[Show abstract][Hide abstract] ABSTRACT: Dementia with Lewy bodies (DLB) is characterized by preserved whole brain and medial temporal lobe volumes compared with Alzheimer's disease dementia (AD) on magnetic resonance imaging. However, frequently coexistent AD-type pathology may influence the pattern of regional brain atrophy rates in DLB patients. We investigated the pattern and magnitude of the atrophy rates from 2 serial MRIs in autopsy-confirmed DLB patients (n = 20) and mixed DLB/AD patients (n = 22), compared with AD (n = 30) and elderly nondemented control subjects (n = 15), followed antemortem. DLB patients without significant AD-type pathology were characterized by lower global and regional rates of atrophy, similar to control subjects. The mixed DLB/AD patients displayed greater atrophy rates in the whole brain, temporoparietal cortices, hippocampus and amygdala, and ventricle expansion, similar to AD patients. In the DLB and DLB/AD patients, the atrophy rates correlated with Braak neurofibrillary tangle stage, cognitive decline, and progression of motor symptoms. Global and regional atrophy rates are associated with AD-type pathology in DLB, and these rates can be used as biomarkers of AD progression in patients with LB pathology.
[Show abstract][Hide abstract] ABSTRACT: Objective: We investigated the association between APOE ε4 status and spatial navigation in patients with amnestic mild cognitive impairment (aMCI) and assessed the role of hippocampal volume in this association. Method: Participants were 74 patients with clinically confirmed aMCI (33 APOE ε4 noncarriers, 26 heterozygous, and 15 homozygous ε4 carriers). Body-centered (egocentric) and world-centered (allocentric) spatial navigation in a computerized human analogue of the Morris Water Maze was assessed. Brain MRI with subsequent automated hippocampal volumetry was included. Results: Groups were similar in neuropsychological profile. Controlling for age, sex, education, and free memory recall, the APOE ε4 carriers performed more poorly on all spatial navigation subtasks (ps < .05). APOE ε4 homozygotes performed worse than heterozygotes (p = .021). Right hippocampal volume accounted for the differences in allocentric and delayed subtasks (ps > .05), but not in the egocentric subtask (p < .001). Conclusions: Using an easy-to-use, computer-based tool to assess spatial navigation, we found spatial navigation deficits to worsen in a dose-dependent manner as a function of APOE ε4 status. This was at least partially due to differences in right hippocampal volume. (PsycINFO Database Record (c) 2014 APA, all rights reserved).
[Show abstract][Hide abstract] ABSTRACT: Background and Objective: Cognitive deficits in older adults attributable to Alzheimer's disease (AD) pathology are featured early on by hippocampal impairment. Among tests used to evaluate memory, verbal memory tests with controlled encoding and cued recall are believed to be specific for hippocampal impairment. The objective of this study was to assess the relation between left and right hippocampal volumes and several frequently used memory tests. Methods: Fifty six nondemented older adults (30 with amnestic mild cognitive impairment and 26 cognitively healthy older adults) underwent neuropsychological testing including: 1) The Enhanced Cued Recall test (ECR), a memory test with controlled encoding and recall; 2) the Auditory Verbal Learning Test (AVLT), a verbal memory test without controlled encoding and with delayed recall; and 3) The Rey-Osterrieth Complex Figure test (ROCF), a visuospatial memory test-recall condition. 1.5T brain MRI scans were used to measure estimated total intracranial volume (eTIV) along with hippocampal right and left volumes, which were measured with quantitative volumetry using FreeSurfer package (version 4.4.0). Spearman partial correlation controlled for age was used to correct for non-normal score distribution and effect of age. Results: We found moderate correlations of hippocampal volumes with AVLT 1-5 scores, AVLT delayed recall, ECR free and total recall, and ROCF reproduction. Total recall in ECR using cued recall was not superior to any of the free recall tests. No correlation in any memory test was achieved with eTIV. Conclusion: Verbal memory tests, either with controlled encoding and cued delayed recall (ECR), or without it (AVLT), as well as nonverbal memory test with delayed recall (ROCF), equally reflect hippocampal atrophy in nondemented older adults.
Journal of Alzheimer's disease: JAD 03/2014; · 4.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The field of aging and dementia is increasingly preoccupied with identification of the asymptomatic phenotype of Alzheimer disease (AD). A quick glance at historical landmarks in the field indicates that the agenda and priorities of the field have evolved over time. The initial focus of research was dementia. In the late 1980s and 1990s, dementia researchers reported that some elderly persons are neither demented nor cognitively normal. Experts coined various terms to describe the gray zone between normal cognitive aging and dementia, including mild cognitive impairment. Advances made in epidemiologic, neuroimaging, and biomarkers research emboldened the field to seriously pursue the avenue of identifying asymptomatic AD. Accurate "diagnosis" of the phenotype has also evolved over time. For example, the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM-5) Task Force is contemplating to use the terms major and minor neurocognitive disorders. The six papers published in this edition of the journal pertain to mild cognitive impairment, which is envisaged to become a subset of minor neurocognitive disorders. These six studies have three points in common: 1) All of them are observational studies; 2) they have generated useful hypotheses or made important observations without necessarily relying on expensive biomarkers; and 3) Based on the new National Institute on Aging and the Alzheimer's Association guidelines, all the studies addressed the symptomatic phase of AD. Questionnaire-based observational studies will continue to be useful until such a time that validated biomarkers, be it chemical or neuroimaging, become widely available and reasonably affordable.
The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry 08/2012; 20(10):821-6. · 3.35 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cognitive deficits in older adults attributable to Alzheimer's disease (AD) pathology are featured early on by hippocampal impairment. Among these individuals, deterioration in spatial navigation, manifested by poor hippocampus-dependent allocentric navigation, may occur well before the clinical onset of dementia. Our aim was to determine whether allocentric spatial navigation impairment would be proportional to right hippocampal volume loss irrespective of general brain atrophy. We also contrasted the respective spatial navigation scores of the real-space human Morris water maze with its corresponding 2D computer version. We included 42 cognitively impaired patients with either amnestic mild cognitive impairment (n = 23) or mild and moderate AD (n = 19), and 14 cognitively intact older controls. All participants underwent 1.5T MRI brain scanning with subsequent automatic measurement of the total brain and hippocampal (right and left) volumes. Allocentric spatial navigation was tested in the real-space version of the human Morris water maze and in its corresponding computer version. Participants used two navigational cues to locate an invisible goal independent of the start position. We found that smaller right hippocampal volume was associated with poorer navigation performance in both the real-space (β = -0.62, P < 0.001) and virtual (β = -0.43, P = 0.026) versions, controlling for demographic variables, total brain and left hippocampal volumes. In subsequent analyses, the results were significant in cognitively impaired (P ≤ 0.05) but not in cognitively healthy (P > 0.59) subjects. The respective real-space and virtual scores strongly correlated with each other. Our findings indicate that the right hippocampus plays a critical role in allocentric navigation, particularly when cognitive impairment is present.
Proceedings of the National Academy of Sciences 02/2012; 109(7):2590-4. · 9.81 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Spatial navigation is a skill of determining and maintaining a trajectory from one place to another. Mild progressive decline of spatial navigation develops gradually during the course of physiological ageing. Nevertheless, severe spatial navigation deficit can be the first sign of incipient Alzheimer's disease (AD), occurring in the stage of mild cognitive impairment (MCI), preceding the development of a full blown dementia. Patients with amnestic MCI, especially those with the hippocampal type of amnestic syndrome, are at very high risk of AD. These patients present with the same pattern of spatial navigation impairment as do the patients with mild AD. Spatial navigation testing of elderly as well as computer tests developed for routine clinical use thus represents a possibility for further investigation of this cognitive domain, but most of all, an opportunity for making early diagnosis of AD.
Frontiers in Aging Neuroscience 01/2012; 4:16. · 5.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Spatial navigation performance in the Hidden Goal Task (HGT), a real-space human analogue of the Morris Water Maze, can identify amnestic mild cognitive impairment (aMCI) patients with memory impairment of the hippocampal type, a known indicator of incipient Alzheimer's disease (AD).
Contrast results from computer versus real-space versions of the HGT.
A total of 42 aMCI patients were clinically and neuropsychologically classified into: (1) memory impairment of the hippocampal type--the hippocampal aMCI (HaMCI; n = 10) and (2) isolated retrieval impairment--the nonhippocampal aMCI (NHaMCI; n = 32). Results were compared to the control (n = 28) and AD (n = 21) groups.
The HaMCI group, although similar to the NHaMCI group with respect to overall cognitive impairment, performed poorer on the computer version of the HGT and yielded parallel results to the real-space version. The two versions were strongly correlated.
Both versions of the HGT can reliably identify aMCI with pronounced memory impairment of the hippocampal type. The computer version of the HGT may be a useful, relatively inexpensive screening tool for early detection of individuals at a high risk of AD.