%0 Journal Article %J J Alzheimers Dis %D 2023 %T Associations of the Harvard Automated Phone Task and Alzheimer's Disease Pathology in Cognitively Normal Older Adults: Preliminary Findings. %A Gonzalez, Christopher %A Mimmack, Kayden J %A Amariglio, Rebecca E %A Becker, J Alex %A Chhatwal, Jasmeer P %A Fitzpatrick, Colleen D %A Gatchel, Jennifer R %A Johnson, Keith A %A Katz, Zoe S %A Kuppe, Madeline K %A Locascio, Joseph J %A Udeogu, Onyinye J %A Papp, Kathryn V %A Premnath, Pranitha %A Properzi, Michael J %A Rentz, Dorene M %A Schultz, Aaron P %A Sperling, Reisa A %A Vannini, Patrizia %A Wang, Sharon %A Marshall, Gad A %K Activities of Daily Living %K Aged %K Alzheimer Disease %K Amyloid %K Amyloid beta-Peptides %K Amyloidogenic Proteins %K Cognitive Dysfunction %K Entorhinal Cortex %K Humans %K Positron-Emission Tomography %K tau Proteins %X

BACKGROUND: Detecting clinically meaningful changes in instrumental activities of daily living (IADL) at the earliest stages of Alzheimer's disease (AD) is critical.

OBJECTIVE: The objective of this exploratory study was to examine the cross-sectional relationship between a performance-based IADL test, the Harvard Automated Phone Task (APT), and cerebral tau and amyloid burden in cognitively normal (CN) older adults.

METHODS: Seventy-seven CN participants underwent flortaucipir tau and Pittsburgh Compound B amyloid PET. IADL were assessed using the three Harvard APT tasks: prescription refill (APT-Script), health insurance company call (APT-PCP), and bank transaction (APT-Bank). Linear regression models were used to determine associations between each APT task and entorhinal cortex, inferior temporal, or precuneus tau with or without an interaction with amyloid.

RESULTS: Significant associations were found between APT-Bank task rate and interaction between amyloid and entorhinal cortex tau, and APT-PCP task and interactions between amyloid and inferior temporal and precuneus tau. No significant associations were found between the APT tasks and tau or amyloid alone.

CONCLUSION: Our preliminary findings suggest an association between a simulated real-life IADL test and interactions of amyloid and several regions of early tau accumulation in CN older adults. However, some analyses were underpowered due to the small number of participants with elevated amyloid, and findings should be interpreted with caution. Future studies will further explore these associations cross-sectionally and longitudinally in order to determine whether the Harvard APT can serve as a reliable IADL outcome measure for preclinical AD prevention trials and ultimately in the clinic setting.

%B J Alzheimers Dis %V 94 %P 217-226 %8 2023 %G eng %N 1 %R 10.3233/JAD-220885 %0 Journal Article %J J Alzheimers Dis %D 2022 %T Association of Carotid Intima Media Thickening with Future Brain Region Specific Amyloid-β Burden. %A Baradaran, Hediyeh %A Peloso, Gina M %A Polak, Joseph F %A Killiany, Ronald J %A Ghosh, Saptaparni %A DeCarli, Charles S %A Thibault, Emma G %A Sperling, Reisa A %A Johnson, Keith A %A Beiser, Alexa %A Romero, Jose R %A Seshadri, Sudha %X

BACKGROUND: Carotid atherosclerosis is associated with cognitive impairment and dementia, though there is limited evidence of a direct link between carotid disease and amyloid-β (Aβ) burden.

OBJECTIVE: We studied the association of baseline and progressive carotid intima media thickness (CIMT) with Aβ on 11C-Pittsburgh Compound B (PiB) to determine if those with carotid atherosclerosis would have higher Aβ burden.

METHODS: We studied 47 participants from the Framingham Offspring cohort with carotid ultrasounds measuring CIMT at their 6th clinic examination (aged 49.5±5.7 years) and an average of 9.6 years later, and PiB imaging measuring Aβ on average 22.1 years post baseline. We used multivariate linear regression analyses to relate baseline, follow-up, mean, and progression of internal carotid artery (ICA) and common carotid artery (CCA) CIMT to Aβ in brain regions associated with Alzheimer's disease (AD) and related dementias (ADRD), adjusting for age, sex, and other vascular risk factors.

RESULTS: Participants with higher mean ICA IMT had more Aβ in the precuneus (beta±standard error [β±SE]: 0.466±0.171 mm, p = 0.01) and the frontal, lateral, and retrosplenial regions (β±SE: 0.392±0.164 mm, p = 0.022) after adjusting for age, sex, vascular risk factors, and medication use. We did not find an association between any CCA IMT measures and Aβ or progression of ICA or CCA IMT and Aβ.

CONCLUSION: Carotid atherosclerosis, as measured by ICA IMT, is associated with increased Aβ burden later in life. These findings support a link between vascular disease and AD/ADRD pathophysiology.

%B J Alzheimers Dis %V 89 %P 223-232 %8 2022 Aug 30 %G eng %N 1 %R 10.3233/JAD-215679 %0 Journal Article %J J Alzheimers Dis %D 2022 %T Associations Between Brainstem Volume and Alzheimer's Disease Pathology in Middle-Aged Individuals of the Framingham Heart Study. %A Jacobs, Heidi I L %A O'Donnell, Adrienne %A Satizabal, Claudia L %A Lois, Cristina %A Kojis, Daniel %A Hanseeuw, Bernard J %A Thibault, Emma %A Sanchez, Justin S %A Buckley, Rachel F %A Yang, Qiong %A DeCarli, Charles %A Killiany, Ron %A Sargurupremraj, Muralidharan %A Sperling, Reisa A %A Johnson, Keith A %A Beiser, Alexa S %A Seshadri, Sudha %X

The brainstem is among the first regions to accumulate Alzheimer's disease (AD)-related hyperphosphorylated tau pathology during aging. We aimed to examine associations between brainstem volume and neocortical amyloid-β or tau pathology in 271 middle-aged clinically normal individuals of the Framingham Heart Study who underwent MRI and PET imaging. Lower volume of the medulla, pons, or midbrain was associated with greater neocortical amyloid burden. No associations were detected between brainstem volumes and tau deposition. Our results support the hypothesis that lower brainstem volumes are associated with initial AD-related processes and may signal preclinical AD pathology.

%B J Alzheimers Dis %V 86 %P 1603-1609 %8 2022 Apr 19 %G eng %N 4 %R 10.3233/JAD-215372 %0 Journal Article %J J Alzheimers Dis %D 2022 %T Non-Alcoholic Fatty Liver Disease, Liver Fibrosis, and Regional Amyloid-β and Tau Pathology in Middle-Aged Adults: The Framingham Study. %A Weinstein, Galit %A O'Donnell, Adrienne %A Davis-Plourde, Kendra %A Zelber-Sagi, Shira %A Ghosh, Saptaparni %A DeCarli, Charles S %A Thibault, Emma G %A Sperling, Reisa A %A Johnson, Keith A %A Beiser, Alexa S %A Seshadri, Sudha %X

BACKGROUND: Liver steatosis and fibrosis are emerging as risk factors for multiple extrahepatic health conditions; however, their relationship with Alzheimer's disease pathology is unclear.

OBJECTIVE: To examine whether non-alcoholic fatty liver disease (NAFLD) and FIB-4, a non-invasive index of advanced fibrosis, are associated with brain amyloid-β (Aβ) and tau pathology.

METHODS: The study sample included Framingham Study participants from the Offspring and Third generation cohorts who attended exams 9 (2011-2014) and 2 (2008-2011), respectively. Participants underwent 11C-Pittsburgh Compound-B amyloid and 18F-Flortaucipir tau positron emission tomography (PET) imaging and abdomen computed tomography, or had information on all components of the FIB-4 index. Linear regression models were used to assess the relationship of NAFLD and FIB-4 with regional tau and Aβ, adjusting for potential confounders and multiple comparisons.

RESULTS: Of the subsample with NAFLD information (N = 169; mean age 52±9 y; 57% males), 57 (34%) had NAFLD. Of the subsample with information on liver fibrosis (N = 177; mean age 50±10 y; 51% males), 34 (19%) had advanced fibrosis (FIB-4 >  1.3). Prevalent NAFLD was not associated with Aβ or tau PET. However, FIB-4 index was significantly associated with increased rhinal tau (β= 1.03±0.33, p = 0.002). Among individuals with prevalent NAFLD, FIB-4 was related to inferior temporal, parahippocampal gyrus, entorhinal and rhinal tau (β= 2.01±0.47, p <  0.001; β= 1.60±0.53, p = 0.007, and β= 1.59±0.47, p = 0.003 and β= 1.60±0.42, p = 0.001, respectively) and to Aβ deposition overall and in the inferior temporal and parahippocampal regions (β= 1.93±0.47, p <  0.001; β= 1.59±0.38, p <  0.001, and β= 1.52±0.54, p = 0.008, respectively).

CONCLUSION: This study suggests a possible association between liver fibrosis and early Alzheimer's disease pathology, independently of cardio-metabolic risk factors.

%B J Alzheimers Dis %V 86 %P 1371-1383 %8 2022 Apr 05 %G eng %N 3 %R 10.3233/JAD-215409 %0 Journal Article %J J Alzheimers Dis %D 2021 %T Association of Midlife Depressive Symptoms with Regional Amyloid-β and Tau in the Framingham Heart Study. %A Gonzales, Mitzi M %A Samra, Jasmeet %A O'Donnell, Adrienne %A Mackin, R Scott %A Salinas, Joel %A Jacob, Mini %A Satizabal, Claudia L %A Aparicio, Hugo J %A Thibault, Emma G %A Sanchez, Justin S %A Finney, Rebecca %A Rubinstein, Zoe B %A Mayblyum, Danielle V %A Killiany, Ron J %A Decarli, Charlie S %A Johnson, Keith A %A Beiser, Alexa S %A Seshadri, Sudha %X

BACKGROUND: Depressive symptoms predict increased risk for dementia decades before the emergence of cognitive symptoms. Studies in older adults provide preliminary evidence for an association between depressive symptoms and amyloid-β (Aβ) and tau accumulation. It is unknown if similar alterations are observed in midlife when preventive strategies may be most effective.

OBJECTIVE: The study aim was to evaluate the association between depressive symptoms and cerebral Aβ and tau in a predominately middle-aged cohort with examination of the apolipoprotein (APOE) ɛ4 allele as a moderator.

METHODS: Participants included 201 adults (mean age 53±8 years) who underwent 11C-Pittsburgh Compound B amyloid and 18F-Flortaucipir tau positron emission tomography (PET) imaging. Depressive symptoms were evaluated with the Center for Epidemiological Studies Depression Scale (CES-D) at the time of PET imaging, as well as eight years prior. Associations between depressive symptoms at both timepoints, as well as depression (CES-D≥16), with regional Aβ and tau PET retention were evaluated with linear regression adjusting for age and sex. Interactions with the APOE ɛ4 allele were explored.

RESULTS: Depressive symptoms and depression were not associated with PET outcomes in the overall sample. However, among APOE ɛ4 allele carriers, there was a significant cross-sectional association between depressive symptoms and increased tau PET uptake in the entorhinal cortex (β= 0.446, SE = 0.155, p = 0.006) and amygdala (β= 0.350, SE = 0.133, p = 0.012).

CONCLUSION: Although longitudinal studies are necessary, the results suggest that APOE ɛ4 carriers with depressive symptoms may present with higher susceptibility to early tau accumulation in regions integral to affective regulation and memory consolidation.

%B J Alzheimers Dis %V 82 %P 249-260 %8 2021 Jun 29 %G eng %N 1 %R 10.3233/JAD-210232 %0 Journal Article %J J Alzheimers Dis %D 2020 %T Examining Cognitive Decline Across Black and White Participants in the Harvard Aging Brain Study. %A Amariglio, Rebecca E %A Buckley, Rachel F %A Rabin, Jennifer S %A Papp, Kathryn V %A Quiroz, Yakeel T %A Mormino, Elizabeth C %A Sparks, Kathryn P %A Johnson, Keith A %A Rentz, Dorene M %A Sperling, Reisa A %X

BACKGROUND: Black Americans are approximately twice as likely to develop dementia as compared to White Americans and the magnitude of this disparity is often attributed to a variety of factors that include psychosocial and vascular risk factors. However, less is known about the potential contribution of Alzheimer's disease pathological differences.

OBJECTIVE: To examine potential differences incross-sectional and longitudinal cognitive performance in black and white participants who were clinically normal at baseline.

METHODS: 296 participants (48 African-American/black participants) underwent MRI and amyloid PET at baseline. Linear mixed models were used to examine the main effects of race, years of education, reading ability, Framingham Heart Study cardiovascular risk score (FHS-CVD), white matter hyperintensities (WMH), and amyloid (Aβ) burden on the Preclinical Alzheimer Cognitive Composite-5 (PACC5).

RESULTS: Lower levels of educationalattainment and reading ability were found for blacks compared to whites. By contrast, no differences in FHS-CVD, WMH, or Aβ were found by racial group. Baseline differences in PACC5 score were attenuated after adjusting for educationalfactors, vascular factors, and Aβ, but remained lower for blacks compared to whites (β= -0.24, p = 0.014). Further, blacks demonstrated a faster rate of PACC5 decline longitudinally compared to whites (β  = -0.055, p = 0.025) after adjusting for covariates.

CONCLUSION: Accounting for educationalfactors, vascular factors, and Aβ burden diminished, but did not eliminate, racial differences in PACC5 performance longitudinally. Understanding potential differences in longitudinal cognitive outcomes by race may be important for upcoming secondary prevention trials.

%B J Alzheimers Dis %V 75 %P 1437-1446 %8 2020 Jun 16 %G eng %N 4 %R 10.3233/JAD-191291 %0 Journal Article %J J Alzheimers Dis %D 2019 %T An UNC5C Allele Predicts Cognitive Decline and Hippocampal Atrophy in Clinically Normal Older Adults. %A Yang, Hyun-Sik %A Chhatwal, Jasmeer P %A Xu, Jishu %A White, Charles C %A Hanseeuw, Bernard %A Rabin, Jennifer S %A Papp, Kathryn V %A Buckley, Rachel F %A Schultz, Aaron P %A Properzi, Michael J %A Gatchel, Jennifer R %A Amariglio, Rebecca E %A Donovan, Nancy J %A Mormino, Elizabeth C %A Hedden, Trey %A Marshall, Gad A %A Rentz, Dorene M %A Johnson, Keith A %A De Jager, Philip L %A Sperling, Reisa A %X

BACKGROUND: The UNC5C rs3846455G allele has been linked to poor cognitive resilience against age-related neuropathologies, but this association remains to be replicated, and the allele's effect on hippocampal neurodegeneration needs to be examined.

OBJECTIVE: To further validate the association between rs3846455G and faster cognitive decline, especially among cognitively normal older adults, and to assess whether rs3846455G predicts accelerated hippocampal volume loss in older adults.

METHODS: We assessed participants in the Harvard Aging Brain Study (HABS), a longitudinal cohort study of older adults who were clinically normal at baseline. To avoid bias from population admixture, analyses were limited to participants of European descent with longitudinal neuroimaging data (n = 174). Linear mixed effect models were used to examine the effect of rs3846455G on longitudinal change of the Preclinical Alzheimer Cognitive Composite (PACC) and MRI-measured bilateral hippocampal volume, adjusting for baseline amyloid-β (Aβ) measured by the cortical Pittsburgh Compound B PET distributed volume ratio. We also tested whether hippocampal atrophy mediates the association between rs3846455G and greater PACC decline through a mediation analysis.

RESULTS: rs3846455G was associated with greater PACC decline (β= -0.087/year, 95% CI -0.169 to -0.005, p = 0.039) after controlling for baseline Aβ. Further, rs3846455G predicted accelerated hippocampal atrophy after controlling for baseline Aβ (β= -57.3 mm3/year, 95% CI -102.8 to -11.9, p = 0.014). The association between rs3846455G and greater PACC decline was partially mediated by accelerated hippocampal atrophy (mediated effect (relative scale) = -0.014, 95% CI -0.032 to -6.0×10-4, p = 0.039).

CONCLUSION: UNC5C rs3846455G predicts greater cognitive decline and accelerated hippocampal atrophy in clinically normal older adults.

%B J Alzheimers Dis %V 68 %P 1161-1170 %8 2019 Apr 8 %G eng %N 3 %R 10.3233/JAD-180788 %0 Journal Article %J J Alzheimers Dis %D 2018 %T 18F-Flortaucipir Binding in Choroid Plexus: Related to Race and Hippocampus Signal. %A Lee, Christopher M %A Jacobs, Heidi I L %A Marquié, Marta %A Becker, John A %A Andrea, Nicolas V %A Jin, David S %A Schultz, Aaron P %A Frosch, Matthew P %A Gómez-Isla, Teresa %A Sperling, Reisa A %A Johnson, Keith A %X

BACKGROUND: On target 18F-Flortaucipir (FTP) binding of Alzheimer's disease tau aggregates and off-target binding of melanocytes have been demonstrated with autoradiography.

OBJECTIVE: We aimed to investigate the hypothesis that if binding in choroid plexus (CP) is due to melanocytes, the signal would be elevated in Black/African American (B/AA) compared to White (W) participants. In addition, we examined whether CP signal affects measurements in adjacent regions, and whether correcting for spill-in effects has an influence on associations between hippocampus (HC) FTP and amyloid or cognition.

METHODS: FTP race differences in 147 Harvard Aging Brain Study participants (23 B/AA, 124W) were examined in CP, HC, HC covaried for CP, amygdala, inferior temporal gyrus, entorhinal cortex, and fusiform regions. Associations between CP FTP and other regions-of-interest (ROIs) were probed to assess spill-in effects. A statistical regression approach to attenuate CP spill-in was tested by relating adjusted HC SUVR residuals and unadjusted HC SUVR to race, cognition and amyloid. All analyses were covaried for age, sex, education and amyloid deposition, and Bonferroni-corrected for multiple comparisons.

RESULTS: B/AA individuals had elevated CP and HC SUVR (p < 0.007), whereas other ROI SUVR and HC SUVR covaried for CP SUVR did not show race differences (p > 0.05). CP SUVR was associated with HC SUVR (p < 10-14), but with no other ROI SUVR (p > 0.05). When adjusting HC SUVR for CP SUVR, no race differences in residual HC SUVR were detected, and relationships with amyloid and memory became apparent.

CONCLUSION: Melanocyte FTP binding may account partially for high CP signal. This off-target binding affects mainly HC FTP measurements, which should be interpreted with caution.

%B J Alzheimers Dis %V 62 %P 1691-1702 %8 2018 %G eng %N 4 %1 http://www.ncbi.nlm.nih.gov/pubmed/29614677?dopt=Abstract %R 10.3233/JAD-170840 %0 Journal Article %J J Alzheimers Dis %D 2017 %T Alzheimer's Disease Biomarkers and Future Decline in Cognitive Normal Older Adults. %A Dumurgier, Julien %A Hanseeuw, Bernard J %A Hatling, Frances B %A Judge, Kelly A %A Schultz, Aaron P %A Chhatwal, Jasmeer P %A Blacker, Deborah %A Sperling, Reisa A %A Johnson, Keith A %A Hyman, Bradley T %A Gómez-Isla, Teresa %X

BACKGROUND: Identifying older adults at risk of cognitive decline represents a challenge as Alzheimer's disease (AD) modifying therapies move toward preclinical stages.

OBJECTIVE: To investigate the relationship between AD biomarkers and subsequent change in cognition in a cohort of cognitively intact older adults.

METHODS: 84 cognitively normal subjects (mean age 72.0 years, 59% women) were recruited through the Massachusetts Alzheimer's Disease Research Center and the Harvard Aging Brain Study and followed over 3 years. Measurements of amyloid-β 1-42 (Aβ42), total Tau (t-Tau), and Tau phosphorylated at threonine 181 (p-Tau181) in the cerebrospinal fluid (CSF) at study entry were available in all cases. Baseline brain MRI, FDG-PET, and PiB-PET data were available in the majority of participants. Relationship between baseline AD biomarkers and longitudinal change in cognition was assessed using Cox proportional hazard regression and linear mixed models.

RESULTS: 14% participants increased their global Clinical Dementia Rating (CDR) score from 0 to 0.5 during follow-up. A CDR score increase was associated with higher baseline CSF t-Tau and p-Tau181, higher global cortical PiB retention, and lower hippocampal volume. The combination of high CSF t-Tau and low Aβ42 or low hippocampal volume was more strongly related to cognitive outcome than each single biomarker. Higher CSF t-Tau was the only biomarker associated with subsequent decline in MMSE score.

CONCLUSIONS: Baseline CSF t-Tau and p-Tau181, in vivo amyloid load, and hippocampal volume were all independently associated with future decline in cognition. The discriminatory ability of these biomarkers to predict risk of cognitive decline, however, was only modest.

%B J Alzheimers Dis %V 60 %P 1451-1459 %G eng %N 4 %R 10.3233/JAD-170511 %0 Journal Article %J J Alzheimers Dis %D 2017 %T Depressive Symptoms and Tau Accumulation in the Inferior Temporal Lobe and Entorhinal Cortex in Cognitively Normal Older Adults: A Pilot Study. %A Gatchel, Jennifer R %A Donovan, Nancy J %A Locascio, Joseph J %A Schultz, Aaron P %A Becker, J Alex %A Chhatwal, Jasmeer %A Papp, Kathryn V %A Amariglio, Rebecca E %A Rentz, Dorene M %A Blacker, Deborah %A Sperling, Reisa A %A Johnson, Keith A %A Marshall, Gad A %X

BACKGROUND: Depressive symptoms are common in older adults and associated with increased morbidity and cognitive decline. These symptoms occur during preclinical and prodromal stages of Alzheimer's disease (AD), but their relationship to tau, one of the main AD proteinopathies, is poorly understood.

OBJECTIVE: The objective of this study was to investigate the cross-sectional association between depressive symptoms and cerebral tau [18F T807 (also known as 18F-AV-1451) tau positron emission tomography (PET) imaging] in cognitively normal (CN) older adults.

METHODS: We measured depressive symptoms using the Geriatric Depression Scale (GDS), and in vivo cerebral tau using T807 PET in 111 CN older adults. We employed general linear regression models to evaluate the relationship of GDS score regressed on entorhinal cortex (EC) or inferior temporal (IT) tau in separate backward elimination models. Other predictors included age, sex, and in secondary analyses, amyloid (Pittsburgh Compound B PET).

RESULTS: Higher GDS was significantly associated with greater IT tau (partial r = 0.188, p = 0.050) and marginally associated with greater EC tau (partial r = 0.183, p = 0.055). In additional analyses including both linear and quadratic age terms, we found a significant U-shaped relation of GDS to age (p = 0.001).

CONCLUSIONS: Results suggest that IT and EC tau are modestly associated with depressive symptoms in CN older adults. Findings suggest a link between depressive symptoms and tau-mediated neurodegeneration in a region vulnerable in AD. Future longitudinal studies examining the association of more severe depressive symptoms and cerebral tau accumulation are needed to substantiate this finding and to guide prevention and treatment in AD.

%B J Alzheimers Dis %V 59 %P 975-985 %8 2017 %G eng %N 3 %1 http://www.ncbi.nlm.nih.gov/pubmed/28697559?dopt=Abstract %R 10.3233/JAD-170001 %0 Journal Article %J J Alzheimers Dis %D 2016 %T Lower Late-Life Body-Mass Index is Associated with Higher Cortical Amyloid Burden in Clinically Normal Elderly. %A Hsu, David C %A Mormino, Elizabeth C %A Schultz, Aaron P %A Amariglio, Rebecca E %A Donovan, Nancy J %A Rentz, Dorene M %A Johnson, Keith A %A Sperling, Reisa A %A Marshall, Gad A %X

BACKGROUND: Lower body-mass index (BMI) in late life has been associated with an increased risk of dementia, and weight loss has been associated with more rapid decline in Alzheimer's disease (AD) dementia.

OBJECTIVE: To explore the association between BMI and cortical amyloid burden in clinically normal (CN) elderly at risk for AD dementia.

METHODS: Cross-sectional analyses were completed using baseline data from the Harvard Aging Brain Study, consisting of 280 community-dwelling CN older adults aged 62-90. Assessments included medical histories and physical exam, Pittsburgh compound B (PiB) positron emission tomography (PET) amyloid imaging, and apolipoprotein E ɛ4 (APOE4) genotyping. For the primary analysis, a general linear regression model was used to evaluate the association of BMI with PiB retention. Covariates included age, sex, years of education, and APOE4 carrier status. Secondary analyses were performed for BMI subdivisions (normal, overweight, obese), APOE4 carriers, and BMI×APOE4 interaction.

RESULTS: In the primary analysis, greater PiB retention was associated with lower BMI (β  =  -0.14, p = 0.02). In the secondary analyses, APOE4 carrier status (β= -0.27, p = 0.02) and normal BMI (β= -0.25, p = 0.01), as opposed to overweight or obese BMI, were associated with greater PiB retention. The BMI×APOE4 interaction was also significant (β= -0.14, p = 0.04).

CONCLUSIONS: This finding offers new insight into the role of BMI at the preclinical stage of AD, wherein lower BMI late in life is associated with greater cortical amyloid burden. Future studies are needed to elucidate the mechanism behind this association, especially in those with lower BMI who are APOE4 carriers.

%B J Alzheimers Dis %V 53 %P 1097-105 %8 2016 Jun 18 %G eng %N 3 %1 http://www.ncbi.nlm.nih.gov/pubmed/27340843?dopt=Abstract %R 10.3233/JAD-150987 %0 Journal Article %J J Alzheimers Dis %D 2015 %T Depressive Symptoms and Biomarkers of Alzheimer's Disease in Cognitively Normal Older Adults. %A Donovan, Nancy J %A Hsu, David C %A Dagley, Alexander S %A Schultz, Aaron P %A Amariglio, Rebecca E %A Mormino, Elizabeth C %A Okereke, Olivia I %A Rentz, Dorene M %A Johnson, Keith A %A Sperling, Reisa A %A Marshall, Gad A %X

Even low levels of depressive symptoms are associated with an increased risk of cognitive decline in older adults without overt cognitive impairment (CN). Our objective was to examine whether very low, "subthreshold symptoms of depression" are associated with Alzheimer's disease (AD) biomarkers of neurodegeneration in CN adults and whether these associations are specific to particular depressive symptoms. We analyzed data from 248 community-dwelling CN older adults, including measurements of cortical amyloid burden, neurodegeneration markers of hippocampal volume (HV) and cerebral 18F-fluorodeoxyglucose (FDG) metabolism in a composite of AD-related regions and the 30-item Geriatric Depression Scale (GDS). Participants with GDS >10 were excluded. General linear regression models evaluated the cross-sectional relations of GDS to HV or FDG in separate backward elimination models. Predictors included GDS total score, age, gender, premorbid intelligence, a binary amyloid variable and its interaction with GDS. Principal component analyses of GDS item scores revealed three factors (the Dysphoria, Apathy-Anhedonia, and Anxiety-Concentration Factors). In secondary analyses, GDS total score was replaced with the three factor scores in repeated models. Higher GDS score (p = 0.03) was significantly associated with lower HV and was marginally related (p = 0.06) to FDG hypometabolism. In secondary models, higher Dysphoria (p = 0.02) and Apathy-Anhedonia (p = 0.05) were related to lower HV while higher Apathy-Anhedonia (p = 0.003) was the sole factor related to FDG hypometabolism. Amyloid was not a significant predictor in any model. In conclusion, very low-level dysphoria, apathy and anhedonia may point to neurodegeneration in AD-related regions but this association appears to be independent of amyloid burden.

%B J Alzheimers Dis %8 2015 Feb 19 %G eng %R 10.3233/JAD-142940