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

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Abstract

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 Alzheimer's 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.

Introduction

Identification of individuals at risk for dementia in order to begin early therapeutic interventions is vitally important, because resulting cognitive and neurobehavioral improvements should lessen distress for patients, families and caregivers as well as minimizing risk of accidents, prolonging personal autonomy, possibly preventing onset and even halting the dementia process and formulating backup plans for future care, if necessary [1]. For these reasons, increasing attention is now being devoted to the interphases between normal aging and dementia, characterized by cognitive impairments that are insufficient to meet criteria for dementia [2].

Beginning in the early 1960s, these interphase cognitive impairments were labeled with various tags, the popularity of which has fluctuated from time to time, often influenced by support from different health organizations. Nosological terms have included “benign senescent forgetfulness” through the 1960s and 1970s [3], “age-associated memory impairments” (AAMI) in the 1980s recommended by the National Institute of Mental Health [4], and recently “age-associated cognitive decline” (AACD) recommended by the World Health Organization (WHO) [5], “cognitive impairment no dementia” (CIND) recommended by the Canadian Study of Health and Aging [6] and “mild cognitive impairment” (MCI) now recommended by the American Academy of Neurology (AAN) [7]. “Vascular cognitive impairment” (VCI) has recently been suggested to depict cognitive impairment attributable to impending or actual vascular dementia (VaD) [8], [9]. The prevalence, incidence and rates of conversion to dementia among these separately labeled transitional stages have varied widely due to different identification criteria, even when applied to populations with comparable demographics [1]. MCI, the term to be used here, is now the most frequently endorsed for describing transitional stages between normal aging and incipient dementia.

A number of studies have documented increased risk of dementia of Alzheimer's type (DAT) among MCI subjects [10], [11], [12]. However, inability to distinguish MCI that progress to dementia from those who do not still hinders prevention and early treatment of dementia. According to present criteria, if MCI subjects are treated unselectively in the hope of delaying or preventing dementia, potential risks result, which should be weighed against any benefits among healthy but frail elderly individuals treated with cholinesterase inhibitors, or vaccines, which may have adverse side effects [13], [14], [15], [16]. A possible solution for this dilemma is to analyze the cognitive impairment domains of MCI based on the hypothesis that particular domains of cognitive impairments may act as signal flags for those who will progress to dementia. There is little disagreement that memory dysfunction is a primary predictor for DAT [17], [18]. Petersen et al. [12] have suggested that in MCI general intellectual functioning should be preserved with memory being solely affected. Other investigators disagree and consider that cognitive domains besides memory may also become impaired, such as language [16], [19], orientation [20], [21], attention, concentration [22], [23] and praxis [16], [20]. To clarify such questions and confounds, further investigations, particularly longitudinal observations, should be helpful.

Section snippets

Subjects

Subjects for this research comprise volunteers enrolled in longitudinal studies of aging and dementia inaugurated in 1983 and approved annually by Institutional Review Boards of Baylor College of Medicine. These volunteers are all dwellers in and around Houston metropolitan areas. Many volunteers were relatives, caregivers and friends of our patients with stroke, VaD and DAT and so many had risk factors for stroke. This bias accounts for the high incidence of VaD developing in this population

Results

During 3.72±2.94 years of follow-up, 73 out of 291 cognitively normative subjects developed MCI and completed one or more visits after MCI identification. After an additional 3.88±3.01 years of MCI follow-up, the original 73 MCI subjects became differentiated into three groups: 35 (47.9%) developed DAT, 15 (20.5%) developed VaD and 23 (31.5%) MCI persisted at the time follow-up was closed for data analysis or dropped out (by death, moving out of the area or refusal to continue). Demographic

Discussion

This longitudinal study confirms that MCI subjects are at high risk for dementia, particularly DAT. Individuals with MCI, however, may have one or more cognitive domains impaired other than memory. Impairments of special cognitive domains and deterioration rates predict DAT. Multi-domain MCI is more likely to progress to DAT than single-domain MCI. These conclusions are partly supported by reports of others [1], [5], [17], [18], [20], [21], [22].

Previous investigations have reported that

Acknowledgements

This study was supported by the Department of Veterans Affairs Central Office in Washington, DC, Meyer Research Foundation of Baylor College of Medicine. Felicia Cruise, Yansheng Li, Melissa Phinney and Peter Hinh helped in collecting clinical data and Irma Muniz and Cora Bess Meyer provided administrative assistance.

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