This virtual issue consists of studies previously published in the Journal of the International Neuropsychological Society and selected on the basis of their content related to one of the most highly researched concepts in behavioral neurology and neuropsychology over the past decade: mild cognitive impairment (MCI). The reliance on cognitive screening measures, staging-based rating scales, and limited neuropsychological testing in diagnosing MCI across most research studies may miss individuals with subtle cognitive declines or mis-diagnose MCI in those who are otherwise cognitively normal on a broader neuropsychological battery of tests. The assembled articles highlight the perils of relying on these conventional criteria for MCI diagnosis and reveal how the reliability of diagnosis is improved when sound neuropsychological approaches are adopted. When these requirements are met, we illustrate with a second series of articles that neuropsychological measures associate strongly with biomarkers and often reflect pathology beyond or instead of typical AD distributions. The final set of articles reveal that people with MCI demonstrate mild but identifiable functional difficulties, and a challenge for neuropsychology is how to incorporate this information to better define MCI and distinguish it from early dementia. Neuropsychology is uniquely positioned to improve upon the state of the science in MCI research and practice by providing critically important empirical information on the specific cognitive domains affected by the predominant neurodegenerative disorders of late life as well as on the diagnostic decision-making strategies used in studies. When such efforts to more comprehensively assess neuropsychological functions are undertaken, better characterizations of spared and impaired cognitive and functional abilities result and lead to more convincing associations with other biomarkers as well as to prediction of clinical outcomes.

Background

Survival and associated clinical and pathological characteristics in Lewy body disease (LBD)-related dementias are understudied. Available studies focus primarily on white non-Hispanic samples.

Objective

We investigated demographic, clinical, and pathological correlates of survival by race and ethnicity in an autopsy-confirmed cohort of LBD cases.

Methods

Using National Alzheimer's Coordinating Center data, we selected participants who self-identified as Black, Hispanic, or white who had neuropathological assessments showing transitional or diffuse LBD pathology. We used Kruskal-Wallis and Pearson χ2 analyses to investigate group differences in demographic and presenting clinical and pathological characteristics. We used linear regressions to identify predictors of survival with sex, age at symptom onset, education, ethnoracial status, LBD pathology type, and Braak tangle stage included in the model.

Results

Data from 1,441 white, 60 Black, and 54 Hispanic participants were available for analysis. Hispanics were more likely to have transitional LBD pathology and had a longer survival than white and Black participants. After controlling for demographic and pathological variables, length of survival did not differ between Hispanics and Black or white participants. Additional key findings demonstrated discrepancies between clinical diagnoses received at last visit and pathological findings, particularly among Black participants.

Conclusion

LBD survival differences by race and ethnicity can be accounted for by LBD pathology type and co-occurring Alzheimer's disease pathology. The discrepancies between clinical diagnoses and pathological findings raise the concern that dementia with Lewy bodies is underdiagnosed in NACC, especially for Black older adults.

Objective

The objective of this study was to determine which aspects of executive functions are most affected in behavioral variant frontotemporal dementia (bvFTD) and best differentiate this syndrome from Alzheimer disease (AD).

Methods

We compared executive functions in 22 patients diagnosed with bvFTD, 26 with AD, and 31 neurologically healthy controls using a conceptually driven and comprehensive battery of executive function tests, the NIH EXAMINER battery (http://examiner.ucsf.edu).

Results

The bvFTD and the AD patients were similarly impaired compared with controls on tests of working memory, category fluency, and attention, but the patients with bvFTD showed significantly more severe impairments than the patients with AD on tests of letter fluency, antisaccade accuracy, social decision-making, and social behavior. Discriminant function analysis with jackknifed cross-validation classified the bvFTD and AD patient groups with 73% accuracy.

Conclusions

Executive function assessment can support bvFTD diagnosis when measures are carefully selected to emphasize frontally specific functions.

Objective

To determine structural MRI and digital microscopic characteristics of REM sleep behavior disorder in individuals with low-, intermediate-, and high-likelihood dementia with Lewy bodies (DLB) at autopsy.

Methods

Patients with autopsy-confirmed low-, intermediate-, and high-likelihood DLB, according to the probability statement recommended by the third report of the DLB Consortium, and antemortem MRI, were identified (n = 75). The clinical history was assessed for presence (n = 35) and absence (n = 40) of probable REM sleep behavior disorder (pRBD), and patients' antemortem MRIs were compared using voxel-based morphometry. Pathologic burdens of phospho-tau, β-amyloid, and α-synuclein were measured in regions associated with early neuropathologic involvement, the hippocampus and amygdala.

Results

pRBD was present in 21 patients (60%) with high-likelihood, 12 patients (34%) with intermediate-likelihood, and 2 patients (6%) with low-likelihood DLB. Patients with pRBD were younger, more likely to be male (p ≤ 0.001), and had a more frequent neuropathologic diagnosis of diffuse (neocortical) Lewy body disease. In the hippocampus and amygdala, phospho-tau and β-amyloid burden were lower in patients with pRBD compared with those without pRBD (p < 0.01). α-Synuclein burden did not differ in the hippocampus, but trended in the amygdala. Patients without pRBD had greater atrophy of temporoparietal cortices, hippocampus, and amygdala (p < 0.001) than those with pRBD; atrophy of the hippocampus (p = 0.005) and amygdala (p = 0.02) were associated with greater phospho-tau burdens in these regions.

Conclusion

Presence of pRBD is associated with a higher likelihood of DLB and less severe Alzheimer-related pathology in the medial temporal lobes, whereas absence of pRBD is characterized by Alzheimer-like atrophy patterns on MRI and increased phospho-tau burden.