older controls (p= 0.047).

Vertical deviation: Every group deviated upward relative to center (M= 1.82%, SD= 5.09%; p< 0.001).

Conclusion

On average, clock center estimation deviates upward similarly across age and AD related neurodegeneration. Leftward “pseudoneglect” was present in younger clocks and decreased with age. AD and aMCI were associated with greater leftward deviation compared to healthy older adults. Leftward deviation on the dCDT may be a useful marker predicting cognitive impairment in otherwise “normal” clocks.
PET imaging biomarkers: What is the outlook for their role in research, trials, and practice?
Authors: Landau Susan M.
Published: December 2021

Background

Positron emission tomography (PET) imaging is an increasingly widespread tool for the identification of Alzheimer’s disease (AD) pathophysiology. PET biomarkers of Aβ and tau pathology, together with fluid biomarkers and ex vivo pathology validation, have enabled detection of early regional changes and identification of individuals who are unimpaired but on the AD pathway. This presentation will address the changing and complementary role of PET biomarkers in relation to fluid biomarkers in AD clinical trials, research, and practice.

Method

Recent PET imaging work from natural history studies targeting Aβ and tau pathology will be reviewed, with an emphasis on early detection of dynamic regional changes in unimpaired individuals in relation to fluid biomarkers and cognition. Relationships between Aβ and tau PET measurements to other biomarkers and pathology will be discussed, as well as the status of emerging PET markers of inflammation and synaptic integrity.

Result

A key unique feature of PET imaging is that it offers a regionally‐specific view of fibrillar Aβ and paired helical filament (PHF) tau pathology in vivo. Initial Aβ and tau changes are detectable over a decade before the onset of clinically‐relevant cognitive symptoms. There is a predictable time course of Aβ and tau change over the course of disease, and regional tau accumulation predicts local neurodegenerative changes. In symptomatic individuals, inferolateral temporal tau accumulation is sensitive to AD and useful for differential diagnosis. However, tau accumulation is also highly variable even among symptomatic Aβ+ individuals, likely due to co‐pathology and the influence of poorly understood factors such as age, sex, genetics, and cardiovascular risk. There are a number of technical and cost considerations for successful implementation of PET relative to other biomarkers in research, trials, and clinical practice.

Conclusion

Early, regionally‐specific Aβ and tau PET measurements predict downstream neurodegeneration and cognitive decline. Such early changes represent an opportunity for therapeutic intervention, but identification of individuals who are unimpaired but at risk remains challenging. Additional longitudinal research and development of PET biomarkers for other disease targets will address open questions about how AD develops.
Determinants of polypharmacy in patients with behavioral and psychological symptoms of dementia
Authors: Zarei Shadi , Choudhury Samira , Burhan Amer M. , Chu Li , Colman Sarah , Derkach Peter , Elmi Sarah , Hussain Maria , Ismail Zahinoor , Zarei Shadi , Nair Vasavan , Rej Soham , Rostas Aviva , Rajji Tarek K. , Streiner David , Kumar Sanjeev ,   StaN Study Group
Published: December 2021

Background

Polypharmacy is common in patients with dementia and is associated with several adverse effects. Factors associated with polypharmacy in patients with behavioral and psychological symptoms of dementia (BPSD) are unclear. This study examined the factors associated with general and psychotropic polypharmacy in patients with BPSD.

Method

Baseline data was obtained from the Standardizing Care for Neuropsychiatric Symptoms and Quality of Life in Dementia (StaN) study, a multisite trial currently underway in Canada at long‐term care and inpatient sites. The Cohen‐Mansfield Agitation Inventory (CMAI) was used to assess agitation and aggression and Cumulative Illness Rating Scale for Geriatrics (CIRS‐G) was used to assess medical burden. General polypharmacy was defined as concomitant use of five or more scheduled medications of any kind, and psychotropic polypharmacy was defined as concomitant use of two or more scheduled psychotropic medications. Correlation, and linear and logistic regressions were performed to investigate the associations of agitation/aggression and polypharmacy.

Result

120 participants were enrolled [50.4% female; mean (SD) age= 80.25 (9.75) years]. 80.2% of participants had general polypharmacy and 56.2% had psychotropic polypharmacy. Total number of medications was positively correlated with CIRS_G (Spearman's r = 0.28, p = 0.002). In linear regression models, CMAI‐frequency (R2 = 0.137, p = 0.003, B = 0.269, p = 0.003) and CMAI‐disruptiveness (R2 = 0.136, p = 0.003, B = 0.268, p = 0.004) were significant predictors, whereas age, current psychiatric diagnosis and setting (inpatient versus long‐term) did not predict the number of psychotropics. Similarly in logistic regression models, CMAI‐frequency (R2 = 0.142, p = 0.002, Wald = 6.93, p = 0.008) and CMAI‐disruptiveness (R2 = 0.141, p = 0.002, Wald = 6.86, p = 0.009) were significant predictors, whereas age, current psychiatric diagnosis and setting did not predict psychotropic polypharmacy.

Conclusion

As expected, medical burden was positively correlated with general medication use. On the other hand, BPSD (agitation and aggression) were associated with total number of psychotropic medications, rather than psychiatric morbidity, age or setting. Improving the management of agitation/aggression might be an important factor in addressing polypharmacy in patients with BPSD.
Pattern separation and pattern completion for human face identity recognition in prodromal Alzheimer’s disease
Authors: Quenon Lisa , Rossion Bruno , Woodard John L. , Hanseeuw Bernard J , Dricot Laurence , Lhommel Renaud , Ivanoiu Adrian
Published: December 2021

Background

The integrity of face identity recognition (FIR) in prodromal Alzheimer’s disease (prAD) is inconsistent in the literature, and the cognitive processes underpinning a potential impairment remain elusive. The concepts of pattern separation (PS) and pattern completion (PC) offer an interesting insight in this respect, since efficient FIR implies that facial identities are stored in at least partly distinct representations (corresponding to a PS process) and to fill‐in the currently perceived facial pattern based on these mnemonic representations (corresponding to the PC process). The goal of our study was therefore to investigate FIR in prAD patients with a PC and PS paradigm. In addition, we aimed to verify that prAD patients were able to individuate faces in a task that does not involve any long‐term memory component.

Method

Thirty‐two healthy older participants and 17 prAD patients were familiarized with 40 facial identities, through a picture‐matching task (Fig. 1.A). Participants then performed a forced‐choice recognition task aiming at assessing and strengthening the memory encoding of these 40 faces (Fig. 1.B). They then underwent separate yes/no recognition tasks involving parametrically controlled blurred or morphed faces (Fig. 2), designed to solicit PC and PS processes respectively (Fig. 1.C‐D). Finally, in two separate discrimination tasks (Fig. 1.E‐F), participants were instructed to determine whether two simultaneously displayed faces were identical or not. These discrimination tasks included the blurred and morphed faces displayed in the PC and PS recognition tasks respectively.

Results

prAD patients showed significantly lower performance than controls in both the PC and PS recognition tasks (Fig. 3). However, this group difference was not significant when the recognition accuracy index for the non‐manipulated faces (not blurred nor morphed) displayed in these tasks was included as a covariate. In addition, group differences were unexpectedly found for the familiarization and discrimination tasks.

Conclusion

Our study failed to highlight specific PC or PS deficits in prAD patients. However, it showed that prAD patients performed poorly on tasks that required comparing and matching simultaneously presented facial patterns, in the absence of any long‐term memory component. Future research should investigate whether this impairment could represent an early cognitive marker of AD that could be easily assessed in clinical practice.
Reduction of risk of development of Alzheimer’s disease and related dementias in patients with type 2 diabetes by drugs to treat hyperglycemia
Authors: Rodgers Kathleen E , Torrandell‐Haro Georgina , Branigan Gregory L , Brinton Roberta Diaz
Published: December 2021

Background

Alzheimer’s Disease and Related Dementias (ADRD) are progressive neurodegenerative disorders that manifest in reduced cognition, executive function and memory impairments. Type 2 Diabetes (T2D) is suggested to be a risk factor for the development of ADRD. In this study, we evaluated the effects of anti‐hyperglycemic medications (HM) to treat hyperglycemia in T2D patients on the incidence of newly diagnosed ADRD.

Method

Using a retrospective analysis of healthcare claims dataset (Mariner 30), patients receiving HM for T2D treatment were identified and survival analysis, stratified by individual therapeutics, was used to determine the association between HM exposure and diagnosis of ADRD. A propensity score approach was used to minimize measured and unmeasured selection bias.

Result

In this cohort study of propensity score matched T2D patients over the age of 45, HM exposure was associated with decrease in diagnosis of ADRD, most specifically AD (RR, 0.61; 95% CI, 0.59‐0.62; P <0.001), Vascular Dementia (RR, 0.72; 95% CI, 0.69‐0.74; P < 0.001) and Dementia (RR, 0.65; 95% CI, 0.64‐0.66; P < 0.001). Patients that did not use HM were more likely to develop an ADRD. The protection by the use of HM was more pronounced after propensity score matching comorbidities significantly correlated with the assignment to HM treatment. Metformin was the most protective and insulin was the least protective compared to patients not taking any HM. The differences between these therapies was not due to age, gender or Charleston Comorbidity Index.

Conclusion

After controlling for age, gender and comorbidities, the use of HM in patients with T2D protected against the development of ADRD.
Ranking qualitative and timing‐based verbal fluency scores as predictors of incident cognitive impairment
Authors: Bushnell Justin , Svaldi Diana , Ayers Matthew , Gao Sujuan , Unverzagt Fredrick , Gaizo John Del , Wadley Virginia G , Kennedy Richard E , Goñi Joaquín , Clark David G.
Published: December 2021

Background

Verbal fluency tasks are a valuable tool for neuropsychological assessment of cognitive impairment. In recent decades, researchers have proposed qualitative scores, such as clustering and switching, to index cognitive processes underlying fluency. However, the best approach to computing these scores is not clear, and no study addresses the handling of erroneous utterances.

Method

We transcribed animals and letter F fluency recordings on 703 cases of ICI and matched controls from the REGARDS study, amending each transcription with word timings. We then calculated clustering and switching scores with three methods described in the literature and new scores indexing speed of switch and edge transitions. After fitting a base model with only counts of valid words, perseverations, and intrusions, we fit a series of logistic regression models adding either clustering and switching scores or switch and edge speed scores, ranking the models with Watanabe‐Akaike Information Criterion.

Results

For animal fluency, we found that a model with switch‐edge speeds dominated the other models. Clustering and switching, when defined by the slope difference algorithm, offered a slim improvement over the base model. For letter fluency, none of the novel scores we computed yielded an improvement over the base model. A model with animal and letter fluency variables offered further improvement.

Conclusion

Switch‐edge speed scores improve on a base model predicting ICI from animal fluency. Animals and letter F fluency provide complementary prognostic information.
Associations between different FDG PET indices and clinical ratings in cognitively unimpaired older adults
Authors: Protas Hillary D. , Chen Kewei , Chen Yinghua , Luo Ji , Raichle Marcus E. , Morris John C. , Benzinger Tammie L.S. , Goyal Manu S. , Vlassenko Andrei G. , Reiman Eric M. , Su Yi
Published: December 2021

Background

FDG PET measurements of cerebral glucose hypometabolism in brain regions that are preferentially affected by Alzheimer’s disease (AD) are known to be associated with clinical decline. However, commonly used FDG PET indices such as the standard uptake value ratio (SUVR) lack the sensitivity to detect early metabolic changes associated with cognitive decline. In this study we examine whether the full quantitative FDG net uptake rate (Ki) can track metabolic change in cognitive unimpaired elderly (CU) and compare that with indices that do not require full dynamic acquisition including the AD‐related hypometabolic convergence index (HCI), the AD‐related statistical region of interest (sROI), and regional SUVRs from known AD affected brain regions, e.g. precuneus (SUVRpre), posterior cingulate (SUVRpc) and hippocampus(SUVRhipp).

Method

Dynamic FDG PET images were acquired between 0 and 60 min after intravenous radiotracer administration in 75 subjects (all with CDR=0, age 67±7 years) from Washington University cohort. Full quantification of FDG PET was achieved using an image‐derived arterial input function to estimate hippocampal Ki. A Patlak model with reference region was used to estimate the hippocampal relative uptake rate Ri. HCI, sROI, SUVRpre, SUVRpc, SUVRhipp were also estimated using the last 30 minutes of data from each dynamic scan. Using Pearson correlation (r), we examined MMSE association with Ki, Ri, SUVRpre, SUVRpc, SUVRhipp, HCI and sROI each separately. Using statistical Steiger test, we compared the difference of these correlation strengths.

Result

Lower hippocampal Ki and AD‐related sROI FDG measurements were significantly correlated with lower MMSE in CU older adults (r=0.31, p=0.007, r=0.27, p=0.019), but not Ri, HCI, SUVRpre ,SUVRpc, and SUVRhipp (r=0.09,‐0.06,0.13,0.12,0.03, p>0.28). MMSE correlations with hippocampal Ki and AD‐related sROI measurements were not significantly different (p=0.74, Steiger test). Among the FDG indices that did not require full dynamic scan, sROI also had the strongest correlation with Ki (r=0.39, p<0.001).

Conclusion

Among the tested FDG PET indicators of AD, lower Hippocampal Ki and AD‐related sROI measurements were associated with lower clinical ratings in CU older adults. Additional studies are needed to clarify the extent to which they predict subsequent cognitive decline.
White matter neuroinflammation correlates cognition in preclinical Alzheimer disease
Authors: Wang Qing , Schindler Suzanne E. , Chen Gengsheng , McKay Nicole S. , Liu Jingxia , Flores Shaney E. , Wang Sicheng , Hassenstab Jason , Morris John C. , Wang Yong , Benzinger Tammie L.S.
Published: December 2021

Background

Although neuroinflammation plays a critical role in the progression of Alzheimer disease (AD), the exact mechanism underlying neuroinflammation remains largely unclear. Neuro‐inflammation imaging (NII), a diffusion‐based MRI method for neuroinflammation, has been used to quantify white matter (WM) neuroinflammation in the sporadic AD. This study aims to evaluate WM neuroinflammation in reference to the A/T/N framework of AD and assess its associations with cognition.

Method

266 participants enrolled in ongoing studies at the Knight ADRC at Washington University underwent NII measures, CSF biomarker measures, and a test battery of cognitive tasks. The CSF levels of Aβ42/Aβ40, ptau181, and total‐tau were measured with the automated Lumipulse platform and used to classify the participants into the following groups – A‐T‐N‐ (n=145), A+T‐N‐ (n=71), and A+T+N+(n=50) (Table 1). The preclinical Alzheimer Cognitive Composite (PACC) and Global Composite scores for each individual were derived from a subset of the Knight ADRC cognitive battery to assess cognitive performance. NII was acquired with a multi‐b value scheme (bmax =1400s/mm2 and 25 directions). The whole WM neuroinflammation (unit, mm2/ms) was quantified using the Tract Based Spatial Statistics (http://www.fmrib.ox.ac.uk/fsl) based WM skeleton. All statistical tests were conducted in R (R Core Team, 2020). Continuous and categorical variables in characteristics across all the three groups were compared using the Kruskal‐Wallis test and the Chi‐square tests where appropriate. The correlation between the NII WM neuroinflammation and cognition was determined by Spearman correlation. Analyses were adjusted for covariates, including age, sex, education, and APOE ε4 carrier status.

Result

NII WM neuroinflammation was significantly correlated with the PACC (Figure 1A) and Global Composite score (Figure 1B) in all participants. Significant correlations between NII WM neuroinflammation and cognition composite scores were found in the A‐T‐N‐ and the A+T+N+ groups (Figure 1).

Conclusion

Our findings suggest that NII WM neuroinflammation is associated with cognitive performance both in individuals with no evidence of brain amyloidosis and in individuals with biomarkers consistent with Alzheimer disease. Given that this measure is acquired without using a contrast agent or radioactive tracer, NII holds great promise as an accessible measure for quantifying neuroinflammation in AD pathogenesis.
Metabolic syndrome in relation to cognitive function and white matter integrity in midlife: The CARDIA study
Authors: Dintica Christina S , Allen Norrina , Sidney Stephen , Yaffe Kristine
Published: December 2021

Background

Metabolic syndrome (MetS) has been associated with poorer cognition in old age, however this association has yet to be defined in midlife. We aimed to investigate the relationship of early adulthood to midlife MetS in relation to cognition and white matter integrity in midlife.

Methods

Within the prospective study of Coronary Artery Risk Development in Young Adults, 2882 participants were identified with follow‐up of 30 years (age 18–30 years at baseline). MetS was defined using National Cholesterol Education Program guidelines and assessed across 9 follow‐ups over 25 years. Cognitive function was assessed at Year 30 using the Rey Auditory Verbal Learning Test (verbal memory), Digit Symbol Substitution Test (processing speed), Stroop test (executive function) and Verbal Fluency. Using logistic regression, we examined the association of MetS at Year 25, and persistent MetS (at least two assessments over the follow‐up) with poor mid‐life cognition, defined as ≥1 standard deviation below the mean in each domain. In a sub‐sample (n=453), brain MRI measures of total and region‐specific white matter integrity (fractional anisotropy [FA] and mean diffusivity [MD]) were assessed at Year 30 (mean age of 55±3.5 years) and converted to standardized z‐scores.

Results

MetS at Year 25 (n=534, 18.54%) was associated with poor cognitive function five years later in verbal memory (OR: 1.32, 95% CI: 1.04; 1.67) and processing speed (OR: 1.59, 95% CI: 1.23; 2.05), adjusting for age, sex, education, race, income, and smoking. Similarly, participants with persistent MetS over 25 years had lower cognitive performance in verbal memory (OR: 1.38, 95% CI: 1.10;1.73) and processing speed (OR: 1.72, 95% CI: 1.34; 2.22). In the MRI sub‐sample, MetS at Year 25 (n=60, 13.3%) was associated with lower total FA (β: ‐0.31, 95% CI: ‐0.57; ‐0.05). Persistent and non‐persistent MetS was associated with lower frontal FA (β: ‐0.36, 95% CI: ‐0.62; ‐0.09, β: ‐0.21, 95% CI: ‐0.62; ‐0.08, respectively) and higher total MD (β: 0.30, 95% CI: 0.03; 0.56, β: 0.26, 95% CI: 0.01; 0.51, respectively).

Conclusion

MetS from early adulthood to midlife may be a risk factor for poor cognitive function in midlife and is associated with microstructural white matter differences.
Successful cognitive aging definitions and associated demographic, biomarker profiles and lifestyles in the 80+ MCSA population
Authors: Arenaza‐Urquijo Eider M , Castillo Anna , Przybelski Scott A. , Lesnick Timothy G. , Pillai Sheela Kumari Raghavan , Mielke Michelle M. , Machulda Mary M. , Knopman David S. , Radford Jonathan Graff , Jack Clifford R. , Petersen Ronald C. , Vemuri Prashanthi
Published: December 2021

Background

There have been no standard definitions of successful cognitive aging (SA). Our goal was to apply different SA definitions to the 80+ population in the Mayo Clinic Study of Aging (MCSA) on the basis of (i) cross‐sectional vs longitudinal cognition (“Exceptionality” vs “Maintenance”) and (ii) memory vs global cognitive scores and explore the participant characteristics for each SA definition on the basis of baseline imaging markers and mid/late‐life health.

Method

We included 2157 participants from the MCSA, all ≥80 years at baseline and classified them into two SA definitions using memory z‐scores or global z‐scores: “Exceptionality” when high cognitive performance was observed (z‐scores ≥ 1 SD), “Maintenance” when cognitive function was preserved over time (Slope ≥ ‐0.1/year using mixed‐effect models). Our imaging markers were: PET‐based amyloid positivity (A+), MRI‐based neurodegeneration positivity (N+), WMH, FDG‐PET SUVR markers of resilience (anterior cingulate, ACC) and AD‐related areas (posterior cingulate). We also examined APOE4 status and other health characteristics. Group comparison was performed within each definition (e.g. exceptional vs non‐exceptional memory) using ANCOVA and binary logistic regressions with adjustments for age, sex, and education.

Result

A lower number of participants met the “Exceptionality” criteria (10%: memory and 4%: global). A greater number met the “Maintenance” criteria (53%: memory and 32%: global). Less than 7% showed both “Exceptional” cognition and “Maintenance” over time. Participants across SA definitions were in general younger, more often women, with a higher education/occupation and less often APOE4 carriers. All SA groups showed higher ACC metabolism and lower N+ compared to the corresponding non‐SA group. More than 50% of the participants in the “Exceptional” groups were A+ (57%: memory, 50%: global). A+ frequency was significantly lower in the “Maintainers” (<42%). Better mid/late‐life health indicators were observed in the SA groups, including lower cardio‐metabolic conditions, higher mid‐life cognitive activities, lower depressive symptomatology, lower hypersomnolence and better self‐perception of health.

Conclusion

Different SA definitions identified mainly non‐overlapping 80+ groups that showed several common features including higher education/occupation, percent of women, better lifestyles, lower N+ frequency, and higher ACC metabolism. Lower A+ frequency was a key distinct feature of “Maintenance”.
Super‐agers in memory are not necessarily super‐agers in other cognitive domains
Authors: Corrada Maria M. , Melikyan Zarui A. , Dominguez Elena N. , Ho ChuChing , Sajjadi S. Ahmad , Kawas Claudia H.
Published: December 2021

Background

SuperAgers are individuals who, despite their advanced age, retain superior cognitive performance. Although there is no consensus on how to define SuperAgers, identifying such individuals remains an important research question as they may help us identify protective factors against cognitive impairment that may be amenable to intervention strategies. Here we explore whether ‘SuperAgers’ who are the best performers in a test of memory, show equally exceptional performance in other cognitive domains.

Method

Participants are from The 90+ Study, a longitudinal study of aging and dementia in people 90 and older. Out of 1,134 participants in the study, the 349 with normal cognition at baseline were included in these analyses. Cognitive diagnosis was based on clinical examination and mental status exam independent of the tests investigated here. We evaluated performance in tests of verbal memory (9‐item California Verbal Learning Test‐long delay [CVLT]), executive function (Trails B), language (15‐item Boston naming test [BNT]), and attention (Digit Span backward [DSB]). For each test, we determined whether participants were in the top quartile of performance (SuperAgers). We investigated whether SuperAgers according to memory were also SuperAgers in other domains. We also tested whether being a SuperAger was related to age, sex, or education.

Result

47 participants were in the top quartile of CVLT with a perfect score of 9 and were classified as memory‐SuperAgers. Of these 47 participants, 8 (17%) were also in the top quartile for Trails B, 14 (30%) in the top quartile for BNT, and 12 (26%) in the top quartile of DSB (Figure). None of the 349 participants were in the top quartile for all four tests and only 13 participants (4%) were in the top quartile for three tests (Figure). Younger age was associated with being a SuperAger for CVLT, Trails B, & BNT and female sex was associated with being a memory‐SuperAger (CVLT) (Table). Education was not associated with being a SuperAger for any test.

Conclusion

In this oldest‐old cohort, those who perform exceptionally well in a memory test do not perform equally well in other cognitive tests suggesting that the biological and sociodemographic determinants of superior performance will vary by cognitive domain.
Subjective memory complaints are associated with longitudinal declines in connected speech language
Authors: Van Hulle Carol A , Koscik Rebecca L , Johnson Sterling C. , Mueller Kimberly D
Published: December 2021

Background

Subjective memory complaints (SMC) in the absence of impaired performance on objective measures increases risk for dementia among some individuals. Connected Speech Language (CSL) is language produced in a continuous sequence as in conversations. Subtle, yet detectable, changes in CSL have been shown to predict cognitive decline, suggesting that changes in discourse are an early clinical symptom of dementia. Here we examined whether a baseline assessment of SMC was associated prospectively with longitudinal CSL age‐related trajectories.

Method

N=1039 participants who completed SMC and CSL assessment were drawn from the Wisconsin Registry for Alzheimer’s Prevention, a longitudinal study of preclinical AD, in middle‐aged adults. SMC reflects the average rating (1‐7) across the Memory Functioning Questionnaire frequency of forgetting subscale. To ensure SMC did not reflect transient memory problems, participants were grouped into no self‐reported problems, persistent self‐reported problems, or inconsistent self‐reported problems (Figure 1) across time. Participants in the inconsistent group (n = 237) and those with fewer than three SMC assessments (n=54) were excluded from analyses. Participant’s speech was recorded while describing the “Cookie Theft” picture from the Boston Diagnostic Aphasia Examination. CSL outcomes included content information units (CIU density), content units per minute (CIU minutes), types‐tokens ratio, and filled pauses. We tested the moderation of CSL age related trajectories by baseline SMC. Linear mixed models included a random intercept, gender, reading ability, and practice effects as fixed covariates.

Result

Sample characteristics are shown in Table 1 by SMC group. The persistent problem group had fewer years of education and lower WRAT reading scores than the no problems group, but were otherwise comparable. Baseline SMC did not moderate age‐related changes in CIU density, types‐tokens ratio or filled pauses. Baseline SMC moderated changes in CIU Minutes at trend level (Table 2 and Figure 2). Greater memory complaints at baseline were associated with faster age‐related decline in the contents unit/minute compared to those with fewer complaints.

Conclusion

SMC modestly, prospectively related to difficulties expressing ideas. Self‐reported may precede subtle cognitive changes. Future work will examine whether SMC predicts declines in standard cognitive tests of verbal ability.
Study participant self‐installed deployment of a home‐based digital assessment platform for dementia research
Authors: Gothard Sarah , Nunnerley Michael , Rodrigues Nathaniel , Wu Chao‐Yi , Mattek Nora , Hughes Adriana M , Kaye Jeffrey A , Beattie Zachary
Published: December 2021

Background

The Oregon Center for Aging & Technology (ORCATECH) has developed, refined, and deployed to hundreds of diverse older adults a home‐based research platform for providing assessment of cognition and multiple domains of function. The pandemic has brought to the forefront the necessity of this type of remotely conducted research. Even absent a pandemic, there are millions of people who are shut‐out of participating in research because of limitations of mobility, distance, and study partner support. Hence, work is being done to make the ORCATECH platform fully self‐installable by research participants in their homes using Self‐installation Instruction Modules (SIMs) which consist of video tutorials, images, and step‐by‐step instructions.

Method

We developed and sent seven older adults residing in seven separate residences a web‐link to the SIMs. The participants were enrolled in the Aging Well Study which utilizes the ORCATECH platform’s hub computer and electronic pillbox to remotely assess cognition and function. Time to complete installation was captured within the SIMs interface. Labeled and activated technologies were sent to participants’ homes prior to the link being distributed. A survey was sent to participants after the completion of installation for the purpose of gathering feedback about the SIMs experience.

Result

The seven participants include two married and five single person homes (age 73.9(SD=7.1) years, education 17(SD=3) years, 5 women, 5 mild cognitive impairment (MCI)(Clinical Dementia Rating=0.5)). All participants successfully installed their technologies using the SIMs. The SIMS were viewed on four different device types (tablet, smart phone, laptop, desktop). Mean time to install both technologies was 20.0(SD=13.7) minutes for those with MCI; 23.7(SD=10.9) minutes for healthy controls. Participants reported the SIMs was easy to read, hear, and navigate.

Conclusion

Results suggest that it is feasible for older adults of varying ages and cognitive function to install technologies for the purpose of remote data collection without any study personnel being physically present in the home. Further studies are necessary to better understand the impacts of diverse residence and resident characteristics (e.g., home layout, technical proficiency, physical abilities) on a volunteer’s ability to self‐install the technology.
Effects of familiar olfactory stimulation on self‐consciousness
Authors: Arbeláez María Alejandra Castro , Acosta Daysi , Arrollo‐Anlló Eva María
Published: December 2021

Background

Autobiographical memory involves self‐life episodes and generic knowledge that enables the meaning attributed to a lifetime story. The semantic autobiographical memory is related to a general knowledge and the episodic autobiographical memory is associated to the personal experiences at specific time and place related to past experiences among a long period of life (Allen, et al., 2018; Eustache et al., 2013, 2016). Autobiographical events activate an autonomic consciousness related to recovers the past memories, while autobiographical semantic knowledge comprises a noetic familiar awareness and a consciousness of past limited (Markowitsch , & Staniloiu, 2011; Piolino et al., 2003; Tulving, 2002). Progressive loss of self‐consciousness presented in Alzheimer Disease (A.D) is connected to the decline of autobiographical episodic memory. Some studies validate positive effects of olfactory stimulation on autobiographical memory (El Haj et al., 2015; Gachet & El Haj, 2020) but no research has evaluated the influence of familiar olfactory stimulation on A.D related to improve self‐consciousness in Colombia. This study aims to assess if the evoked autobiographical memories from familiar olfactory stimulation has an enforcement or facilitator effect on self‐consciousness.

Method

Fifty people will participate, 25 at the control group and 25 at the experimental group. The control group will have an olfactory stimulation without familiar smells, and the experimental grouo, will have it with familiar smells. There will be three phases: 1) After intervention: Evaluation of autobiographical episodic memory; 2) During intervention: Placebo olfactory stimulation with control group, and olfactory familiar stimulation with experimental group. Then there will be an evaluation of autobiographical episodic memory; 3) Before intervention: Post olfactory stimulation of self‐consciousness.

Results

More autobiographical memories evoked are expected with the positive valiance of familiar olfactory intervention than the placebo olfactory stimulation in people with A.D. We expect that autobiographical episodic involuntary memories evoked will be more elevated than the voluntary ones on subjective content. We also contemplate that the group of patients with familiar olfactory stimulation will improve their level of self‐consciousness and evoke autobiographical episodic memory.

Conclusion

This research will be an important framework for future clinical trials with familiar olfactory intervention in Latin America. Also, for non‐pharmacologic interventions.
Alzheimer's disease clinical onset and age at death in people with Down syndrome: A systematic review and population‐based study
Authors: Iulita M. Florencia , Garzón Diana , Bejanin Alexandre , Tamayo Natalia Valle , Videla Laura , Altuna Miren , Valldeneu Sílvia , Barroeta Isabel , Benejam Bessy , Fernandez Susana , Padilla Concepción , Carmona‐Iragui Maria , Blesa Rafael , Lleó Alberto , Fortea Juan
Published: December 2021

Background

Despite better medical care and social support, life expectancy in people with Down syndrome (DS) is still close to 60 years, about 20 years less than in the general population. Alzheimer’s disease (AD), which has a lifetime risk of >90% in DS, might be the cause. We conducted a systematic review to interrogate the age of onset of symptomatic AD and the age of death in this population.

Methods

Our protocol was registered in the PROSPERO database (CRD42020203967). We performed a systematic search using PubMed, Embase, CINAHL and Web of Science. Only peer‐reviewed, original research studies written in English were considered. No time period restrictions were applied. Studies were eligible if they described research on adults with DS, had good methodological quality, and if they contained numerical results (mean and SD or standard error) of the following outcomes: age at onset or age at diagnosis of symptomatic AD (based on expert clinical judgment), age at death after onset of AD, and/or duration of the disease (time in years from onset or diagnosis to death).

Results

We identified 6983 studies for title and abstract screening after duplicate removal. Of these, 259 articles were considered for full text review and 62 studies met the eligibility criteria (Figure 1). Excluded studies and reasons for exclusion are described in Figure 1. The weighted average for AD onset in DS was 54.1 ± 6.5 years (estimated in 4204 individuals) with a standard error of the mean across studies of 0.328. For age of death and disease duration the weighted averages were 57.7 ± 6.5 (data available from 514 individuals), and 5.4 ± 3.9 years (444 individuals), respectively.

Conclusions

The mean age of AD onset in DS is remarkably consistent across studies, with a variability comparable to that reported in autosomal dominant AD. Given the >90% penetrance, the age of onset reported in the studies and the duration of the disease, life expectancy cannot possibly increase for people with DS if we do not find a cure for AD. This disease should therefore be recognized as the top medical and research priority in this population.
Feasibility of multidisciplinary telehealth evaluations in atypical dementia
Authors: Wong Bonnie , Loyer Emmaleigh , Sullivan Courtney , Krivensky Samantha , Lopez Angela Villareyna , Quimby Megan , Hochberg Daisy , Dev Sheena Isha , Putcha Deepti , Eldaief Mark C , Brandt Katie , Dickerson Brad C.
Published: December 2021

Introduction

While cognitive assessment by videoconference has become possible over the past decade, the COVID‐19 pandemic underscores the critical need for expansion and examination of these methods, their appropriateness for various patient populations, and their benefits and limitations. Validity and reliability studies of tele‐neuropsychological testing have been conducted in MCI or mild AD dementia patients (e.g., MMSE=25+); few studies have assessed the feasibility of neurologic examination by video, and none in atypical dementias, assuming that patients with some types (e.g., language, comportment) or greater severity of cognitive‐behavioral impairment would be unable to participate. Here we report the feasibility of telehealth services for a multi‐disciplinary dementia subspecialty clinic that include cognitive‐behavioral and neurologic assessment with patients with atypical neurodegenerative syndromes.

Methods

104 patient‐carepartner (P‐C) dyads met with providers in the MGH FTD Unit by videoconference (March‐December, 2020) for routine clinical care. P‐Cs completed validated questionnaires assessing cognition‐mood/behavior/function on REDCap prior to video clinical interview and cognitive assessment, including the MoCA and Boston Cognitive Exam (BCE2.0), a newly revised brief cognitive assessment battery adapted for telehealth. P‐Cs met with a neurologist for a basic neurologic examination (including eye‐movement examination), review of assessment results, and discussion of care plan. P‐Cs completed a satisfaction survey.

Results

The 104 P‐Cs included a range of atypical neurodegenerative disorders (bvFTD, PCA, PPA, CBS, PSP, eoAD, Multidomain syndrome) mild‐to‐severe impairment (CDR range: 0‐3). 76% completed the MoCA (25% had CDR=2). 36% also completed the BCEv2. Comparison of remote assessment data to previous in‐person testing is ongoing. Of P‐Cs who completed a satisfaction survey, all reported being “very satisfied” with the appointment, with 93% open to participating in a remote visit again. 87% found the telehealth visit comparable to an in‐person visit. 66% preferred a future combination of remote and in‐person visits.

Conclusions

Multi‐disciplinary telehealth visits appear to be feasible with patients with atypical cognitive‐behavioral syndromes of across the severity spectrum. P‐Cs report a high degree of satisfaction with the telehealth visit and an openness to ongoing telehealth visits. Results have implications for increasing accessibility of multidisciplinary medical services for patients and families living with complex forms of dementia.
Postprandial ketone body levels increase following medium‐chain triglyceride oil consumption
Authors: Hillebrandt Heidi L , Dias Cintia B , Barin Edward S , Chatterjee Pratishtha , Shah Tejal M , Basci Ann M , Kaplan Jason , Sohrabi Hamid R , Martins Ralph N
Published: December 2021

Background

Medium‐chain fatty acids (MCFA) are quickly absorbed and transported to the liver. Where they are preferentially metabolised into energy and ketone bodies, as compared to long‐chain fatty acids. Ketone bodies are then transported to the brain and other tissues for energy supply. This makes MCFA the ideal energy source for patients with conditions in which energy deprivation is observed, such as Alzheimer’s disease (AD). In AD, insulin resistance in the brain causes partial glucose deprivation. However, the brain is still able use ketone bodies for energy. Despite the MCFA potential, to our knowledge, a dose effect study has not been previously done in older adults,

Method

This sequential feeding study involved 20 healthy adults aged 50 to 77 years. Participants consumed 3 daily doses of MCFA oil (40% caprylic acid, 28% capric acid, 32% lauric acid) for 7 weeks, doses were increased in 15 mL/day every week (0mL/day in week 1 increasing to 90mL/day in week 7). At baseline and at the end of each week, participants had their anthropometric measurements taken, donated fasting blood and underwent a 2‐hour postprandial analysis. Participation could be discontinued at any time.

Result

Change in postprandial area under the curve for ketone body levels increased compared to baseline in 45% with 5mL (n=20), 42% with 10mL (n=19), 74% with 15mL (n=19), 73% with 20mL (n=15), 79% with 25mL (n=14), 100% with 30mL (n=11), and 75% with 35mL (n=8). However, there were no significant changes in body mass index (BMI), fasting triglycerides and total, low‐density lipoprotein and high‐density lipoprotein cholesterol,

Conclusion

Supplementation with MCFA oil increased postprandial ketone levels in a dose dependent manner, without a significant impact to blood lipids or BMI. However, further investigation is warranted to correlate this increase in postprandial ketone with its brain uptake and utilisation.
Measuring the association between hippocampal volume and memory abilities vulnerable to Alzheimer’s disease in typically developing periadolescent children: Preliminary findings from the PRANK Study
Authors: Sexton Jennifer N , Phipps Connor J , Behm Lillian , DeCesare Thomas A , Heller Abi M , Maerlender Arthur C. , Phatak Vaishali S , Cramer Justin A. , Blair James , Murman Daniel L , Warren David E
Published: December 2021

Background

Childhood development, including the periadolescent period, is associated with significant changes in brain function, brain structure, and cognition. Memory ability, including memory for arbitrary relations, exemplifies cognitive changes that occur during the periadolescent epoch. In adults, declarative/relational memory requires the hippocampus, as demonstrated by the profound memory impairments accompanying hippocampal pathology frequently caused by Alzheimer’s disease (AD). Vulnerability to AD and related memory impairments in late life could be a function of early‐life brain development. Understanding the developmental relationship between hippocampal volume and declarative/relational memory performance would provide any important baseline for comparison of different trajectories. Our ongoing NIA‐funded research project, the Polygenic Risk of Alzheimer’s Disease in Nebraska Kids (PRANK) study, measures brain structure, brain function, cognitive abilities, and Alzheimer’s polygenic risk score in periadolescent children (age 8‐13). Here, we report preliminary data measuring the association between hippocampal volume and memory abilities in the study’s periadolescent sample.

Method

A sample of periadolescent children from the PRANK study provided data for the current project (N=40). Structural MRI data were collected using protocols adapted from the Human Connectome Project, and hippocampal volume was measured through manual tracing. Cognitive variables included relational memory operationalized as performance on the Picture Sequence Memory Task (PSMT) from the NIH Toolbox (a standard neuropsychological battery). We then tested the correlation between hippocampal volume and performance on the relational memory task in periadolescent children.

Result

We found preliminary evidence consistent with differences in the neuropsychological profile and brain structure, specifically in hippocampal volume and declarative/relational memory performance. Our preliminary observations were consistent with significant correlations between regional hippocampal volume and memory performance on the PSMT.

Conclusion

Findings from this preliminary analysis illustrate differences in cognitive abilities in the periadolescent period, in particular, the association between declarative/relational memory and hippocampal volume. Our ongoing PRANK study measures cognitive abilities, brain structure and function, and Alzheimer’s polygenic risk score in periadolescent children. Future work from this study will investigate whether genetic risk for AD is associated with individual differences in brain structure and outcomes on neuropsychological measures in early life.