Predicting the Transition to Alzheimer Disease

About 16% of people with mild cognitive impairment (MCI) progress to Alzheimer disease during the course of a year, according to new data from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Progression from MCI to AD, which correlated with baseline CSF levels of amyloid beta-42, occurred despite the prevalent use of available antidementia therapies (~50% of subjects).

ADNI investigators followed up more than 800 elderly subjects (mean age, ~75 years) with normal cognition, MCI, or AD. Baseline data were notable for remarkably high mean verbal IQ scores and education levels among all 3 groups and relatively high percentages of APOEε4 carriers among individuals with MCI or AD.

Baseline Feature	Normal   (n = 229)	MCI (n = 398)	AD (n = 192)	P Value
Mean education, y	16 ± 2.9	15.7 ± 3.0	14.7 ± 3.1	<.001*
Estimated mean premorbid verbal IQ	120	116	114	—
APOEε4 carriers, %	26.6	53.3	66.1	<.001*
Mean MMSE score	29.1 ± 1.0	27.0 ± 1.8	23.3 ± 2.1	<.001**
Mean ADAS-cog score	6.2 ± 2.9	11.5 ± 4.4	18.6 ± 6.3	<.001**
AChEI, %	0	43.7	84.9	—
Memantine, %	0	10.8	47.4	—
Combined therapy, %	0	8.8	40.6	—
Mean CSF Aβ-42 level, pg/mL	206 ± 5	164 ± 4	143 ± 4	<.001**

* Control vs MCI amd MCI vs AD.
** Control vs MCI; control vs AD; and MCI vs AD.

On the basis of a battery of cognitive and neuropsychological tests, the estimated rate of conversion from normal cognition to MCI was 1.4% during 12 months, and that from MCI to AD was 16.5%. Eight individuals with MCI reverted to normal cognition, and 2 subjects with AD reverted to MCI at 1 year. 

Among individuals with MCI, scores on a range of assessments (eg, MMSE, ADAS-cog, clock drawing) could be used to predict progression to AD. Lower CSF levels of amyloid beta-42, which did (and are known to) correlate with higher ADAS-cog scores, were also associated with cognitive decline in normal people and those with MCI. 

In July, the ADNI reported that structural abnormalities on MR images are more useful than known CSF biomarkers for discriminating among people with AD, amnestic MCI, or normal cognition, but that the use of MR imaging and CSF analysis is more diagnostically helpful than each measure individually.

AChEI = acetylcholinesterase inhbitor; ADAS-cog = Alzheimer's Disease Assessment Scale, Cognitive Subscale; APOE = apolipoprotein E; CSF = cerebrospinal fluid; MMSE = Mini-Mental State Examination; MR = magnetic resonance.

Photograph: Atrophied brain of person with AD from National Institute on Alcohol Abuse and Alcoholism.