Early warning signs of Alzheimer’s show up across cognitive areas years before official diagnosis

Swedish meta-analysis of 47 scientific studies finds clear patterns across thousands of people who went on to be diagnosed with the disease

By combing through dozens of Alzheimer’s disease (AD) studies, psychologists have gained a clear picture of cognitive problems in people who will develop the degenerative brain disease. The meta-analysis reveals that people can show early warning signs across several cognitive domains years before they are officially diagnosed, confirming that Alzheimer’s causes general deterioration and tends to follow a stable preclinical stage with a sharp drop in function. The findings appear in the July issue of Neuropsychology, which is published by the American Psychological Association.

Researchers at the Karolinska Institute and Stockholm Gerontology Research Center, affiliated also with the Max Planck Institute for Human Development and the University of South Florida, crunched the data from a decade’s worth of studies: Published reports that met stringent criteria had records on 1,207 people with preclinical Alzheimer’s (they later developed the disease) and 9,097 controls who stayed healthy.

Neuropsychologists are striving to understand the preclinical stage for two reasons: On the theoretical level, understanding the transition from normal aging to dementia is vital to understanding how the disease evolves. On the clinical level, treatment can work best when doctors can identify at-risk individuals as early as possible.

The authors studied 47 peer-reviewed studies published between January 1985 and February 2003. The year 1985 marked the introduction of more systematic and reliable diagnostic criteria for Alzheimer’s.

The analysis showed that no matter what kind of study, people at the preclinical stage showed marked preclinical deficits in global cognitive ability, episodic memory, perceptual speed, and executive functioning; along with somewhat smaller deficits in verbal ability, visuospatial skill, and attention. There was no preclinical impairment in primary memory.

The generalized nature of the problem is consistent, say the authors, with recent observations that multiple brain structures and functions are affected long before the AD diagnosis. They remind readers that the deficits seen in preclinical AD mirror quite closely those seen in normal aging, such as impairments in episodic memory, executive functioning, and cognitive speed. Still, says lead author Lars Bäckman, PhD, these problems are exacerbated in those who will go on to be diagnosed with dementia.

He explains, “There are no clear qualitative differences in patterns of cognitive impairment between the normal old 75-year old and the preclinical AD counterpart. Rather, we think of the normal elderly person, the preclinical AD person, and the early clinical AD patient as representing three instances on a continuum of cognitive capabilities. This presents an obvious challenge for accurate early diagnosis.”

The data also supported the emerging consensus that AD’s preclinical period is characterized by an early onset followed by relative stability until a few years before diagnosis, when functioning plummets.

Bäckman and his colleagues endorse a multi-variable approach to understanding the preclinical stage of AD because this approach will help clinicians to more accurately predict the likelihood of disease.

The study traced other interesting patterns. People younger than 75 years at baseline were more impaired at the outset than people older than 75 at baseline. Impairment was also greater for the patients with shorter periods (fewer than three years) to diagnosis. These findings suggest that preclinical impairment is greater when the disease starts younger and progresses more quickly, due to more widespread and severe brain lesions among younger cases.