Journal of Alzheimer's Disease - Volume 65, issue 2

Authors: Gomez, Gabriela | Beason-Held, Lori L. | Bilgel, Murat | An, Yang | Wong, Dean F. | Studenski, Stephanie | Ferrucci, Luigi | Resnick, Susan M.

Article Type: Research Article

Abstract: Background: Recent studies show links between metabolic syndrome and Alzheimer’s disease (AD) neuropathology. Understanding the link between vascular-related health conditions and dementia will help target at risk populations and inform clinical strategies for early detection and prevention of AD. Objective: To determine whether metabolic syndrome is associated with global cerebral amyloid-β (Aβ) positivity and longitudinal Aβ accumulation. Methods: Prospective study of 165 participants who underwent (11)C-Pittsburgh compound B (PiB) PET neuroimaging to measure Aβ, from June 2005 to May 2016. Metabolic syndrome was defined using the revised Third Adults Treatment Panel of the National Cholesterol Education …Program criteria. Participants were classified as PiB+/–. Linear mixed effects models assessed the relationships between baseline metabolic syndrome and PiB status and regional Aβ change over time. Results: A total of 165 cognitively normal participants of the Baltimore Longitudinal Study of Aging (BLSA) Neuroimaging substudy, aged 55–92 years (mean baseline age = 76.4 years, 85 participants were male), received an average of 2.5 PET-PiB scans over an average interval of 2.6 (3.08 SD) years between first and last visits. Metabolic syndrome was not associated with baseline PiB positivity or concurrent regional Aβ. Metabolic syndrome was associated with increased rates of Aβ accumulation in superior parietal and precuneus regions over time in the PiB+ group. Elevated fasting glucose and blood pressure showed individual associations with accelerated Aβ accumulation. Conclusion: Metabolic syndrome was associated with accelerated Aβ accumulation in PiB+ individuals and may be an important factor in the progression of AD pathology. Show more

Keywords: Alzheimer’s disease, amyloid PET, brain, cholesterol, dementia, diabetes, hypertension, metabolic syndrome, vascular

DOI: 10.3233/JAD-180297

Citation: Journal of Alzheimer's Disease, vol. 65, no. 2, pp. 629-639, 2018

Authors: Lee, Juyoun | Cho, Hanna | Jeon, Seun | Kim, Hee Jin | Kim, Yeo Jin | Lee, Jeongmin | Kim, Sung Tae | Lee, Jong-Min | Chin, Juhee | Lockhart, Samuel N. | Lee, Ae Young | Na, Duk L. | Seo, Sang Won

Article Type: Research Article

Abstract: Background: Sex effects on the progression of Alzheimer’s disease (AD) have received less attention than other demographic factors, including onset age and education. Objective: The aim of this study was to investigate whether sex affected cortical thinning in the disease progression of AD. Methods: We prospectively recruited 36 patients with early-stage AD and 14 people with normal cognition. All subjects were assessed with magnetic resonance imaging at baseline, Year 1, Year 3, and Year 5. We performed cortical thickness analyses using surface-based morphometry on magnetic resonance imaging. Results: Women with AD showed more rapid …cortical thinning in the left dorsolateral frontal cortex, left superior temporal gyrus, bilateral temporo-parietal association cortices, bilateral anterior cingulate gyri, bilateral medial frontal cortices, and bilateral occipital cortices over 5 years than men with AD, even though there was no difference in cortical thickness at baseline. In contrast, there were no regions of significantly more rapid atrophy in men with AD. Conclusions: Our findings suggest that women deteriorate faster than men in the progression of AD. Show more

Keywords: Alzheimer’s disease, cognitive reserve, cortical thickness, longitudinal study, sex

DOI: 10.3233/JAD-180049

Citation: Journal of Alzheimer's Disease, vol. 65, no. 2, pp. 641-649, 2018

Authors: Lim, Eun-Ye | Yang, Dong-Won | Cho, A-Hyun | Shim, Yong S.

Article Type: Research Article

Abstract: Background/Objective: Vascular risk factors and neurovascular dysfunction may be closely related to cognitive impairment and dementia. In this study, we evaluated the association between hemodynamic markers and longitudinal cognitive changes in patients with mild cognitive impairment (MCI). Furthermore, we investigated whether hemodynamic markers could predict the risk of progression to Alzheimer’s disease (AD) in patients with MCI. Methods: A total of 68 subjects with amnestic MCI were recruited. Using transcranial Doppler (TCD) ultrasonography, cerebrovascular reactivity was evaluated with a breath-holding test (breath holding index; BHI) in addition to the mean flow velocity (MFV) and pulsatility index (PI) of …the middle cerebral artery. We followed subjects for 24 months and each subject underwent neuropsychological testing and TCD ultrasonography, annually. According to the follow-up neuropsychological studies and clinical interviews at 12 months, we divided the patients with MCI into two groups: patients with stable cognitive performance and patients who progressed to AD. Results: Lower BHI and higher PI were observed in patients who progressed to AD. The changes of MMSE score over the first 12 months correlated with lower baseline MMSE score and changes of MFV and BHI. The changes of MMSE score over 24 months were closely related to higher baseline resistance index and PI values. Multivariate logistic regression showed that abnormal baseline BHI value could predict a conversion from MCI to AD. Conclusions: We confirmed there is a close association between hemodynamic changes represented by TCD markers and cognitive decline, supporting the clinical value of hemodynamic markers in predicting MCI patients who will progress to AD. Show more

Keywords: Alzheimer’s disease, cerebrovascular disease, mild cognitive impairment, stroke, ultrasound

DOI: 10.3233/JAD-180026

Citation: Journal of Alzheimer's Disease, vol. 65, no. 2, pp. 651-657, 2018

Authors: Zolochevska, Olga | Bjorklund, Nicole | Woltjer, Randall | Wiktorowicz, John E. | Taglialatela, Giulio

Article Type: Research Article

Abstract: Some individuals, here referred to as Non-Demented with Alzheimer’s Neuropathology (NDAN), retain their cognitive function despite the presence of amyloid plaques and tau tangles typical of symptomatic Alzheimer’s disease (AD). In NDAN, unlike AD, toxic amyloid-β oligomers do not localize to the postsynaptic densities (PSDs). Synaptic resistance to amyloid-β in NDAN may thus enable these individuals to remain cognitively intact despite the AD-like pathology. The mechanism(s) responsible for this resistance remains unresolved and understanding such protective biological processes could reveal novel targets for the development of effective treatments for AD. The present study uses a proteomic approach to compare the …hippocampal postsynaptic densities of NDAN, AD, and healthy age-matched persons to identify protein signatures characteristic for these groups. Subcellular fractionation followed by 2D gel electrophoresis and mass spectrometry were used to analyze the PSDs. We describe fifteen proteins which comprise the unique proteomic signature of NDAN PSDs, thus setting them apart from control subjects and AD patients. Show more

Keywords: Alzheimer’s disease, non-demented with AD-like pathology, postsynaptic density proteome, synapse

DOI: 10.3233/JAD-180179

Citation: Journal of Alzheimer's Disease, vol. 65, no. 2, pp. 659-682, 2018

Authors: Guerrero-Berroa, Elizabeth | Ravona-Springer, Ramit | Schmeidler, James | Heymann, Anthony | Soleimani, Laili | Sano, Mary | Leroith, Derek | Preiss, Rachel | Zukran, Ruth | Silverman, Jeremy M. | Beeri, Michal Schnaider

Article Type: Research Article

Abstract: Background: Type 2 diabetes (T2D) is a metabolic condition associated with poor clinical and cognitive outcomes including vascular disease, depressive symptoms, cognitive impairment, and dementia. In the general elderly population, depression has been consistently identified as a risk factor for cognitive impairment/decline. However, the association between depression and cognitive function in T2D has been understudied. Objective: We investigated the association between depression and cognitive function in a large sample of cognitively normal elderly with T2D. Methods: In this cross-sectional study, we examined 738 participants, aged 65–88 years old, enrolled in the Israel Diabetes and Cognitive Decline …study. For each cognitive domain (Episodic Memory, Executive Function, Attention/Working Memory, Language/Semantic Categorization) and Overall Cognition, multiple linear regressions assessed its association with depression (score greater than 5 on the 15-item version of the Geriatric Depression Scale [GDS]), adjusting for age, sex, and education. Results: Depression (n  = 66, 8.9%) was associated with worse performance on tasks of Executive Function (p  = 0.004), Language/Semantic Categorization (p  < 0.001), and Overall Cognition (p  < 0.002), but not Episodic Memory (p  = 0.643) or Attention/Working Memory (p  = 0.488). Secondary analyses using GDS as a continuous variable did not substantially change the results. Adjusting also for a history of antidepressant medication use slightly weakened the findings. Conclusion: Significant associations of depression with several cognitive domains and Overall Cognition even in cognitively normal elderly with T2D, suggest that depression may have a role in impaired cognitive function in T2D, which may be attenuated by antidepressants. Show more

Keywords: Cognitive domains, cognitive function, depressive symptoms, diabetes

DOI: 10.3233/JAD-170778

Citation: Journal of Alzheimer's Disease, vol. 65, no. 2, pp. 683-692, 2018