Munir Chowdhury

Is Mild Cognitive Impairment Prodromal for Vascular Dementia Like Alzheimer’s Disease?

Background and Purpose Individuals with mild cognitive impairment (MCI) are at increased risk of Alzheimer’s disease (AD) and probably other forms of dementia. Some subtypes of vascular dementia (VaD) may possess minor neuropathological changes of AD that may contribute to cognitive impairments. It was posited that MCI, identified by criteria described here, might present as a prodrome for VaD and AD. Methods— Serial Mini-Mental State Examination was administered at 3- to 6-month intervals, and neuroimaging was performed annually. Subtle cognitive dysfunctions were weighted and measured according to MCI criteria defined here. Subjects identified with MCI were then followed up for an additional 3.88±3.01 years. Diagnoses of VaD and AD were made according to established criteria. Results— During 3.72±2.94 years of follow-up of the original normative subjects, 73 of 291 (25.1%) developed MCI. Of the 27 subjects who developed VaD, 15 (55.6%) had prodromal MCI. Of these, two thirds were subclassified as having small-vessel dementia. The remaining 12 patients with VaD (44.4%) were diagnosed directly from a cognitively normal status without preceding MCI. These were predominantly multi-infarct or strategic-infarct dementia (66.7%). An additional 35 MCI subjects (47.9%) developed AD. Both VaD and AD diagnosed after MCI prodromes manifested similar spectral domains of cognitive impairments, which included memory, during their MCI stages. Conclusions— In some VaD subtypes, particularly those caused by subcortical microvascular disease, dementia may be preceded by MCI, which has similar domains of cognitive impairment and a similar progressive course that may mimic AD.

Longitudinal analysis of abnormal domains comprising mild cognitive impairment (MCI) during aging

Research directed towards early diagnosis and therapy of dementia demands rapid identification of prodromal mild cognitive impairment (MCI). A longitudinal study was designed to clarify whether different domains of cognitive impairment, tested by Mini-Mental State Examination (MMSE), help predict dementia. After 3.74+/-2.94 years of follow-up among 291 cognitively normative volunteers, 73 developed MCI. During the next 3.88+/-3.01 years of MCI follow-up, 47.9% of MCI developed dementia of Alzheimers type (DAT), 20.5% of MCI developed vascular dementia (VaD) and 31.5% maintained persistent MCI at the time of data analysis. Total MMSE and subtest scores analyzed at MCI onset showed significant differences for serial seven subtest scores between DAT and persistent MCI (P<0.05). Rates of change in subtests of orientation and memory and total MMSE scores predicted DAT (P<0.01). Decreasing orientation and total MMSE scores predicted VaD conversion rates of MCI to DAT at 2 years were 20.06% among single-domain MCI versus 41.7% for multi-domain MCI (P<0.05). Subjects with MCI often have impaired cognitive domains other than memory and show rapid deterioration, which predicts DAT. VaD sometimes mimics DAT with subtle cognitive impairment appearing before onset of dementia.

MRI confirms mild cognitive impairments prodromal for Alzheimer's, vascular and Parkinson-Lewy body dementias.

OBJECTIVES MRI assessments were correlated with serial Combined Mini-Mental Cognitive Capacity Screening Examinations (CMC). Vascular-MCI (VMCI), Neurodegenerative MCI (NMCI) and Parkinson-Lewy body MCI (PLB-MCI) were compared during conversions to dementia. Mild cognitive impairments (MCI) are identifiable prodromes for all dementia subtypes. MRI abnormalities are characterized among MCI subjects prodromal for dementia of Alzheimers disease (DAT), vascular dementia (VaD) and Parkinson-Lewy body dementia (PLBD). METHODS Aging volunteers (n=166) were recruited from ongoing longitudinal studies of aging, stroke, cerebrovascular disease and dementia. Cognitively normal (CN, n=52), MCIs of neurodegenerative (N-MCI, n=30), vascular (V-MCI, n=35) and Parkinson-Lewy Body (PLB-MCI, n=8) subtypes, plus converted DAT (n=19), VaD (n=17) and PLBD (n=5) were all diagnosed according to established protocol recommendations. Cerebral MRI abnormalities were likewise intercorrelated utilizing quantitative volumetric measurements. RESULTS V-MCI and converted VaD showed extensive leukoaraiosis with more lacunar infarcts than subjects with N-MCI or PLB-MCI. N-MCI, prodromal for DAT, showed medial temporal atrophy, greater enlargement of temporal horns, and fewer vascular lesions. PLB-MCI, prodromal for PLBD, displayed third ventricular enlargement greater than N-MCI and V-MCI, with similar but less severe atrophy of medial temporal lobe than N-MCI and fewer vascular lesions than V-MCI. Cognitive Impairments due to PLB with vascular features (V-PLB-CI) showed more lacunar and microvascular lesions involving both white matter and basal ganglia with greater frontal horn enlargement. CONCLUSIONS This study confirms different MCI subtypes prior to conversion to different dementias listed, recognizable by specific MRI abnormalities.

Progression of Mild Cognitive Impairment to Alzheimers or Vascular Dementia Versus Normative Aging Among Elderly Chinese

To compare differences in evolutionary progressions from Mild Cognitive Impairment (MCI) to dementia of Alzheimers type (DAT) or to vascular dementia (VaD) versus normal aging, subjects identified as MCI or as cognitively normal (CN) during standard cognitive evaluations among a large epidemiological study designed to determine prevalence and incidence of dementia and its major subtypes in Beijing, China were re-examined after an interval of approximately 3 years, repeating the same investigation protocol as at baseline. MCI subjects meeting criteria for dementia and the two major subtypes, DAT and VaD were identified at follow-up evaluation. Annual conversion rates for combined dementias and for major subtypes of DAT and VaD, from MCI, were compared with conversion rates among CN subjects. Relative risks for conversion from MCI to major subtypes of dementia were also compared with CN subjects by Cox regression models. 175 MCI and 400 CN subjects were identified at baseline. Among 121 MCI subjects available at follow-up, 51 were diagnosed with dementia (29 with DAT, 18 with VaD and 4 with other dementias), compared with 14(10 DAT, 3 VaD and 1 other type dementia) diagnosed as dementia among 281 CN subjects available at follow-up. Annual conversion rates calculated from MCI to all dementias, compared with conversion rates from CNs, were 14.1% versus 1.6%. Specifically for DAT, annual conversion rates were 8.0% versus 1.1% and for VaD were 5.0% versus 0.3%. Relative risks for developing all dementias, DAT and VaD among MCI subjects were 9, 6 and 5 times greater than among CN subjects. Conversion rates among MCI subjects to dementia, and major subtypes, for elderly Chinese residents of Beijing were comparable with results reported among similar studies worldwide. Risks of developing dementia, and major subtypes, among MCI subjects in Beijing were significantly higher than among normal subjects. Identification of MCI among elderly populations provides the possibilities for dementia prevention and treatment within prodromal stages.

MRI identifies MCI subtypes: vascular versus neurodegenerative

As life expectancy increases worldwide, pandemics of cognitive impairment and dementia are emerging as major public health problems. Mild cognitive impairment (MCI), prodromal for dementia, is a descriptive term used for those clinical states showing early and subtle cognitive decline among the elderly, preceding the dementias. Psychometric screening combining Mini-Mental Status (MMSE) and Cognitive Capacity Screening (CCSE) Examinations, when combined now called CMC with C standing for Combined, M for MMSE, and C for CCSE, confirms diagnosis of MCI. Individuals identified with MCI are at increased risk for dementia of Alzheimers type (DAT), vascular dementia (VAD) and other rare neurodegenerative dementias, including Lewy body dementia (LBD), fronto-temporal dementia (FTD) and Parkinsons disease dementia (PDD). Depending on different clinical compositions of cohorts studied, and MCI criteria used, between 19% and 50% of MCI progress to dementia within 3-5 years, two thirds to Alzheimers (DAT) and one third to vascular types (VAD) in the United States. Not all Parkinsonians become demented, but PDD develops in 20-30%, however, PDD subjects were excluded from the present study, as were LBD and FTD. The incidence of MCI in those over age 70, with confirmed cognitive declines when tested 2 years later, is around 23%, but some spontaneously improve.

Donepezil Treatment of Vascular Dementia

Abstract: Cholinergic deficits are clinicopathological hallmarks of Alzheimers disease (DAT) and during the past decade have been the sole target for clinically effective treatments. By contrast, vascular dementia subtypes (VaD) are heterogeneous clinical syndromes, and therapeutic approaches have been directed toward control of vascular risk factors. Little attention has been paid to cholinergic deficits as a mechanism contributing to cognitive impairments in VaD as a potential target for treatment. The purpose of the study was to determine whether there are therapeutic benefits from long‐term treatment with cholinesterase inhibitors among VaD patients. Ten VaD patients were diagnosed according to DSM‐III‐R and NINDS‐AIREN criteria and classified into subtypes by neuroimaging. All were treated with titrated doses of donepezil for a mean interval of 15 months. At baseline and follow‐up clinic visits, patients underwent medical and neurological examinations, as well as neuropsychological testing including Mini‐Mental Status Examinations (MMSE) and Cognitive Capacity Screening Examinations (CCSE). Cognitive statuses of 10 treated patients were then compared before and after treatment. Net changes were expressed as annual MMSE score changes (ΔMMSE/year) and annual CCSE score changes (ΔCCSE/year). Of the 10 treated VaD patients, cognitive improvements were found when comparisons were made before and after treatment. Ten treated patients also showed greater cognitive improvements, while untreated patients showed continued cognitive decline. This study suggests that cholinergic deficits in VaD are due to neuronal ischemic damage with loss of acetylcholine and that treatment of VaD with cholinesterase inhibitors is a rational therapy.

Combined mild diabetes with hypertension during aging increases white matter atrophy

A.M. Tiehuis, W.P. Mali, A.F. van Raamt, G.J. Biessels, L.J. Kappelle, F.L. Visseren, Y. van der Graaf Department of Radiology, University Medical Center, Utrecht, The Netherlands Julius Center For Health Sciences and Primary Care, University Medical Center, Utrecht, The Netherlands Department of Neurology, University Medical Center, Utrecht, The Netherlands Department of Internal Medicine, University Medical Center, Utrecht, The Netherlands