| Article Access Statistics|
| Viewed||2538 |
| Printed||24 |
| Emailed||0 |
| PDF Downloaded||50 |
| Comments ||[Add] |
Click on image for details.
|NI FEATURE: THE EDITORIAL DEBATE I-- PROS AND CONS
|Year : 2018 | Volume
| Issue : 2 | Page : 326-327
MR volumetry in mild cognitive impairment (MCI) – A useful marker to predict progression
Department of Neurology, Manipal Hospital, Bangalore and Annasawmy Mudaliar General Hospital, Bangalore, Karnataka, India
|Date of Web Publication||15-Mar-2018|
Dr. Ellajosyula Ratnavalli
Department of Neurology, Manipal Hospital, Bangalore and Annasawmy Mudaliar General Hospital, Bangalore, Karnataka
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Ratnavalli E. MR volumetry in mild cognitive impairment (MCI) – A useful marker to predict progression. Neurol India 2018;66:326-7
Mild cognitive impairment (MCI) is an intermediate stage between age associated cognitive impairment and dementia. In general, a person with cognitive complaints, and the findings of its impairment on testing but with normal functioning, will be characterized as having MCI. It can be classified based on the underlying cognitive deficit (amnestic or non-amnestic) or the number of domains affected (single versus multiple). MCI is a heterogeneous condition with several causes like depression, medications, alcohol use, and chronic medical diseases that need to be ruled out. Though the concept of MCI has generated controversy, it is a useful clinical construct because it helps clinicians communicate the diagnosis to patients who have cognitive impairment but do not meet the criteria for dementia. In addition, MCI is a target for disease-modifying agents. It enables an early intervention in order to prevent or delay the development of dementia.
MCI estimates are about 12-18% among older adults above the age of 60 years. The annual progression rate/year is around 10% though there is wide variation based on population or specialist memory clinic data. MCI can also remain stable or improve but it is important to note that even in studies where it appeared to improve, most patients ultimately progressed to dementia. The amnestic form (aMCI), in particular, has been considered an early stage of Alzheimer's disease (AD).
There are two important issues in the approach to a patient with MCI in the clinic. One is the way to identify patients who are at an increased risk of dementia. Sheelakumari and colleagues have compared 24 patients with aMCI, 13 with early AD and 25 healthy controls using voxel-based morphometry (VBM) and automated regional volumetry (ARV) techniques to quantify the gray matter volumes on magnetic resonance imaging (MRI) of the brain. All subjects also underwent Addenbrooke's cognitive examination (ACE) and Rey Auditory Verbal Learning Test (RAVLT), which have been adapted to the local population. The aMCI group was stable; the group did not have patients progressing to AD over a study period of 1.5 years. The major findings in this study were that the aMCI group had a predominant atrophy in the superior temporal gyrus, left hippocampus and mesial frontoparietal regions while the AD group showed more extensive atrophy in the limbic region (especially the parahippocampal gyrus, bilateral hippocampi and amygdala), temporal neocortex and precuneus. Atrophy measures were significant compared to controls for both the patient groups. The AD group showed more regional atrophy than the MCI group but these differences were not significant. Only the overall gray matter atrophy was significant between the two groups. Memory learning and recall correlated with left hippocampal volume in MCI and with right temporal neocortex in AD patients. Quantitative MR imaging in MCI patients using VBM is a novel observation for India. These MR imaging techniques need infrastructure, trained personnel and are time consuming. Most studies in the West have used these quantitative MR techniques for more than a decade for identifying the imaging markers of MCI and preclinical AD. Some studies have shown that visual rating using a standardized scale, which is quicker and simpler, seems to perform nearly as well. A prospective study following MCI patients with imaging and neuropsychological testing to identify the markers indicating the progression to dementia would be useful in our setting.
Use of robust memory tests adapted to the language and practices of the local population added strength to the study. The major drawback, which the authors themselves point out, is the short duration of 1.5 years over which they designated the aMCI as being stable or non-progressive. This duration appears inadequate and most studies report a minimum of 3-5 years. It is surprising that MCI patients in this study had a relatively long duration of symptoms (5.8 ± 3.7 years; range 2.1-9.5 years). The authors do not mention comorbid conditions and also anxiety, though they ruled out depression, which may have contributed to the symptoms. It is also interesting that the memory measures correlated with the left hippocampus as expected in MCI, but unexpectedly with the right temporal cortex in the AD group. Verbal memory measures are expected to correlate with the left side. This is a surprising finding, which has not been discussed. In a meta-analysis of VBM studies from 429 aMCI patients, of whom 142 converted to AD, the gray matter volumetric reduction in the medial temporal lobe (left hippocampus and parahippocampal gyrus) was the consistent biomarker to predict conversion from aMCI to AD. The National Institute of Aging and Alzheimer's Association have also formulated criteria for diagnosing MCI using biomarkers. For instance, the stable MCI patients in this study have an intermediate probability of belonging to the AD group, as they had atrophy in the mesial temporal region, considered a neuronal marker of injury.
The relationship between depression and MCI is complicated. Depression may be seen in 25-40% patients with MCI. Depression is associated with an increased risk of MCI in normal elderly subjects, and also in the case when MCI is associated with an increased risk of progression to dementia. It was customary to exclude depression in clinical trials of MCI but doing so greatly reduces the sensitivity of diagnosis of AD.
The second important issue in dealing with a patient with MCI would be to reverse cognitive impairment if possible, or to delay the conversion rate to dementia. Treating depression and other comorbid medical conditions, addressing vascular risk factors, withdrawing medications causing cognitive impairment, indulging in cognitive activities, and being engaged with life and physical exercise are some of the strategies in the management of MCI. Only the last factor, physical exercise, has been shown to be beneficial in studies  but it is a good clinical practice to follow the other measures as well. We should direct our efforts to diagnosing patients early, suggesting interventions and in having a close follow up. Initiating cholinesterase inhibitors in MCI patients is a poor clinical practice and there is no evidence to support it.
| » References|| |
Petersen RC. Mild Cognitive Impairment. Continuum (Minneap Minn) 2016;22:404-18.
Roberts RO, Knopman DS, Mielke MM, Cha RH, Pankratz VS, Christianson TJ, et al
. Higher risk of progression to dementia in mild cognitive impairment cases who revert to normal. Neurology 2014;82:317-32.
Sheelakumari R, Kesavadas C, Leka VS, Justus S, Sarma PS and Menon R. Structural correlates of mild cognitive impairment: A clinicovolumetric study. Neurol India 2018;66:370-76. [Full text]
Geroldi C, Rossi R, Calvagna C, Testa C, Bresciani L, Binetti G, et al
. Medial temporal atrophy but not memory deficit predicts progression to dementia in patients with mild cognitive impairment. J Neurol Neurosurg Psychiatry 2006;77:1219-22.
Ferreira LK, Diniz BS, Forlenza OV, Busatto GF, Zanetti MV. Neurostructural predictors of Alzheimer's disease: A meta-analysis of VBM studies. Neurobiol Aging 2011;32:1733-41.
Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, et al
. The diagnosis of mild cognitive impairment due to Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement 2011;7:270-9.
Visser PJ, Scheltens P, Verhey FR. Do MCI criteria in drug trials accurately identify subjects with predementia Alzheimer's disease? J Neurol Neurosurg Psychiatry 2005; 76:1348-54.
Suzuki T, Shimada H, Makizako H, Doi T, Yoshida D, Ito K, et al
. A randomized controlled trial of multicomponent exercise in older adults with mild cognitive impairment. PLoS one 2013;8:61483.