%0 Journal Article %J J Alzheimers Dis %D 2023 %T TDP-43 Pathology in the Setting of Intermediate and High Alzheimer's Disease Neuropathologic Changes: A Preliminary Evaluation Across Ethnoracial Groups. %A Huie, Emily Z %A Escudero, Anthony %A Saito, Naomi %A Harvey, Danielle %A Nguyen, My-Le %A Lucot, Katherine L %A LaGrande, Jayne %A Mungas, Dan %A DeCarli, Charles %A Lamar, Melissa %A Schneider, Julie A %A Kapasi, Alifiya %A Rissman, Robert A %A Teich, Andrew F %A Dugger, Brittany N %X

BACKGROUND: Transactive Response DNA Binding Protein 43 kDa (TDP-43) pathology is frequently found in cases with Alzheimer's disease (AD). TDP-43 pathology is associated with hippocampal atrophy and greater AD severity denoted by cognition and clinical representation. Current TDP-43 pathology studies are predominantly based on non-Hispanic White cohorts.

OBJECTIVE: We sought to evaluate the presence of TDP-43 pathology across ethnoracial groups utilizing the National Alzheimer's Coordinating Center; a database containing data from over 29 institutions across the United States. Cases (N = 1,135: Hispanics/Latinos = 29, African Americans/Black Americans = 51, Asians/Asian Americans = 10, American Indians/Alaskan Natives = 2, non-Hispanic White = 1,043) with intermediate/high AD having data on TDP-43 pathology in the amygdala, hippocampus, entorhinal cortex, and neocortex.

METHODS: TDP-43 pathology frequency in each neuroanatomic region among ethnoracial groups were compared using generalized linear mixed effects models with center as a random effect adjusting for age at death, education, and gender.

RESULTS: Although groups were imbalanced, there was no significant difference across ethnoracial groups based on TDP-43 pathology (p = 0.84). With respect to neuroanatomical regions evaluated, there were no significant differences across ethnoracial groups (p-values > 0.06). There were also no significant differences for age at death and gender ratios across ethnoracial groups based on TDP-43 pathology. Although not statistically significant, TDP-43 pathology was present less often in Hispanic/Latinos (34%) when compared to non-Hispanic Whites (46%).

CONCLUSION: While this is a preliminary evaluation, it highlights the need for diverse cohorts and on TDP-43 pathology research across ethnoracial groups. This is the first study to our knowledge having a focus on the neuroanatomical distribution of TDP-43 deposits in Hispanic/Latino decedents with AD.

%B J Alzheimers Dis %V 91 %P 1291-1301 %8 2023 Feb 14 %G eng %N 4 %R 10.3233/JAD-220558 %0 Journal Article %J J Alzheimers Dis %D 2022 %T Anticholinergic Drug Burden and Neurocognitive Performance in the Study of Latinos-Investigation of Neurocognitive Aging. %A Posis, Alexander Ivan B %A Tarraf, Wassim %A Gonzalez, Kevin A %A Soria-Lopez, Jose A %A Léger, Gabriel C %A Stickel, Ariana M %A Daviglus, Martha L %A Lamar, Melissa %A Zeng, Donglin %A González, Hector M %X

BACKGROUND: Studies of cumulative anticholinergic drug burden on cognitive function and impairment are emerging, yet few for Hispanics/Latinos.

OBJECTIVE: To examine associations between anticholinergic use and neurocognitive performance outcomes among diverse Hispanics/Latinos.

METHODS: This prospective cohort study included diverse Hispanic/Latino participants, enrolled in the Study of Latinos-Investigation of Neurocognitive, from New York, Chicago, Miami, and San Diego (n = 6,249). Survey linear regression examined associations between anticholinergic use (measured during baseline [Visit 1] and average 7-year follow up [Visit 2]) with global cognition, episodic learning, memory, phonemic fluency, processing speed, executive functioning, and average 7-year change.

RESULTS: Anticholinergic use was associated with lower cognitive global cognition (β= -0.21; 95% CI [-0.36; -0.05]), learning (β= -0.27; 95% CI [-0.47; -0.07]), memory (β= -0.22; 95% CI [-0.41; -0.03]), and executive functioning (β= -0.22; 95% CI [-0.40; -0.03]) scores, particularly among those who took anticholinergics at both visits. Anticholinergic use was associated with faster decline in global cognition, learning, and verbal fluency (β: -0.28 [95% CI: -0.55, -0.01]; β: -0.28 [95% CI: -0.55, -0.01]; β: -0.25, [95% CI -0.47, -0.04], respectively). Sex modified associations between anticholinergic use with global cognition, learning, and executive functioning (F3 = 3.59, F3 = 2.84, F3 = 3.88, respectively).

CONCLUSION: Anticholinergic use was associated with lower neurocognitive performance, especially among those who used anticholinergics at both visits, among a study population of diverse Hispanics/Latinos. Findings will support evidence-based decisions regarding anticholinergic prescriptions and efforts to minimize cognitive impact.

%B J Alzheimers Dis %V 86 %P 53-65 %8 2022 Mar 08 %G eng %N 1 %R 10.3233/JAD-215247 %0 Journal Article %J J Alzheimers Dis %D 2020 %T Alzheimer's/Vascular Spectrum Dementia: Classification in Addition to Diagnosis. %A Emrani, Sheina %A Lamar, Melissa %A Price, Catherine C %A Wasserman, Victor %A Matusz, Emily %A Au, Rhoda %A Swenson, Rodney %A Nagele, Robert %A Heilman, Kenneth M %A Libon, David J %X

Alzheimer's disease (AD) and vascular dementia (VaD) are the two most common types of dementia. Although the combination of these disorders, called 'mixed' dementia, is recognized, the prevailing clinical and research perspective continues to consider AD and VaD as independent disorders. A review of recent neuropathological and neuropsychological literature reveals that these two disorders frequently co-occur and so-called 'pure' AD or VaD is comparatively rare. In addition, recent research shows that vascular dysfunction not only potentiates AD pathology, but that pathological changes in AD may subsequently induce vascular disorders. On the basis of these data, we propose that the neurobiological underpinnings underlying AD/VaD dementia and their neuropsychological phenotypes are best understood as existing along a clinical/pathological continuum or spectrum. We further propose that in conjunction with current diagnostic criteria, statistical modeling techniques using neuropsychological test performance should be leveraged to construct a system to classify AD/VaD spectrum dementia in order to test hypotheses regarding how mechanisms related to AD and VaD pathology interact and influence each other.

%B J Alzheimers Dis %V 73 %P 63-71 %8 2020 %G eng %N 1 %1 https://www.ncbi.nlm.nih.gov/pubmed/31815693?dopt=Abstract %R 10.3233/JAD-190654 %0 Journal Article %J J Alzheimers Dis %D 2018 %T Assessing Working Memory in Mild Cognitive Impairment with Serial Order Recall. %A Emrani, Sheina %A Libon, David J %A Lamar, Melissa %A Price, Catherine C %A Jefferson, Angela L %A Gifford, Katherine A %A Hohman, Timothy J %A Nation, Daniel A %A Delano-Wood, Lisa %A Jak, Amy %A Bangen, Katherine J %A Bondi, Mark W %A Brickman, Adam M %A Manly, Jennifer %A Swenson, Rodney %A Au, Rhoda %K Aged %K Aged, 80 and over %K Cognitive Dysfunction %K Executive Function %K Female %K Humans %K Male %K Memory Disorders %K Memory, Short-Term %K Mental Recall %K Neuropsychological Tests %K Regression Analysis %K Serial Learning %X

BACKGROUND: Working memory (WM) is often assessed with serial order tests such as repeating digits backward. In prior dementia research using the Backward Digit Span Test (BDT), only aggregate test performance was examined.

OBJECTIVE: The current research tallied primacy/recency effects, out-of-sequence transposition errors, perseverations, and omissions to assess WM deficits in patients with mild cognitive impairment (MCI).

METHODS: Memory clinic patients (n = 66) were classified into three groups: single domain amnestic MCI (aMCI), combined mixed domain/dysexecutive MCI (mixed/dys MCI), and non-MCI where patients did not meet criteria for MCI. Serial order/WM ability was assessed by asking participants to repeat 7 trials of five digits backwards. Serial order position accuracy, transposition errors, perseverations, and omission errors were tallied.

RESULTS: A 3 (group)×5 (serial position) repeated measures ANOVA yielded a significant group×trial interaction. Follow-up analyses found attenuation of the recency effect for mixed/dys MCI patients. Mixed/dys MCI patients scored lower than non-MCI patients for serial position 3 (p < 0.003) serial position 4 (p < 0.002); and lower than both group for serial position 5 (recency; p < 0.002). Mixed/dys MCI patients also produced more transposition errors than both groups (p < 0.010); and more omissions (p < 0.020), and perseverations errors (p < 0.018) than non-MCI patients.

CONCLUSIONS: The attenuation of a recency effect using serial order parameters obtained from the BDT may provide a useful operational definition as well as additional diagnostic information regarding working memory deficits in MCI.

%B J Alzheimers Dis %V 61 %P 917-928 %8 2018 %G eng %N 3 %1 http://www.ncbi.nlm.nih.gov/pubmed/29254087?dopt=Abstract %R 10.3233/JAD-170555 %0 Journal Article %J J Alzheimers Dis %D 2017 %T Age and Graphomotor Decision Making Assessed with the Digital Clock Drawing Test: The Framingham Heart Study. %A Piers, Ryan J %A Devlin, Kathryn N %A Ning, Boting %A Liu, Yulin %A Wasserman, Ben %A Massaro, Joseph M %A Lamar, Melissa %A Price, Catherine C %A Swenson, Rod %A Davis, Randall %A Penney, Dana L %A Au, Rhoda %A Libon, David J %X

BACKGROUND: Digital Clock Drawing Test (dCDT) technology enables the examination of detailed neurocognitive behavior as behavior unfolds in real time; a capability that cannot be obtained using a traditional pen and paper testing format.

OBJECTIVE: Parameters obtained from the dCDT were used to investigate neurocognitive constructs related to higher-order neurocognitive decision making and information processing speed. The current research sought to determine the effect of age as related to combined motor and non-motor components of drawing, and higher-order decision making latencies.

METHODS: A large group of stroke- and dementia- free Framingham Heart Study participants were administered the dCDT to command and copy with hands set for "10 after 11". Six age groups (age range 28-98) were constructed.

RESULTS: Differences between age groups were found for total time to completion, total pen stroke count, and higher-order decision making latencies in both command and copy test conditions.

CONCLUSION: Longer age-related decision making latencies may reflect a greater need for working memory and increased self-monitoring in older subjects. These latency measures have potential to serve as neurocognitive biomarkers of Alzheimer's disease and other insidious neurodegenerative disorders.

%B J Alzheimers Dis %V 60 %P 1611-1620 %8 2017 %G eng %N 4 %1 http://www.ncbi.nlm.nih.gov/pubmed/29036819?dopt=Abstract %R 10.3233/JAD-170444 %0 Journal Article %J J Alzheimers Dis %D 2017 %T Blood Pressure and Hispanic/Latino Cognitive Function: Hispanic Community Health Study/Study of Latinos Results. %A Tarraf, Wassim %A Rodríguez, Carlos J %A Daviglus, Martha L %A Lamar, Melissa %A Schneiderman, Neil %A Gallo, Linda %A Talavera, Gregory A %A Kaplan, Robert C %A Fornage, Myriam %A Conceicao, Alan %A González, Hector M %X

BACKGROUND: Hispanics/Latinos are at increased risk for cardiovascular disease and cognitive decline and dementias. High blood pressure (BP) has been implicated in both stroke and dementias. Associations between BP and cognition among diverse Latinos are still unpublished.

OBJECTIVE: We examined associations between cognition and four BP based measures among diverse Hispanics/Latinos. We hypothesized that higher BP, particularly systolic pressure, and increased arterial stiffness (i.e., pulse pressure), would be associated with lower cognitive function.

METHODS: We used baseline (2008-2011) Hispanic Community Health Study/Study of Latinos (HCHS/SOL; n = 9,019; ages 45-74 years) data to examine cognition in relation to BP measures.

RESULTS: In age, sex, and education adjusted models, systolic, pulse, and mean arterial pressure were consistently negatively associated with executive function, psychomotor speed and sustained attention, verbal episodic learning and memory, speech fluency, and mental status measures. These associations were attenuated but remained statistically significant in fully adjusted models.

CONCLUSION: Among middle-aged and older diverse Hispanics/Latinos, we found modest but consistent associations between indicators of arterial stiffness, and compromised blood flow and lower cognitive function. Clinical management and public health interventions to raise awareness and enhance BP management beginning in midlife could reduce disparities and improve population health by reducing cognitive decline burdens.

%B J Alzheimers Dis %V 59 %P 31-42 %8 2017 %G eng %N 1 %1 http://www.ncbi.nlm.nih.gov/pubmed/28582859?dopt=Abstract %R 10.3233/JAD-170017