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

Authors: Steffen, Johannes | Stenzel, Jan | Ibrahim, Saleh | Pahnke, Jens

Article Type: Research Article

Abstract: Reduction of mitochondrial activity is a subtle and early event in the pathogenesis of Alzheimer’s disease. Mitochondrial damage and consequentially enhanced production of reactive oxygen species is particularly occurring in the vicinity of amyloid plaques. Since all cells are affected by mitochondrial damage, analyses of cell type-specific effects are challenging. To study the impact of mitochondrial alterations on microglial activity in a homogeneous genetic background, we generated bone marrow chimeras of irradiated 46-days-old APP-transgenic mice. For reconstitution, bone marrow from CX3CR1-eGFP mice with mitochondria of either non-obese diabetic or C57BL/6J animals was utilized. Successful reconstitution was evident in 100-day-old animals, …by the presence of eGFP-positive cells in liver and spleen. In the brain, one-third of IBA1-positive microglia cells were newly recruited eGFP-expressing cells. Although donor-derived microglia were equally located in the proximity of amyloid plaques, no difference was observed in either the amyloid level, total number, or microglial coverage of plaques. These results indicate that during this brief and early phase of amyloid deposition, beneficial mitochondrial alterations in the newly recruited third of microglial cells were not sufficient to affect the amyloidosis in APP-transgenic mice. Show more

Keywords: Alzheimer’s disease, amyloid-β, bone marrow cells, CX3CR1, microglia, neurodegenerative diseases, neuropathology, rodent models, spleen

DOI: 10.3233/JAD-180395

Citation: Journal of Alzheimer's Disease, vol. 65, no. 2, pp. 465-474, 2018

Authors: Musaeus, Christian Sandøe | Nielsen, Malene Schjønning | Østerbye, Natascha Nellum | Høgh, Peter

Article Type: Research Article

Abstract: Background: Electroencephalography (EEG) power has previously been used to compare mild cognitive impairment (MCI) patients who progress to Alzheimer’s disease (pMCI) with patients with MCI who remain stable (sMCI) by using beta power. However, the beta band is very broad and smaller frequency bands may improve accuracy. Objective: In the present study, we wanted to investigate whether it was possible to find any differences between pMCI and sMCI using relative power and whether these differences were correlated to cognitive function or neuropathology markers. Methods: 17 patients with AD, 27 patients with MCI, and 38 older healthy …controls were recruited from two memory clinics and followed for three years. EEGs were recorded at baseline for all participants and relative power was calculated. All participants underwent adjusted batteries of standardized cognitive tests and lumbar puncture. Results: We found that pMCI showed decreased baseline relative power in the parietal electrodes in the beta1 band (13–17.99 Hz). At 2-year follow-up, we found changes in all baseline beta bands but most pronounced in the beta1 band. In addition, we found that qEEG parietal power was correlated with amyloid-β 42 and anterograde memory. Conclusion: These findings suggests that relative power in the parietal electrodes in the beta1 band may be a better way to discriminate between pMCI and sMCI at the time of diagnosis than the broad beta band. Similar findings have also been found with resting state fMRI. In addition, we found that anterograde memory was correlated to qEEG parietal beta1 power. Show more

Keywords: Alzheimer’s disease, EEG, mild cognitive impairment, progression

DOI: 10.3233/JAD-180384

Citation: Journal of Alzheimer's Disease, vol. 65, no. 2, pp. 475-487, 2018

Authors: Fanning, Laura | Ryan-Atwood, Taliesin E. | Bell, J. Simon | Meretoja, Atte | McNamara, Kevin P. | Dārziņš, Pēteris | Wong, Ian C.K. | Ilomäki, Jenni

Article Type: Research Article

Abstract: Background: Differences in management and outcomes of oral anticoagulant (OAC) use may exist for people with and without dementia or cognitive impairment (CI). Objective: To systematically review the prevalence and safety and effectiveness outcomes of OAC use in people with and without dementia or CI. Methods: MEDLINE, EMBASE, and CINAHL were searched for studies reporting prevalence or safety and effectiveness outcomes of OAC use for people with and without dementia, published between 2000 to September 2017. Study selection, data extraction, and quality assessment were performed by two reviewers. Results: studies met pre-specified inclusion criteria …(21 prevalence studies, 6 outcomes studies). People with dementia had 52% lower odds of receiving OAC compared to people without dementia. Mean OAC prevalence was 32% for people with dementia, compared to 48% without dementia. There was no difference in the composite outcome of embolic events, myocardial infarction, and all-cause death between dementia and non-dementia groups (adjusted hazard ratio (HR) 0.72, 95% CI, 0.45–1.14, p  = 0.155). Bleeding rate was lower for people without dementia (HR 0.56, 95% CI, 0.37–0.85). Adverse warfarin events were more common for residents of long-term care with dementia (adjusted incidence rate ratio 1.48, 95% CI, 1.20–1.82). Community-dwelling people with dementia treated with warfarin had poorer anticoagulation control than those without dementia (mean time in therapeutic range (TTR) % ±SD, 38±26 (dementia), 61±27 (no dementia), p  < 0.0001). Conclusion: A lower proportion of people with dementia received oral anticoagulation compared with people without dementia. People with dementia had higher bleeding risk and poorer anticoagulation control when treated with warfarin. Show more

Keywords: Anticoagulant, atrial fibrillation, cognitive impairment, dementia, hemorrhage, ischemic stroke, prevalence, warfarin

DOI: 10.3233/JAD-180219

Citation: Journal of Alzheimer's Disease, vol. 65, no. 2, pp. 489-517, 2018

Authors: Slegers, Antoine | Filiou, Renée-Pier | Montembeault, Maxime | Brambati, Simona Maria

Article Type: Research Article

Abstract: The language changes that occur over the course of Alzheimer’s disease (AD) can impact communication abilities and have profound functional consequences. Picture description tasks can be used to approximate everyday communication abilities of AD patients. As various methods and variables have been studied over the years, current knowledge about the most affected features of AD discourse in the context of picture descriptions is difficult to summarize. This systematic review aims to provide researchers with an overview of the most common areas of impairment in AD discourse as they appear in picture description tasks. Based on the 44 articles fulfilling inclusion …criteria, our findings reflect a multidimensional pattern of changes in the production (speech rate), syntactic (length of utterance), lexical (word-frequency and use of pronouns), fluency (repetitions and word-finding difficulties), semantic (information units), and discourse (efficiency) domains. We discuss our findings in the light of current research and point to potential scientific and clinical uses of picture description tasks in the context of AD. Show more

Keywords: Alzheimer’s disease, language tests, psycholinguistics, systematic review

DOI: 10.3233/JAD-170881

Citation: Journal of Alzheimer's Disease, vol. 65, no. 2, pp. 519-542, 2018

Authors: Lazarou, Ioulietta | Adam, Katerina | Georgiadis, Kostas | Tsolaki, Anthoula | Nikolopoulos, Spiros | (Yiannis) Kompatsiaris, Ioannis | Tsolaki, Magda

Article Type: Research Article

Abstract: Background: Studies on subjective cognitive impairment (SCI) and neural activation report controversial results. Objective: To evaluate the ability to disentangle the differences of visual N170 ERP, generated by facial stimuli (Anger & Fear) as well as the cognitive deterioration of SCI, mild cognitive impairment (MCI), and Alzheimer’s disease (AD) compared to healthy controls (HC). Method: 57 people took part in this study. Images corresponding to facial stimuli of “Anger” and “Fear” were presented to 12 HC, 14 SCI, 17 MCI and 14 AD participants. EEG data were recorded by using a HD-EEG HydroCel with 256 channels. …Results: Results showed that the amplitude of N170 can contribute in distinguishing the SCI group, since statistically significant differences were observed with the HC (p < 0.05) and the MCI group from HC (p < 0.001), as well as AD from HC (p = 0.05) during the processing of facial stimuli. Noticeable differences were also observed in the topographic distribution of the N170 amplitude, while localization analysis by using sLORETA images confirmed the activation of superior, middle-temporal, and frontal lobe brain regions. Finally, in the case of “Fear”, SCI and HC demonstrated increased activation in the orbital and inferior frontal gyrus, respectively, MCI in the inferior temporal gyrus, and AD in the lingual gyrus. Conclusion: These preliminary findings suggest that the amplitude of N170 elicited after negative facial stimuli could be modulated by the decline related to pathological cognitive aging and can contribute in distinguishing HC from SCI, MCI, and AD. Show more

Keywords: Alzheimer’s disease, emotions, event related potentials, HD-EEG, mild cognitive impairment, N170, sLORETA, subjective cognitive impairment

DOI: 10.3233/JAD-180223

Citation: Journal of Alzheimer's Disease, vol. 65, no. 2, pp. 543-575, 2018

Authors: de la Rubia Ortí, José Enrique | García-Pardo, María Pilar | Drehmer, Eraci | Sancho Cantus, David | Julián Rochina, Mariano | Aguilar, Maria Asunción | Hu Yang, Iván

Article Type: Research Article

Abstract: Background: Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder (mainly in women), and new therapies are needed. In this way, ketone bodies are a direct source of cellular energy and can be obtained from coconut oil, postulating that coconut oil could be a new non-pharmacological alternative in AD patients. Objective: The aim of this study is to detect changes in the main cognitive functions of patients with AD after following a coconut oil enriched Mediterranean diet, and to determine whether there are differences in function of stage or sex. Methods: A prospective, longitudinal, qualitative, analytic, …experimental study was carried out in 44 patients with AD, who were randomly divided into two homogenous groups of 22 patients each: an experimental group of patients who followed a coconut oil enriched Mediterranean diet for 21 days and a control group. In order to determine the cognitive changes after the intervention, we carried out the 7 Minute Screen, which analyses temporal orientation, visuospatial and visuoconstructive abilities, and semantic and episodic memory. Results: After intervention with coconut oil, improvements in episodic, temporal orientation, and semantic memory were observed, and it seems that the positive effect is more evident in women with mild-moderate state, although other improvements in males and severe state were also shown. Conclusions: The isocaloric coconut oil enriched Mediterranean diet seems to improve cognitive functions in patients with AD, with differences according to patient sex and degree of severity of the disease, although more studies in this line are needed. Show more

Keywords: Alzheimer’s disease, coconut oil, cognitive functions, ketone bodies, Mediterranean diet

DOI: 10.3233/JAD-180184

Citation: Journal of Alzheimer's Disease, vol. 65, no. 2, pp. 577-587, 2018

Authors: Tan, Edwin C.K. | Eriksdotter, Maria | Garcia-Ptacek, Sara | Fastbom, Johan | Johnell, Kristina

Article Type: Research Article

Abstract: Background: Anticholinergic burden is associated with poorer cognitive and functional outcomes in people with dementia. However, the impact of anticholinergics on significant adverse outcomes such as stroke has not been studied previously. Objective: To investigate the association between total anticholinergic cognitive burden (ACB) and risk of stroke and death in people with different dementia subtypes. Methods: This was a cohort study of 39,107 people with dementia and no prior history of stroke registered in the Swedish Dementia Registry (SveDem) from 2008–2014. Data were extracted from the Swedish Prescribed Drug Register, the Swedish National Patient Register, and …the Swedish Total Population Register. Competing risk regression models were used to compute hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between time-varying ACB score and risk of stroke and all-cause mortality. Results: During a mean follow-up period of 2.31 (standard deviation 1.66) years, 11,224 (28.7%) individuals had a stroke or died. Compared with non-users of anticholinergic medications, ACB score of 1 (HR 1.09, 95% CI 1.04–1.14) and ACB score of ≥2 (HR 1.20, 95% CI 1.14–1.26) increased the risk of developing the composite outcome of stroke and death. When stratifying by dementia disorder, the association remained significant in Alzheimer’s disease, mixed dementia, and vascular dementia. Conclusions: The use of anticholinergic medicines may be associated with an increased risk of stroke and death in people with dementia. A dose-response relationship was observed. Careful consideration should be made when prescribing medications with anticholinergic properties to people with dementia. Show more

Keywords: Alzheimer’s disease, anticholinergics, cohort studies, dementia, registries, stroke, vascular dementia

DOI: 10.3233/JAD-180353

Citation: Journal of Alzheimer's Disease, vol. 65, no. 2, pp. 589-596, 2018

Authors: Kim, Yeshin | Jang, Hyemin | Kim, Seung Joo | Cho, Soo Hyun | Kim, Si Eun | Kim, Sung Tae | Kim, Hee Jin | Moon, Seung Hwan | Ewers, Michael | Im, Kiho | Kwon, Hunki | Na, Duk L. | Seo, Sang Won

Article Type: Research Article

Abstract: Late life depression is related to pathologic burdens, such as cerebral small vascular disease (CSVD) and amyloid, which are associated with brain network changes and cortical thinning. To examine the associations of various CSVD imaging markers, amyloid, and network changes with depression in cognitively impaired patients, we prospectively recruited 228 cognitively impaired patients having various degrees of amyloid and CSVD who underwent diffuse tensor image and PiB PET. Greater CSVD burden was associated with greater Geriatric Depression Scale (GDS) (white matter hyperintensities, WMH: p  = 0.025, lacunes: p  < 0.001) but not with amyloid (p  = 0.095), and cortical thinning (p  = 0.630) was …not associated with greater GDS. The changes in white matter networks were related to GDS with decreasing integration (global efficiency: p  < 0.001) and increasing segregation (clustering coefficient: p  = 0.009). The network changes mediated the relationships of WMH and lacunes with GDS. Our findings provide insight to better understand how CSVD burdens contribute to depression in cognitively impaired patients having varying degrees of amyloid and vascular burdens. Show more

Keywords: Depression, network, small vessel disease

DOI: 10.3233/JAD-180394

Citation: Journal of Alzheimer's Disease, vol. 65, no. 2, pp. 597-605, 2018

Authors: Gray, Shelly L. | Anderson, Melissa L. | Hanlon, Joseph T. | Dublin, Sascha | Walker, Rod L. | Hubbard, Rebecca A. | Yu, Onchee | Montine, Thomas J. | Crane, Paul K. | Sonnen, Josh A. | Keene, C. Dirk | Larson, Eric B.

Article Type: Research Article

Abstract: Background: Anticholinergic medication exposure has been associated with increased risk for dementia. No study has examined the association between anticholinergic medication use and neuropathologic lesions in a community-based sample. Objective: To examine the relationship between anticholinergic exposure and dementia-related neuropathologic changes. Methods: Within a community-based autopsy cohort (N = 420), we ascertained use of anticholinergic medications over a 10-year period from automated pharmacy data and calculated total standardized daily doses (TSDD). We used modified Poisson regression to calculate adjusted relative risks (RRs) and 95% confidence intervals (CIs) for the association between anticholinergic exposure and dementia-associated neuropathology. Inverse probability …weighting was used to account for selection into the autopsy cohort. Results: Heavy anticholinergic exposure (≥1,096 TSDD) was not associated with greater neuropathologic changes of Alzheimer’s disease; the adjusted RRs for heavy use of anticholinergics (≥1,096 TSDD) compared to no use were 1.22 (95% CI 0.81–1.88) for neuritic plaque scores and 0.89 (0.47–1.66) for extent of neurofibrillary degeneration. Moderate (91–1,095 TSDD) and heavy use of anticholinergics was associated with a significantly lower cerebral microinfarct burden compared with no use with adjusted RRs of 0.44 (0.21–0.89) and 0.24 (0.09–0.62), respectively. Anticholinergic exposure was not associated with macroscopic infarcts or atherosclerosis. Conclusions: Use of anticholinergic medications is not associated with Alzheimer’s disease-related neuropathologic changes but is associated with lower cerebral microinfarct burden. Further research into biological mechanisms underlying the anticholinergic-dementia link is warranteds. Show more

Keywords: Alzheimer’s disease, cholinergic antagonists, neuritic plaques, neurofibrillary tangles, neuropathology

DOI: 10.3233/JAD-171174

Citation: Journal of Alzheimer's Disease, vol. 65, no. 2, pp. 607-616, 2018

Authors: Kontaxopoulou, Dionysia | Beratis, Ion N. | Fragkiadaki, Stella | Pavlou, Dimosthenis | Andronas, Nikos | Yannis, George | Economou, Alexandra | Papanicolaou, Andrew C. | Papageorgiou, Sokratis G.

Article Type: Research Article

Abstract: Incidental memory can be defined as the ability to acquire information unintentionally. The present study investigated incidental memory performance in amnestic mild cognitive impairment (aMCI) and mild Alzheimer’s disease (AD) patients; additionally, hippocampal atrophy between groupswas examined. Twenty-nine aMCI patients (14 with hippocampal atrophy, measured by the Medial Temporal Lobe Atrophy scale), 15 mild AD patients, and 20 cognitively intact individuals underwent a detailed medical and neuropsychological assessment examining intentional memory, using the Hopkins Verbal Learning Test-Revised and the Brief Visuospatial Memory Test. Participants first took part in a driving simulator experiment, followed by an unexpected incidental memory questionnaire referring …to elements related to the driving simulation. The mild AD group performed worse than the aMCI group and the control group both in incidental and intentional memory tasks, whereas the aMCI group differed significantly from the control group only in the intentional memory tasks. The incidental recognition memory task was the only measure that differed between aMCI patients with and without hippocampal atrophy. Moreover, incidental memory tasks were the only measures that correlated significantly with both left and right hippocampal atrophy. The current findings indicate that incidental memory testing may provide potentially useful information for detecting aMCI patients with greater hippocampal atrophy, who may be considered at higher risk of developing dementia due to AD. Show more

Keywords: Alzheimer’s disease, atrophy of hippocampus, driving simulator experiment, incidental memory, intentional memory, mild cognitive impairment

DOI: 10.3233/JAD-180328

Citation: Journal of Alzheimer's Disease, vol. 65, no. 2, pp. 617-627, 2018

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