Journal of Alzheimer's Disease - Volume 57, issue 1

Authors: Amen, Daniel G. | Krishnamani, Pavitra | Meysami, Somayeh | Newberg, Andrew | Raji, Cyrus A.

Article Type: Research Article

Abstract: Background: Depression and cognitive disorders (CDs) are two common co-morbid afflictions that commonly present with overlapping symptoms. Objective: To evaluate if perfusion neuroimaging with brain SPECT can distinguish persons with depression from those with CDs or both conditions. Methods: Inclusion criteria were DSM-IV defined depression or CDs (Alzheimer’s disease, vascular dementia, dementia not otherwise specified, and amnestic disorders not otherwise specified) including persons with both (total n  = 4,541; 847 CDs, 3,269 depression, 425 with both). Perfusion differences between the groups were calculated using two-sampled t -tests corrected for multiple comparisons. Diagnostic separation was determined with …discriminant analysis. Feature selection revealed predictive regions in delineating depression from CDs and comorbid cases. Results: Persons with CDs had lower cerebral perfusion compared to depression. In co-morbid persons, cerebral hypoperfusion was additive, with regions showing lower regional cerebral blood flow compared to either diagnosis alone. Both baseline and concentration SPECT regions yielded correct classification of 86% and leave one out cross-validation of 83%. AUC analysis for SPECT regions showed 86% accuracy, 80% sensitivity and 75% specificity. Discriminant analysis separated depression and CDs from comorbid cases with correct classification of 90.8% and cross validated accuracy of 88.6%. Area under the curve was 83% with sensitivity of 80% and specificity of 70%. Feature selection identified the most predictive regions in left hippocampus, right insula, cerebellar, and frontal lobe regions. Conclusion: Quantitative perfusion SPECT neuroimaging distinguishes depression from dementia and those with both co-morbidities. Perfusion brain SPECT can be utilized clinically to delineate between these two disorders. Show more

Keywords: Dementia, depression, neuroimaging, SPECT

DOI: 10.3233/JAD-161232

Citation: Journal of Alzheimer's Disease, vol. 57, no. 1, pp. 253-266, 2017

Authors: Nakayama, Sachiko | Suda, Akimitsu | Nakanishi, Atsushi | Motoi, Yumiko | Hattori, Nobutaka

Article Type: Research Article

Abstract: Behavioral and psychological symptoms of dementia (BPSD) occur in up to 80% of AD patients and represent one of the largest factors contributing to caregiver burden. To analyze the effect of galantamine on BPSD and caregiver burden, we treated a total of 50 patients with mild AD for 12 weeks and evaluated them using the Neuropsychiatric Inventory (NPI) and Japanese version of the Zarit Caregiver Burden Interview (ZBI). We also performed regional cerebral blood flow single photon emission computed tomography (rCBF SPECT) at baseline using three-dimensional sterotatic surface projections. Total NPI and ZBI scores did not significantly change after 12-week …galantamine treatment. To identify the characteristics of patients who showed improvement after galantamine treatment, we divided patients into two groups, those with and those without sub-items on the NPI. Patients with aggression showed improvement in ZBI scores (p  < 0.05). A comparison of rCBF SPECT between these two groups indicated that patients with aggression exhibited increased rCBF in the right prefrontal cortex compared with those without aggression. In a patient with aggression, 20-month treatment with galantamine inhibited increases in the rCBF area in the right prefrontal lobe. These results suggest that galantamine response may be related to aggression and dysfunction of the prefrontal cortex. Show more

Keywords: Alzheimer’s disease, agitation, galantamine, prefrontal cortex

DOI: 10.3233/JAD-160902

Citation: Journal of Alzheimer's Disease, vol. 57, no. 1, pp. 267-273, 2017

Authors: Marioni, Riccardo E. | Campbell, Archie | Hagenaars, Saskia P. | Nagy, Reka | Amador, Carmen | Hayward, Caroline | Porteous, David J. | Visscher, Peter M. | Deary, Ian J.

Article Type: Research Article

Abstract: Stratification by genetic risk factors for Alzheimer’s disease (AD) may help identify groups with the greatest disease risk. Biological changes that cause late-onset AD are likely to occur years, if not decades prior to diagnosis. Here, we select a subset of the Generation Scotland: Scottish Family Health Study cohort in a likely preclinical age-range of 60–70 years (subset n  = 3,495 with cognitive and genetic data). We test for cognitive differences by polygenic risk scores for AD. The polygenic scores are constructed using all available SNPs, excluding those within a 500 kb distance of the APOE locus. Additive and multiplicative effects …of APOE status on these associations are investigated. Small memory decrements were observed in those with high polygenic risk scores for AD (standardized beta –0.04, p  = 0.020). These associations were independent of APOE status. There was no difference in AD polygenic scores across APOE haplotypes (p  = 0.72). Individuals with high compared to low polygenic risk scores for AD (top and bottom 5% of the distribution) show cognitive decrements, albeit much smaller than for APOE ɛ 4ɛ 4 compared to ɛ 3ɛ 3 individuals (2.3 versus 3.5 fewer points on the processing speed test, and 1.8 versus 2.8 fewer points on the memory test). Polygenic risk scores for AD may help identify older individuals at greatest risk of cognitive decline and preclinical AD. Show more

Keywords: Alzheimer’s disease, apolipoprotein E, cognitive function, genetics, polygenic traits

DOI: 10.3233/JAD-161070

Citation: Journal of Alzheimer's Disease, vol. 57, no. 1, pp. 275-283, 2017

Authors: El Haj, Mohamad | Gallouj, Karim | Antoine, Pascal

Article Type: Research Article

Abstract: We investigated whether an external memory aid (i.e., Google Calendar) would alleviate prospective memory compromise in a patient with mild Alzheimer’s disease. The patient was asked in the baseline phase to perform three prospective targeted events (e.g., attending her weekly bridge game at the community club) and three prospective control events (e.g., buying her weekly magazine). The same six prospective events were assessed in the intervention phase but the targeted-events were cued by Google Calendar while the control-events were not. Results showed less omission of the targeted events in the training phase than in the baseline phase, suggesting a positive …effect of Google Calendar. This case report offers a unique view into how smartphone calendars may alleviate prospective memory compromise in patients with mild Alzheimer’s disease. Show more

Keywords: Alzheimer’s disease, Google Calendar, prospective memory: rehabilitation, smartphones

DOI: 10.3233/JAD-161283

Citation: Journal of Alzheimer's Disease, vol. 57, no. 1, pp. 285-291, 2017

Authors: Lindemer, Emily R. | Greve, Douglas N. | Fischl, Bruce | Augustinack, Jean C. | Salat, David H. | for the Alzheimer’s Disease Neuroimaging Initiative

Article Type: Research Article

Abstract: Background: White matter signal abnormalities (WMSA) (also known as ‘hyperintensities’) on MRI are commonly seen in normal aging and increases have been noted in Alzheimer’s disease (AD), but whether there is a spatial specificity to these increases is unknown. Objective: To discern whether or not there is a spatial pattern of WMSA in the brains of individuals with AD that differs from those who exhibit cognitively healthy aging. Method: Structural MRI data from the Alzheimer’s Disease Neuroimaging Initiative public database were used to quantify WMSA in 35 regions of interest (ROIs). Regional measures were compared …between cognitively healthy older controls (OC; n  = 107) and individuals with a clinical diagnosis of AD (n  = 127). Regional WMSA volume was also assessed in individuals with mild cognitive impairment (MCI; n  = 74) who were 6, 12, and 24 months away from AD conversion. Results: WMSA volume was significantly greater in AD compared to OC in 24 out of 35 ROIs after controlling for age, and nine were significantly higher after normalizing for total WMSA. Regions with greater WMSA volume in AD included rostral frontal, inferior temporal, and inferior parietal WM. In MCI, frontal and temporal regions demonstrated significantly greater WMSA volume with decreasing time-to-AD-conversion. Discussion: Individuals with AD have greater regional volume of WMSA compared to OC regardless of age or total WMSA volume. Accumulation of regional WMSA is linked to time to AD conversion in individuals with MCI. These findings indicate WMSA is an important pathological component of AD development. Show more

Keywords: Aging, Alzheimer’s disease, cerebrovascular, hyperintensities, magnetic resonance imaging, mild cognitive impairment, white matter

DOI: 10.3233/JAD-161057

Citation: Journal of Alzheimer's Disease, vol. 57, no. 1, pp. 293-303, 2017

Authors: Zhu, Carolyn W. | Cosentino, Stephanie | Ornstein, Katherine A. | Gu, Yian | Andrews, Howard | Stern, Yaakov

Article Type: Research Article

Abstract: Background: Few studies have examined how dementia and comorbidities may interact to affect healthcare expenditures. Objective: To examine whether effects of dementia severity on Medicare expenditures differed for individuals with different levels of comorbidities. Methods: Data are drawn from the Washington Heights-Inwood Columbia Aging Project (WHICAP). Comprehensive clinical assessments of dementia severity were systematically carried out at ∼18 month intervals. Dementia severity was measured by Clinical Dementia Rating (CDR). Comorbidities were measured by a modified Elixhauser comorbidities index. Generalized linear models examined effects of dementia severity, comorbidities, and their interactions on Medicare expenditures (1999–2010). …Results: At baseline, 1,280 subjects were dementia free (CDR = 0, 66.4%), 490 had very mild dementia (CDR = 0.5, 25.4%), 108 had mild dementia (CDR = 1, 5.6%), and 49 had moderate/severe dementia (CDR = 2/3, 2.5%). Average annual Medicare expenditures for individuals with moderate/severe dementia were more than twice as high as those who were dementia free (CDR = 0: $9,108, CDR = 0.5/1: $11,664, CDR≥2: $19,604, p  < 0.01). Expenditures were approximately 10 times higher among those with≥3 comorbidities than among those with no comorbidities ($2,612 for those with no comorbidities, to $6,109 for those with 1, $10,656 for those with 2, and $30,244 for those with≥3 comorbidities, p  < 0.001). Dementia severity was associated with higher expenditures, but comorbidities were the most important predictor of expenditures. We did not find strong interaction effects between number of comorbidities and dementia severity. Conclusions: Increasing dementia severity and higher comorbidities are associated with higher Medicare expenditures. Care of individuals with dementia should focus on management of comorbidities. Show more

Keywords: Health expenditure, Medicare, economics, comorbidities, longitudinal analysis

DOI: 10.3233/JAD-161077

Citation: Journal of Alzheimer's Disease, vol. 57, no. 1, pp. 305-315, 2017