Journal of Alzheimer's Disease - Volume 62, issue 4

Authors: Sugarman, Michael A. | Alosco, Michael L. | Tripodis, Yorghos | Steinberg, Eric G. | Stern, Robert A.

Article Type: Research Article

Abstract: Background: Mild cognitive impairment (MCI) is an intermediate diagnosis between normal cognition (NC) and dementia, including Alzheimer’s disease (AD) dementia. However, MCI is heterogeneous; many individuals subsequently revert to NC while others remain stable at MCI for several years. Identifying factors associated with this diagnostic instability could assist in defining clinical populations and determining cognitive prognoses. Objective: The current study examined whether neuropsychiatric symptoms could partially account for the temporal instability in cognitive diagnoses. Method: The sample included 6,763 participants from the National Alzheimer’s Coordinating Center Uniform Data Set. All participants had NC at baseline, completed …at least two follow-up visits (mean duration: 5.5 years), and had no recent neurological conditions. Generalized linear models estimated by generalized estimating equations examined associations between changes in cognitive diagnoses and symptoms on the Neuropsychiatric Inventory Questionnaire (NPI-Q) and Geriatric Depression Scale (GDS-15). Results: 1,121 participants converted from NC to MCI; 324 reverted back to NC and 242 progressed to AD dementia. Higher symptoms on the GDS-15 and circumscribed symptom domains on the NPI-Q were associated with conversion from NC to MCI and a decreased likelihood of reversion from MCI to NC. Individuals with higher symptoms on NPI-Q Hyperactivity and Mood items were more likely to progress to AD dementia. Discussion: The temporal instability of MCI can be partially explained by neuropsychiatric symptoms. Individuals with higher levels of specific symptoms are more likely to progress to AD dementia and less likely to revert to NC. Identification and treatment of these symptoms might support cognitive functioning in older adults. Show more

Keywords: Alzheimer’s disease, antidepressants, depression, mild cognitive impairment, neuropsychiatric symptoms

DOI: 10.3233/JAD-170527

Citation: Journal of Alzheimer's Disease, vol. 62, no. 4, pp. 1841-1855, 2018

Authors: Teunissen, Charlotte E. | Chiu, Ming-Jang | Yang, Che-Chuan | Yang, Shieh-Yueh | Scheltens, Philip | Zetterberg, Henrik | Blennow, Kaj

Article Type: Research Article

Abstract: The 42 amino acid form of amyloid-β (Aβ42 ) plays a key role in the pathogenesis of Alzheimer’s disease (AD) and is a core biomarker for the diagnosis of AD. Numerous studies have shown that cerebrospinal fluid (CSF) Aβ42 concentrations are decreased in AD, when measured by enzyme-linked immunosorbent assay (ELISA) and other conventional immunoassays. While most studies report no change in plasma Aβ42 , independent studies using the immunomagnetic reduction (IMR) technique report an increase in plasma Aβ42 levels in AD. To confirm the opposite changes of Aβ42 levels in CSF and plasma for AD, we …assayed the levels of Aβ42 in plasma of subjects with known CSF Aβ42 levels. In total 43 controls and 63 AD patients were selected at two sites: the VU University Medical Center (n  = 55) and Sahlgrenska University Hospital (n  = 51). IMR and ELISA were applied to assay Aβ42 in plasma and CSF, respectively. We found a moderately negative correlation between plasma and CSF Aβ42 levels in AD patients (r  = –0.352), and a weakly positive correlation in controls (r  = 0.186). These findings further corroborate that there are opposite changes of Aβ42 levels in CSF and plasma in AD. The possible causes for the negative correlation are discussed by taken assay technologies, Aβ42 transport from brain to peripheral blood, and sample matrix into account. Show more

Keywords: Amyloid-β , cerebrospinal fluid, immunomagnetic reduction, plasma

DOI: 10.3233/JAD-170784

Citation: Journal of Alzheimer's Disease, vol. 62, no. 4, pp. 1857-1863, 2018

Authors: Stuckenschneider, Tim | Askew, Christopher David | Rüdiger, Stefanie | Polidori, Maria Cristina | Abeln, Vera | Vogt, Tobias | Krome, Andreas | Olde Rikkert, Marcel | Lawlor, Brian | Schneider, Stefan | on behalf of the NeuroExercise Study Group

Article Type: Research Article

Abstract: Background: By 2030, about 74 million people will be diagnosed with dementia, and many more will experience subjective (SCI) or mild cognitive impairment (MCI). As physical inactivity has been identified to be a strong modifiable risk factor for dementia, exercise and physical activity (PA) may be important parameters to predict the progression from MCI to dementia, but might also represent disease trajectory modifying strategies for SCI and MCI. Objective: A better understanding of the relationship between activity, fitness, and cognitive function across the spectrum of MCI and SCI would provide an insight into the potential utility of PA …and fitness as early markers, and treatment targets to prevent cognitive decline. Methods: 121 participants were stratified into three groups, late MCI (LMCI), early MCI (EMCI), and SCI based on the Montreal Cognitive Assessment (MoCA). Cognitive function assessments also included the Trail Making Test A+B, and a verbal fluency test. PA levels were evaluated with an interviewer-administered questionnaire (LAPAQ) and an activity monitor. An incremental exercise test was performed to estimate cardiorespiratory fitness and to determine exercise capacity relative to population normative data. Results: ANCOVA revealed that LMCI subjects had the lowest PA levels (LAPAQ, p  = 0.018; activity monitor, p  = 0.041), and the lowest exercise capacity in relation to normative values (p  = 0.041). Moreover, a modest correlation between MoCA and cardiorespiratory fitness (r  = 0.25; p  < 0.05) was found. Conclusion: These findings suggest that during the earliest stages of cognitive impairment PA and exercise capacity might present a marker for the risk of further cognitive decline. This finding warrants further investigation using longitudinal cohort studies. Show more

Keywords: Cardiorespiratory fitness, mild cognitive impairment, Montreal Cognitive Assessment, physical activity, subjective cognitive impairment

DOI: 10.3233/JAD-170996

Citation: Journal of Alzheimer's Disease, vol. 62, no. 4, pp. 1865-1875, 2018

Authors: Skoog, Ingmar | Kern, Silke | Zetterberg, Henrik | Östling, Svante | Börjesson-Hanson, Anne | Guo, Xinxin | Blennow, Kaj

Article Type: Research Article

Abstract: Background: Low cerebrospinal fluid (CSF) levels of Aβ42 may be the earliest manifestation of Alzheimer’s disease (AD). Knowledge on how CSF Aβ interacts with different brain pathologies early in the disease process is limited. We examined how CSF Aβ markers relate to brain atrophy and white matter lesions (WMLs) in octogenarians with and without dementia to explore the earliest pathogenetic pathways of AD in the oldest old. Objective: To study CSF amyloid biomarkers in relation to brain atrophy and WMLs in 85-year-olds with and without dementia. Methods: 53 octogenarians took part in neuropsychiatric examinations and …underwent both a lumbar puncture and a brain CT scan. CSF levels of Aβ42 and Aβ40 were examined in relation to cerebral atrophy and WMLs. Dementia was diagnosed. Results: In 85-year-olds without dementia, lower levels of both CSF Aβ42 and CSF Aβ40 were associated with WMLs. CSF Aβ42 also correlated with measures of central atrophy, but not with cortical atrophy. In participants with dementia, lower CSF levels of Aβ42 were related to frontal, temporal, and parietal cortical atrophy but not to WMLs. Conclusions: Our findings may suggest that there is an interrelationship between Aβ and subcortical WMLs in older persons without dementia. After onset of dementia, low CSF Aβ42 , probably representing amyloid deposition in plaques, is associated with cortical atrophy. WMLs may be an earlier manifestation of Aβ deposition than cortical degeneration. Show more

Keywords: Alzheimer’s disease, amyloid-β, biomarkers, cerebrospinal fluid, computerized tomography, dementia, epidemiological methods, population-based, vascular dementia, white matter lesions

DOI: 10.3233/JAD-170950

Citation: Journal of Alzheimer's Disease, vol. 62, no. 4, pp. 1877-1886, 2018

Authors: Bertoux, Maxime | Flanagan, Emma C. | Hobbs, Matthew | Ruiz-Tagle, Amparo | Delgado, Carolina | Miranda, Marcelo | Ibáñez, Agustín | Slachevsky, Andrea | Hornberger, Michael

Article Type: Research Article

Abstract: Although a growing body of work has shown that behavioral variant frontotemporal dementia (bvFTD) could present with severe amnesia in approximately half of cases, memory assessment is currently the clinical standard to distinguish bvFTD from Alzheimer’s disease (AD). Thus, the concept of “relatively preserved episodic memory” in bvFTD remains the basis of its clinical distinction from AD and a criterion for bvFTD’s diagnosis. This view is supported by the idea that bvFTD is not characterized by genuine amnesia and hippocampal degeneration, by contrast to AD. In this multicenter study, we aimed to investigate the neural correlates of memory performance in …bvFTD as assessed by the Free and Cued Selective Reminding Test (FCSRT). Imaging explorations followed a two-step procedure, first relying on a visual rating of atrophy of 35 bvFTD and 34 AD patients’ MRI, contrasted with 29 controls; and then using voxel-based morphometry (VBM) in a subset of bvFTD patients. Results showed that 43% of bvFTD patients presented with a genuine amnesia. Data-driven analysis on visual rating data showed that, in bvFTD, memory recall & storage performances were significantly predicted by atrophy in rostral prefrontal and hippocampal/perihippocampal regions, similar to mild AD. VBM results in bvFTD (pFWE <0.05) showed similar prefrontal and hippocampal regions in addition to striatal and lateral temporal involvement. Our findings showed the involvement of prefrontal as well as medial/lateral temporal atrophy in memory deficits of bvFTD patients. This contradicts the common view that only frontal deficits explain memory impairment in this disease and plead for an updated view on memory dysfunctions in bvFTD. Show more

Keywords: Alzheimer’s disease, amnesia, behavioral frontotemporal dementia, hippocampus

DOI: 10.3233/JAD-170771

Citation: Journal of Alzheimer's Disease, vol. 62, no. 4, pp. 1887-1900, 2018