Joscelyn Agron

Stability of Different Subtypes of Mild Cognitive Impairment among the Elderly over a 2- to 3-Year Follow-Up Period

Background/Aims: To investigate the longitudinal stability and progression of different subtypes of mild cognitive impairment (MCI) in older adults. Methods: We classified 217 individuals with no cognitive impairment (NCI), amnestic MCI (aMCI) based on a single test (aMCI-1) or multiple tests (aMCI-2+), nonamnestic MCI (naMCI) based on a single test (naMCI-1) or multiple tests (naMCI-2+), or amnestic + nonamnestic MCI (a+naMCI), using their baseline neuropsychological test scores, and performed annual follow-up evaluations for up to 3 years. Results: None of the subjects with aMCI-2+ reverted to normal during follow-up, with 50% of these subjects remaining stable and 50% worsening over time. Similarly, less than 20% of subjects with aMCI-2+ and a+naMCI reverted to NCI during the follow-up period, whereas 50% of aMCI-1 and 37% with naMCI-1 reverted to NCI during this same period. Conclusion: Reversion to NCI occurs much more frequently when the diagnosis of MCI is based on the results of a single neuropsychological test than when it is based on the results of more memory tests. In epidemiological studies and clinical trials the diagnosis of MCI will likely be more stable if impairment on more than one test is required for amnestic and/or nonamnestic domains.

Cognitive profiles in Alzheimer's disease and in mild cognitive impairment of different etiologies.

There has been increasing interest in determining whether amnestic, nonamnestic and multiple-domain subtypes of mild cognitive impairment (MCI) reflect different disease etiologies. In this study, we examined the extent to which cognitive profiles of nondemented patients with MCI diagnosed with prodromal Alzheimer’s disease (AD) differed from those MCI patients diagnosed with vascular disease. We also compared these diagnostic groups to mildly demented patients diagnosed with AD and normal elderly controls. Results indicate that a majority of both MCI-AD and MCI-vascular patients experienced amnestic features and that multiple-domain was the most common presentation. MCI-AD and MCI-vascular groups did not differ on neuropsychological measures tapping memory, language, visuospatial skills/praxis or executive function. Further both MCI groups could be distinguished from dementia patients with regards to performance on measures of memory but not on non-memory measures. Considerable variability was observed in the degree of memory impairment among MCI patients with scores as much as 6 standard deviations below expected mean values. MCI-AD and MCI-vascular patients frequently exhibit both common and overlapping amnestic and nonamnestic features. The implication of these findings for future clinical research is discussed.

Stability of neurocognitive impairment in different subtypes of mild cognitive impairment.

There has been increasing interest in delineating different cognitive subtypes of mild cognitive impairment (MCI). It remains unclear, however, the extent to which neuropsychological impairment associated with amnestic, nonamnestic, and amnestic+ subtypes of MCI remains stable over time. In this study, 70 persons meeting the criteria for MCI and 38 cognitively normal elderly subjects received a baseline neuropsychological evaluation and were reevaluated 1 year later. Our results indicated that 84.6% of the persons initially classified as amnestic, 75% of those classified as nonamnestic, and 80% of the persons classified as MCI+ evidenced stable or more pronounced neuropsychological impairment across the follow-up period. Less than 7% of the amnestic and amnestic+ cases had nonimpaired neuropsychological profiles at their reevaluation at 12 months, and 16.7% of the nonamnestic cases had nonimpaired neuropsychological test profiles at follow-up. Approximately 87% of the cognitively normal subjects at baseline continued to have unimpaired neuropsychological performance at follow-up. These results indicate that the presence of neuropsychological impairment is relatively stable over a 12-month follow-up period among different cognitive subtypes of MCI, although 15–25% of the cases did not exhibit the specific cognitive deficits that characterized their performance at baseline.

Vulnerability to Proactive Semantic Interference and Progression to Dementia among Older Adults with Mild Cognitive Impairment

There is evidence that vulnerability to proactive semantic interference may be an early manifestation of early Alzheimer’s disease and other neurodegenerative disorders. At present, there is a paucity of data regarding the extent to which such deficits relate to the progression of cognitive deficits and to clinically significant endpoints such as dementia. In this study, we followed 76 older adults, initially diagnosed with mild cognitive impairment, for a period of up to 3 years. Twenty-seven of these individuals (35.5%) progressed from mild cognitive impairment to dementia. An examination of baseline neuropsychological performance indicated lower baseline scores for object memory among those progressing to dementia. However, baseline Mini-Mental State Examination scores, delayed memory for passages, delayed visual memory, letter fluency, category fluency, Trails B and Block Design did not differ among study groups. In contrast, the Semantic Interference Test, a measure susceptible to vulnerability to proactive semantic interference showed the greatest baseline differentiation between those who progressed and those who did not progress to dementia. Further, scores on this measure predicted future progression to dementia with high accuracy. Vulnerability to proactive interference may be an early manifestation of an early dementing process and may have utility in predicting future progression to dementia.

Minimal Atrophy of the Entorhinal Cortex and Hippocampus: Progression of Cognitive Impairment

Background: In Alzheimer’s disease, neurodegenerative atrophy progresses from the entorhinal cortex (ERC) to the hippocampus (HP), limbic system and neocortex. The significance of very mild atrophy of the ERC and HP on MRI scans among elderly subjects is unknown. Methods: A validated visual rating system on coronal MRI scans was used to identify no atrophy of the HP or ERC (HP₀; ERC₀), or minimal atrophy of the HP or ERC (HPma; ERCma), among 414 participants. Subjects fell into the following groups: (1) ERC₀/HP₀, (2) ERCma/HP₀, (3) ERC₀/HPma, and (4) ERCma/HPma. HP volume was independently measured using volumetric methods. Results: In comparison to ERC₀/HP₀ subjects, those with ERC₀/HPma had impairment on 1 memory test, ERCma/HP₀ subjects had impairment on 2 memory tests and the Mini Mental State Examination (MMSE), while ERCma/HPma subjects had impairment on 3 memory tests, the MMSE and Clinical Dementia Rating. Progression rates of cognitive and functional impairment were significantly greater among subjects with ERCma. Conclusion: Minimal atrophy of the ERC results in greater impairment than minimal atrophy of the HP, and the combination is additive when measured by cognitive and functional tests. Rates of progression to greater impairment were higher among ERCma subjects.

The utility of age-specific cut-offs for visual rating of medial temporal atrophy in classifying Alzheimer's disease, MCI and cognitively normal elderly subjects

Background: New research criteria for diagnosing Alzheimers disease (AD) in the mild cognitive impairment stage (MCI-AD) incorporate biomarkers to assign a level of certainty to the diagnosis. Structural MRI is widely available but greatly under-utilized for assessing atrophy of structures affected in early AD, such as the hippocampus (HP), because the quantification of HP volumes (HP-v) requires special expertise, and normative values have not been established. Methods: Elderly subjects (n =273) from the Florida ADRC were classified as having no cognitive impairment (cognitively normal, CN), amnestic mild cognitive impairment (aMCI) or AD. Volumes for the hippocampus (HP-v) were measured on structural MRI scans. A validated visual rating system for measuring medial temporal atrophy (VRS-MTA), including hippocampal, entorhinal cortex and perirhinal cortex atrophy was employed. The participants were subdivided into younger (less than or equal to 75 years of age) and older (greater than 75 years of age) subgroups. Results: Volumetric and VRS-MTA measures were equivalent in predicting classification of CN vs. aMCI for older (area under the receiver operator curves [aROC]: 0.652 vs. 0.723) and younger subjects (aROC: 0.764 vs. 0.736). However, for younger AD subjects, aROC values were significantly higher for VRS-MTA measures (0.920) than for volumetric measures (0.847). Relative to HP-v, VRS-MTA score was significantly more correlated to impairment on a range of memory tests and was more associated with progression of aMCI to AD than HP-v. Conclusion: Structural MRI with VRS-MTA assessment can serve as a biomarker for supporting the diagnosis of MCI-AD. Age-adjusted VRS-MTA scores are at least as effective as HP-v for distinguishing aMCI and AD from CN and for predicting progression from aMCI to AD. VRS-MTA is convenient for use in the clinic as well as for clinical trials and can readily be incorporated into a standardized radiological report.

A New Scale for the Evaluation of Proactive and Retroactive Interference in Mild Cognitive Impairment and Early Alzheimer’s Disease

Objective: The authors evaluated the psychometric properties and clinical utility of the Loewenstein-Acevedo Scale for Semantic Interference and Learning (LASSI-L), in patients with amnestic Mild Cognitive Impairment (aMCI) and early Alzheimer’s disease (AD). Methods: Subjects were administered Target List A and instructed to remember 15 common words belonging to a specific semantic category, using multi-modal, active encoding procedures. After free recall and cued recall trials of the target list, a second learning trial was offered, followed by a cued recall trial, to facilitate the initial acquisition of targets. Thereafter, the subject was exposed to a semantically-related List B, which was administered in the same manner as Target List A. Test-retest reliability, concurrent and discriminative validity were assessed. LASSI-L measures were then correlated with Magnetic Resonance Imaging (MRI) measurements of medial temporal lobe atrophy (MTA). Results: High test-retest, concurrent and discriminative validity was obtained for LASSI-L subscales, and MTA atrophy scores were highly and negatively correlated with LASSI-L indices. Conclusion: Subtests of the LASSI-L demonstrate high reliability and validity, and are strongly associated with MRI biomarkers of early neurodegenerative disease. It is concluded that the LASSI-L is a highly promising test for the assessment of mild cognitive impairment and early AD among the elderly.

Cognitive and structural magnetic resonance imaging features of Lewy body dementia and Alzheimer’s disease

To assess medial temporal atrophy (MTA) and atrophy adjacent to the third ventricle (Peri‐IIIVent) on brain magnetic resonance images as biomarkers for the diagnosis of Alzheimers disease (AD) and Lewy body dementia (LBD), and to assess the relationship between biomarkers and clinical and functional measures.