Dementia and Geriatric Cognitive Disorders

doi: 10.1159/000346601pmid: N/A

Cacciatore, Francesco; Testa, Gianluca; Langellotto, Assunta; Galizia, Gianluigi; Della-Morte, David; Gargiulo, Gaetano; Bevilacqua, Agnese; Del Genio, Maria Teresa; Canonico, Vincenzo; Rengo, Franco; Abete, Pasquale

doi: 10.1159/000342195pmid: 22986752

Background: The role of ventricular rate response (VRr) on the incidence of dementia in elderly subjects with cognitive impairment and atrial fibrillation (AF) is not known. Thus, we examined the ability of VRr to predict dementia in cognitively impaired elderly subjects with and without AF. Methods: A total of 358 cognitively impaired elderly subjects (MMSE <24) with and without AF were stratified in low/high (<50/>90) and moderate (>50/<90 bpm) VRr. A 10-year follow-up was performed. Results: Cognitively impaired subjects with dementia at the end of the follow-up were 135 (37.7%): 33 in the presence (75.0%) and 102 (32.5%) in the absence of AF (p < 0.001). Multivariate analysis shows that AF is a strong predictor of dementia (hazard ratio, HR = 4.10; 95% confidence interval, CI = 1.80–9.30, p < 0.001). More importantly, low/high VRr (<50/>90 bpm) is predictive of dementia in the presence (HR = 7.70, 95% CI = 1.10–14.20, p = 0.03) but not in the absence (HR = 1.85; 95% CI = 0.78–4.47; p = 0.152) of AF. Conclusions: This study demonstrates that AF predicts dementia in elderly subjects with cognitive impairment. Moreover, VRr seems to play a key role in the incidence of dementia in cognitively impaired elderly subjects with AF.

Pedro, Tatiane; Weiler, Marina; Yasuda, Clarissa L.; D’Abreu, Anelyssa; Damasceno, Benito P.; Cendes, Fernando; Balthazar, Marcio L.F.

doi: 10.1159/000342118pmid: 22986782

Background: It is widely known that atrophy of medial temporal structures is present in the mild stage of Alzheimer’s disease (AD) and amnestic mild cognitive impairment (aMCI). However, structures such as the thalamus and corpus callosum are much less studied. Methods: We compared the volumes of the entorhinal cortex, hippocampus, thalamus and the corpus callosum in 14 controls, 14 patients with mild AD and 15 with aMCI and correlated these volumes with neuropsychological data. MRI was obtained at 2 T followed by manual segmentation. Results: We found atrophy in hippocampi and thalami of MCI patients compared to controls, and in the bilateral entorhinal cortex of aMCI compared to AD patients. All the structures showed atrophy in AD patients compared to controls, including the corpus callosum. Conclusions: Our study confirms that thalamic areas are atrophied in aMCI, and the corpus callosum might represent a good structural marker for mild AD. Those areas were associated with cognitive functions already described in the literature.

Ye, Byoung Seok; Seo, Sang Won; Lee, Yunhwan; Kim, Seong Yoon; Choi, Seong Hye; Lee, Young Min; Kim, Do Hoon; Han, Hyun Jeong; Na, Duk L.; Kim, Eun-Joo

doi: 10.1159/000342973pmid: 23037957

Background: Amnestic mild cognitive impairment (aMCI) is regarded as a prodromal stage of Alzheimer’s disease (AD). Given that patients with early-onset AD (EOAD) and with late-onset AD (LOAD) are known to have different clinical courses, symptoms and neuroimaging findings, early-onset (EOMCI) and late-onset aMCI (LOMCI) might be expected to have similar differences as EOAD versus LOAD. Methods: Our study involving 425 patients with aMCI (124 EOMCI, 301 LOMCI), who were followed for around 1.5 years, and 958 normal control subjects (NC) investigated neuropsychological characteristics and prediction of progression to AD in patients with EOMCI versus LOMCI. Neuropsychological scores were compared between EOMCI, LOMCI and NC with analyses of covariance controlling age, gender, education and disease duration. The risk of AD conversion was evaluated by Cox proportional hazard analyses. Results: The baseline neuropsychological performances were comparable between EOMCI and LOMCI. Visuospatial memory for EOMCI and verbal memory scores for LOMCI were significant predictors of AD conversion. Conclusion: Our study indicates that EOMCI with visuospatial memory impairment, which implies underlying right predominant pathology, and LOMCI with poor verbal memory, which suggests underlying left predominant pathology, are individual conditions at an increased risk of conversion to AD.

Han, Hyun Jeong; Kim, Byeong C.; Lee, Jun-Young; Ryu, Seung-Ho; Na, Hae Ri; Yoon, Soo Jin; Park, Hyun Young; Shin, Joon Hyun; Cho, Soo-Jin; Yi, Hyon-Ah; Choi, Mun Seong; Heo, Jae-Hyeok; Park, Kyung Won; Kim, Kwang K.; Choi, Seong Hye

Xue, Shouru; Cai, Xiuyin; Li, Wanjun; Zhang, Zhengchun; Dong, Wanli; Hui, Guozhen

doi: 10.1159/000343491pmid: 23075931

Background/Aims: Endothelial microparticles (EMPs) in plasma are elevated in several vascular diseases. Alzheimer’s disease (AD) is associated with microcirculatory injury, capillary blocking and disruption of the blood-brain barrier. We wanted to test the hypothesis that EMPs would be increased in AD patients and would correlate with a cognitive decline, and to determine if EMPs are released as a result of activation or apoptosis/necrosis in AD. Methods: EMP levels in plasma of AD patients and controls were quantified by flow cytometry. EMP markers for apoptosis/necrosis [platelet/endothelial cell adhesion molecule-1 (PECAM-1)/CD31] and for activation (E-selectin/CD62e) were evaluated. The EMP CD62E/CD31 populations ratio of ≤1.0 was used to differentiate activation from apoptosis. Results: Significantly higher CD31+/CD42– and CD62e+/CD42– counts were observed in the AD group relative to the controls (p < 0.05). There was no difference between the moderate- to-severe AD group and the mild AD group. Significant correlations were found between circulating EMP counts and Mini-Mental State Examination and AD Assessment cognition (ADAS-cog) score. Multivariate regression analysis demonstrated the persistence of significant correlations between ADAS-cog score and CD31+/CD42– EMPs. Conclusion: The (PECAM-1)/CD31 ratio demonstrated that EMPs were generated via apoptosis/necrosis and not by activation. Certain circulating EMP phenotypes may be associated with a cognitive decline of AD patients. EMP analysis shows a promising contribution to understanding vascular pathophysiology in AD.

Taylor, Morag E.; Lord, Stephen R.; Delbaere, Kim; Mikolaizak, A. Stefanie; Close, Jacqueline C.T.

doi: 10.1159/000343077pmid: 23076047

Background/Aims: Cognitively impaired older people are at twice the risk of falls compared to cognitively intact, with approximately 60% falling once or more per year. This study aimed to investigate sensorimotor and balance risk factors for falls in cognitively impaired older people. Methods: 177 community-dwelling older people with mild to moderate cognitive impairment (Mini-Mental State Examination < 24, Addenbrooke’s Cognitive Examination-Revised < 83) were assessed using the Physiological Profile Assessment (PPA). Falls were recorded prospectively for 12 months using monthly calendars with the assistance of carers. Results: Seventy-one participants (43%) fell ≥2 times in the follow-up period. Impaired simple reaction time, postural sway, leaning balance and increased PPA fall risk score were significantly associated with multiple falls. The area under the receiver-operating characteristic curve for the PPA model including tests of vision, proprioception, knee extension strength, reaction time, postural sway and leaning balance was 0.75 (95% confidence interval: 0.68–0.83). Conclusion: These findings indicate poor performance on physiological fall risk factors, particularly balance, increases the risk of falls in older cognitively impaired people.

Kobayashi, Nobuyuki; Nagata, Tomoyuki; Shinagawa, Shunichiro; Nakayama, Ritsuko; Kondo, Kazuhiro; Nakayama, Kazuhiko; Yamada, Hisashi

doi: 10.1159/000343075pmid: 23075484

Background: We investigated whether neurotrophin (NT)-3 polymorphisms influenced the executive function of patients with 2 separate disease stages with similar dementia conditions: amnestic mild cognitive impairment (A-MCI) or mild Alzheimer disease (AD). Methods: Among 215 outpatients with dementia and MCI, 155 with mild AD (n = 108) or A-MCI (n = 47) were recruited and divided into three genotypic groups based on the representative NT-3 functional polymorphisms rs6332 and rs6489630. Next, we compared the frontal assessment battery (FAB) total and subtest scores between the three genotypic groups. Results: The total FAB score was not significantly associated with the rs6332 and rs6489630 genotypes; however, the conflicting instructions score among the 6 subtests was significantly associated with the rs6332 genotype (p < 0.05). Moreover, in patients with mild AD, the conflicting instructions score differed significantly among the three genotypic groups of rs6332 (p < 0.05) (G/G < A/A: p = 0.042 and G/A < A/A: p = 0.041). No significant differences in any other demographic variables were observed among the three genotypes of rs6332 and rs6489630. Conclusion: These results suggested that an NT-3 polymorphism, rs6332, may significantly influence executive function, reflecting interference performances among patients with mild-stage AD.

Helvik, Anne-Sofie; Selbæk, Geir; Engedal, Knut

doi: 10.1159/000343932pmid: 23128048

Background/Aims: We studied cognitive functioning 1 year after hospitalization (T2) in patients at least 65 years old without cognitive impairment at baseline (T1). Methods: Cognition was assessed using the Mini-Mental State Examination (MMSE) at both time points. We included 211 (114 women) patients with a mean age of 78.3 (SD 7.0) years and an MMSE score of 24 and above. Results: At T2, 69 (32.7%) patients had an MMSE score below 24. In participants with MMSE 24–26 at T1, cognitive decline was related to impaired physical self-maintenance, a decline in the performance of the instrumental activities of daily living, impaired hearing and less reading ability. In participants with MMSE 27–30, cognitive decline was associated with higher comorbidity (Charlson Index) and impaired physical self-maintenance and hearing. Conclusion: A reduced functioning level and increased comorbidity predicted a decline in cognitive functioning.

Ryan, Kelly A.; Weldon, Anne; Persad, Carol; Heidebrink, Judith L.; Barbas, Nancy; Giordani, Bruno

doi: 10.1159/000339955pmid: 23128102

Background: Caregivers of patients with mild cognitive impairment (MCI) need similar levels of support services as Alzheimer’s disease (AD) caregivers, but it is unclear if this translates to increased caregiver burden. Methods: 135 participants and their caregivers (40 MCI, 55 AD and 40 normal controls, NC) completed questionnaires, and the patients were administered neuropsychological tests. Results: The MCI caregivers reported significantly more overall caregiving burden than the NC, but less than the AD. They showed similar levels of emotional, physical and social burden as the AD caregivers. Among the MCI caregivers, the neuropsychiatric symptoms and executive functioning of the patients were related to a greater burden, and the caregivers with a greater burden reported lower life satisfaction and social support, and a greater need for support services. Conclusion: These results indicate that MCI caregivers are at increased risk for caregiver stress, and they require enhanced assistance and/or education in caring for their loved ones.