The Stages of Objective Memory Impairment (SOMI) system, based on the Free and Cued Selective Reminding Test (FCSRT), is a potential marker of subtle cognitive impairment in cognitively normal persons defined by a Clinical Dementia Rating (CDR) = 0. We investigated SOMI’s ability to predict incident cognitive impairment (CDR >0) in combination with demographic features and neuroimaging biomarkers.

Cognitively unimpaired participants (CDR = 0) from the Harvard Aging Brain Study had baseline FCSRT scores, MRI, FDG-PET, and PiB-PET as well as follow-up CDRs for 5 years. Cox proportional hazards models with correction for multiple testing assessed the predictive validity of SOMI and neuroimaging biomarkers for progression (CDR >0). Comprehensive sensitivity analyses examined alternative outcomes and stricter screening criteria.

Participants (N = 231) were 73.7 years (SD = 6.0), 60.2% were female, 29.0% were APOE4 positive, and 54 (23.4%) progressed to CDR >0. At baseline, 67% were SOMI-0, 22% were SOMI-1, 4% were SOMI-2, and 7% were SOMI-3/4. After multiple testing correction, hazard ratios (HRs) using SOMI-0 as reference were: SOMI-1 = 2.06 (CI: 1.09 – 3.88), SOMI-2 = 2.85 (CI: 1.08 – 7.54), and SOMI-3/4 = 3.73 (CI: 1.58 – 8.79, p = 0.016). SOMI-3/4 remained significant across most biomarker models. Entorhinal thickness emerged as the most robust biomarker predictor (HR = 0.57 – 0.65, p ≤ 0.015). Sensitivity analyses confirmed robustness across alternative outcomes and stricter screening criteria.

SOMI stages predict progression to incident cognitive impairment with SOMI-3/4 maintaining significance after rigorous multiple testing correction. Entorhinal thickness provides the strongest biomarker enhancement to prediction models. SOMI demonstrates substantial incremental predictive value beyond standard demographic and biomarker predictors.

This study examined three neurocognitive patterns or “clinical pearls” historically viewed as evidence for executive dysfunction in Parkinson disease (PD): 1) letter < category fluency; 2) word list < story delayed recall; 3) word list delayed recall < recognition. The association between intraindividual magnitudes of each neuropsychological pattern and individual performance on traditional executive function tests was examined.

A clinical sample of 772 individuals with PD underwent neuropsychological testing including tests of verbal fluency, word list/story recall, recognition memory, and executive function. Raw scores were demographically normed (Heaton) and converted to z-scores for group-level analyses.

Letter fluency performance was worse than category fluency (d = −0.12), with 28% of participants showing a discrepancy of ≥ −1.0 SD. Delayed recall of a list was markedly poorer than story recall (d = −0.86), with 52% of the sample exhibiting ≥ −1.0 SD deficits. Lastly, delayed free recall was worse than recognition memory (d = −0.25), with 24% showing a discrepancy of ≥ −1.0 SD. These patterns did not consistently correlate with executive function scores. The word list < story recall pattern was more common in earlier than later PD stages and durations.

Among the three pearls, the most pronounced was stronger memory performance on story recall than word lists, observed in more than half the sample. Only ¼ the participants exhibited all three neurocognitive patterns simultaneously. The variability in patterns across individuals highlights the heterogeneity of cognitive impairment in PD and suggests that intra-individual comparisons may offer a more nuanced insight into cognitive functioning.

Despite recent attention to the increased risk of cognitive impairment in older adults with essential tremor (ET), there are only limited data on the trajectories of cognitive change in ET or the demographic and motor predictors of such change.

This study included 148 cognitively normal individuals with ET (mean age = 76.7 ± 9.7 years) at baseline and had at least one follow-up evaluation (mean years of observation = 5.2 ± 1.6). Generalized Estimating Equations examined rates of change in six composite cognitive outcomes as a function of time, as well as demographic (age, sex, and education) and motor predictors (tremor severity, age of tremor onset, presence of rest tremor, cranial tremor, intention tremor, tandem gait) of rates of change. Demographics, medication use, and mood symptoms at baseline were covariates for all models.

Participants evidenced a decline in global cognition, executive function, and attention (prange = <0.001–0.044) over time. Older age predicted faster decline in all cognitive outcomes except attention (prange =<0.001–0.025). Tremor severity predicted faster decline in executive function (p = 0.011). Rest tremor predicted faster decline in executive function and attention (p = 0.033, 0.017). Tandem gait missteps predicted faster decline in memory and visuospatial ability (p = 0.026, 0.028).

Results point to a dissociation in the predictive value of different motor features for specific aspects of cognitive decline. These results shed light on the earliest manifestations of cognitive impairment in older adults with ET and implicate different pathways by which heterogeneous cognitive changes emerge.

We compare the Emory 10-item, 4-choice Rey Complex Figure (CF) Recognition task with the Meyers and Lange (M&L) 24-item yes/no CF Recognition task in a large cohort of healthy research participants and in patients with heterogeneous movement disorder diagnoses. While both tasks assess CF recognition, they differ in key aspects including the saliency of target and distractor responses, self-selection versus forced-choice formats, and the length of the item sets.

There were 1056 participants from the Emory Healthy Brain Study (EHBS; average MoCA = 26.8, SD = 2.4) and 223 movement disorder patients undergoing neuropsychological evaluation (average MoCA = 24.3, SD = 4.0).

Both recognition tasks differentiated between healthy and clinical groups; however, the Emory task demonstrated a larger effect size (Cohen’s d = 1.02) compared to the M&L task (Cohen’s d = 0.79). d-prime scoring of M&L recognition showed comparable group discrimination (Cohen’s d = 0.81). Unidimensional two-parameter logistic item response theory analysis revealed that many M&L items had low discrimination values and extreme difficulty parameters, which contributed to the task’s reduced sensitivity, particularly at lower cognitive proficiency levels relevant to clinical diagnosis. Dimensionality analyses indicated the influence of response sets as a potential contributor to poor item performance.

Emory CF Recognition task demonstrates superior psychometric properties and greater sensitivity to cognitive impairment compared to the M&L task. Its ability to more precisely measure lower levels of cognitive functioning, along with its brevity, suggests it may be more effective for diagnostic use, especially in clinical populations with cognitive decline.

The cognitive trajectory of aging individuals with childhood-onset epilepsy is poorly understood. Our aim was to examine cognitive change over a 7-year period in aging individuals with epilepsy, originally recruited for prospective follow up in the early 1960’s.

36 participants with childhood-onset epilepsy from a prospective population-based cohort and 39 controls participated in the 50-year and 57-year follow-up data collections. Eight participants had active epilepsy, 28 were in remission. Eleven neuropsychological tests were used to measure language/semantic function, episodic memory and learning, executive function, visuomotor function, and working memory. Regression-based standardized change scores were used to control for sources of error in test-retest assessments.

Participants with epilepsy lacked a test-retest effect in language functions. A significant decline was found in participants with active epilepsy in episodic memory functions overall, and in those with remitted epilepsy in learning, immediate recall and set-shifting. The risk of clinically significant general cognitive decline was higher in participants with active epilepsy (OR 61.25, 95% CI 5.92–633.81, p = .0006). Among those with remitted epilepsy the risk was lower and non-significant (OR 2.19, 95% CI 0.58–8.23, p = .24).

Our results demonstrate poorer cognitive trajectories in participants with childhood-onset epilepsy compared to controls, particularly in those with active epilepsy. The risk of general cognitive decline was lower in participants with remitted epilepsy, but a decline in episodic memory functions was observed. Our findings likely reflect faster brain aging in childhood-onset epilepsy, even in individuals with early remission.

The impact of chronic pain and opioid use on cognitive decline and mild cognitive impairment (MCI) is unclear. We investigated these associations in early older adulthood, considering different definitions of chronic pain.

Men in the Vietnam Era Twin Study of Aging (VETSA; n = 1,042) underwent cognitive testing and medical history interviews at average ages 56, 62, and 68. Chronic pain was defined using pain intensity and interference ratings from the SF-36 over 2 or 3 waves (categorized as mild versus moderate-to-severe). Opioid use was determined by self-reported medication use. Amnestic and non-amnestic MCI were assessed using the Jak-Bondi approach. Mixed models and Cox proportional hazards models were used to assess associations of pain and opioid use with cognitive decline and risk for MCI.

Moderate-to-severe, but not mild, chronic pain intensity (β = −.10) and interference (β = −.23) were associated with greater declines in executive function. Moderate-to-severe chronic pain intensity (HR = 1.75) and interference (HR = 3.31) were associated with a higher risk of non-amnestic MCI. Opioid use was associated with a faster decline in verbal fluency (β = −.18) and a higher risk of amnestic MCI (HR = 1.99). There were no significant interactions between chronic pain and opioid use on cognitive decline or MCI risk (all p-values > .05).

Moderate-to-severe chronic pain intensity and interference related to executive function decline and greater risk of non-amnestic MCI; while opioid use related to verbal fluency decline and greater risk of amnestic MCI. Lowering chronic pain severity while reducing opioid exposure may help clinicians mitigate later cognitive decline and dementia risk.

CD33 has been implicated in the pathogenesis of Alzheimer’s disease primarily through its role in inhibiting the clearance of beta-amyloid (Aβ). However, genetic studies yield mixed results and it is unclear whether the impact of CD33 is specific to Alzheimer’s disease or related to broader neurodegenerative processes. Interestingly, CD33 has also been shown to interact with the hepatitis B (HBV) and C viruses (HCV).

This study aims to investigate the effects of CD33 single-nucleotide polymorphisms (SNPs) on cognitive functions across diverse populations, including healthy controls, individuals with chronic HBV or HCV and those diagnosed with Parkinson’s disease.

We genotyped CD33 SNPs in 563 participants using the Affymetrix platform. Participants’ cognitive functions were cross-sectionally assessed using a neuropsychological test battery spanning six domains.

Our analysis revealed that CD33 SNP variations had no significant cognitive impact on healthy individuals or Parkinson’s disease patients. However, chronic HBV and HCV patients exhibited significant cognitive differences, particularly in memory, related to CD33 SNP genotypes. Moderation analysis indicated a heightened influence of CD33 SNPs on cognitive functions in chronic HBV and HCV individuals. Our data also suggest that inflammation severity may modulate the cognitive effects in hepatitis patients with specific CD33 SNPs.

This study highlights the importance of CD33 SNPs in cognitive outcomes, emphasising their role in the context of chronic viral hepatitis. It contributes to understanding the cognitive profiles influenced by CD33 SNPs and posits CD33’s potential contribution to neurodegenerative disease progression, potentially intensified by HBV/HCV-induced inflammation.