Memory impairment, but not cerebrovascular disease, predicts progression of MCI to dementia

DeCarli, Charles; Mungas, Dan M; Harvey, Danielle; Reed, Bruce R; Weiner, Michael W.; Chui, Helena C.; Jagust, William J.

doi:10.1212/01.wnl.0000130531.90205.ef

Cited by 244 publications

(205 citation statements)

References 60 publications

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“…In addition, MCI subjects with greater hippocampal atrophy at baseline are more likely to convert to AD (Jack et al, 1999;Visser et al, 1999;Killiany 2000;Dickerson et al, 2001;Killiany et al, 2002;Adak et al, 2004;DeCarli et al, 2004). In this study however, hippocampal volumes at baseline in APOE ∈4 carriers treated with donepezil (5062 mm 3 , SD 773 mm 3 ) were not different from those treated with placebo (4916 mm 3 , SD 744) (p= 0.51) ( Table 1).…”

Section: Effect Of Treatment On Mri Atrophy Ratesmentioning

confidence: 50%

“…This is consistent with other longitudinal MRI studies (Hashimoto et al, 2005) as well as a large body of literature on the biologic effect of APOE ∈4 indicating that carriers have an increased probability of developing AD and an increased likelihood of converting from MCI to AD than non carriers (Corder et al, 1993;Petersen et al, 1995). Studies evaluating the relationship between APOE ∈4 status and brain morphometry have found effects consistent with greater disease severity, an independent contribution of APOE ∈4 and atrophy to clinical disease severity, and greater likelihood of clinical progression in APOE ∈4 carriers (Plassman et al, 1997;den Heijer et al, 2002;Adak et al, 2004;DeCarli et al, 2004;Farlow et al, 2004;Fleisher et al, 2005). The effect of APOE ∈4 on MRI rates observed in this MRI sub study is consistent with the results in the main treatment study in which APOE ∈4 carriers in each treatment group (donepezil, vitamin E, and placebo) were more likely to convert to AD than non carriers.…”

Section: Discussionmentioning

confidence: 98%

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Longitudinal MRI findings from the vitamin E and donepezil treatment study for MCI

Jack

Petersen

Grundman³

et al. 2008

Neurobiology of Aging

133

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The vitamin E and donepezil trial for the treatment of amnestic mild cognitive impairment (MCI) was conducted at 69 centers in North America; 24 centers participated in an MRI sub study. The objective of this study was to evaluate the effect of treatment on MRI atrophy rates; and validate rate measures from serial MRI as indicators of disease progression in multi center therapeutic trials for MCI. Annual percent change (APC) from baseline to follow-up was measured for hippocampus, entorhinal cortex, whole brain, and ventricle in the 131 subjects who remained in the treatment study and completed technically satisfactory baseline and follow-up scans. Although a non-significant trend toward slowing of hippocampal atrophy rates was seen in APOE ∈4 carriers treated with donepezil; no treatment effect was confirmed for any MRI measure in either treatment group. For each of the four brain atrophy rate measures, APCs were greater in subjects who converted to AD than non-converters, and were greater in APOE ∈4 carriers than non-carriers. MRI APCs and changes Disclosure Statement for AuthorsThe authors have no conflicts of interest to disclose. The industry sponsors had no role in the analysis or interpretation of these data nor in the content of the paper. Appropriate approval procedures were used concerning human subjects. NIH Public Access IntroductionThe vitamin E and donepezil clinical trial for the treatment of mild cognitive impairment (MCI) was conducted in 769 subjects at 69 centers in North America . The study was designed to determine whether the antioxidant vitamin E or donepezil, the only cholinesterase inhibitor available at the time the study was designed, would be effective at delaying the clinical progression of subjects with the amnestic form of MCI to the clinical diagnosis of Alzheimer's disease (AD). While vitamin E had no beneficial effect, donepezil reduced the risk of progression from amnestic MCI to clinically possible or probable AD for up to 12 months. This treatment effect was extended to 24 months in carriers of the apolipoprotein E ∈4 (APOE e4) allele. Twenty-four of the recruiting sites voluntarily participated in a Magnetic Resonance Imaging (MRI) sub study which was grafted onto the existing clinical therapeutic study design. The purpose of the MRI sub study was to determine if a therapeutic effect of either vitamin E or donepezil could be detected on rates of brain atrophy from serial MRI studies. Four different brain atrophy brain measures were assessed; the hippocampus, entorhinal cortex (ERC), whole brain, and ventricular volume. Each of these MRI measurements has figured prominently in anatomic MRI based studies of MCI, AD, and normal aging (Jack et al., 1992;Fox et al., 1996;Jack et al., 1997;Fox et al., 1999;Killiany 2000;Dickerson et al., 2001;Killiany et al., 2002;Du et al., 2003). A primary objective of this analysis was to test the hypothesis that vitamin E or donepezil slowed the rate of brain atrophy relative to placebo in subjects with amnestic MCI (Petersen 1995;Pe...

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Section: Effect Of Treatment On Mri Atrophy Ratesmentioning

confidence: 50%

Section: Discussionmentioning

confidence: 98%

Longitudinal MRI findings from the vitamin E and donepezil treatment study for MCI

Jack

Petersen

Grundman³

et al. 2008

Neurobiology of Aging

133

View full text Add to dashboard Cite

show abstract

“…Cognitive impairment without dementia, as defined in the present study, is a broad classification [41] with a high prevalence in diabetes [42]. Mild cognitive impairment is a more restrictive category with a high rate of transition to dementia, but it has recently been shown that the subgroup of mild cognitive impairment associated with CVD is less likely to progress to dementia [43]. Follow-up studies will be required to determine whether these patients will progress to dementia.…”

Section: Discussionmentioning

confidence: 79%

Predictors of cognitive impairment and dementia in older people with diabetes

et al. 2007

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Aims/hypothesis Diabetes is associated with an increased risk of dementia but the reasons for this association are unclear because there are many potential mechanisms. We explored the relative contribution of diabetes-related variables as predictors of dementia in older individuals with diabetes. Methods Survivors, aged ≥70 or more, were recruited from an existing observational cohort study 7.6±1.0 years after baseline, when they underwent a comprehensive assessment of diabetes, complications and cardiovascular risk factors. Dementia, probable Alzheimer's disease and cognitive impairment without dementia were diagnosed clinically. Logistic regression modelling determined independent predictors of cognitive diagnoses. Results Of 302 participants, aged 75.7±4.6 years, 28 (9.3%) had dementia (16 with probable Alzheimer's disease) and 60 (19.9%) had cognitive impairment without dementia. The major independent longitudinal predictors of dementia were older age (per decade; odds ratio 4.0, 95% CI 1.59-10.10), diabetes duration (for each 5 years; odds ratio 1.69, 95% CI 1.24-2.32), peripheral arterial disease (odds ratio 5.35, 95% CI 2.08-13.72) and exercise (which was protective; odds ratio 0.26, 95% CI 0.09-0.73). For Alzheimer's disease, diabetes duration was an independent predictor in addition to age and diastolic blood pressure. The results of the cross-sectional analyses were similar with respect to diabetes duration and peripheral arterial disease. Conclusions/interpretation Peripheral arterial disease is a strong independent risk factor for dementia in diabetes. After adjustment for a wide range of potential risk factors, diabetes duration remains independently associated with dementia and probable Alzheimer's disease, indicating that factors not measured in this study may be important in the pathogenesis of dementia in diabetes.

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“…Whether this is a generalizable finding, however, requires further study. For example, the research on the comparative value of imaging and cognitive predictors of conversion from MCI to dementia, a change defined in part by decreasing everyday function, is quite mixed (DeCarli et al, 2004;Korf et al, 2004;Visser et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Cognitive and neuroimaging predictors of instrumental activities of daily living

Cahn-Weiner

Farias

Julián

et al. 2007

J. Inter. Neuropsych. Soc.

187

167

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Impaired ability to conduct daily activities is a diagnostic criterion for dementia and a determinant of healthcare services utilization and caregiver burden. What predicts decline in instrumental activities of daily living (IADLs) is not well understood. This study examined measures of episodic memory, executive function, and MRI brain volumes in relation to baseline IADLs and as predictors of rate of IADL change. Participants were 124 elderly persons with cognitive function between normal and moderate dementia both with and without significant small vessel cerebrovascular disease. Random effects modeling showed that baseline memory and executive function (EXEC) were associated with baseline IADL scores, but only EXEC was independently associated with rate of change in IADLs. Whereas hippocampal and cortical gray matter volumes were significantly associated with baseline IADL scores, only hippocampal volume was associated with IADL change. In a model including cognitive and neuroimaging predictors, only EXEC independently predicted rate of decline in IADL scores. These findings indicate that greater executive dysfunction at initial assessment is associated with more rapid decline in IADLs. Perhaps executive function is particularly important with respect to maintaining IADLs. Alternatively, executive dysfunction may be a sentinel event indicating widespread cortical involvement and poor prognosis.

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Memory impairment, but not cerebrovascular disease, predicts progression of MCI to dementia

Cited by 244 publications

References 60 publications

Longitudinal MRI findings from the vitamin E and donepezil treatment study for MCI

Longitudinal MRI findings from the vitamin E and donepezil treatment study for MCI

Predictors of cognitive impairment and dementia in older people with diabetes

Cognitive and neuroimaging predictors of instrumental activities of daily living

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