β-amyloid cleared of blame for early memory decline

By Eleanor McDermid, Senior medwireNews Reporter

A “seminal” imaging study suggests that worsening memory in adults is not necessarily an indicator of β-amyloid deposition.

Memory function declined in line with older age of the study participants, but marked decreases in memory and hippocampal volume occurred well before the age at which β-amyloid accumulation was observed.

This contradicts the conventional wisdom that most cognitive decline and dementia in the general population is a consequence of incipient Alzheimer’s disease, says Charles DeCarli (University of California at Davis, Sacramento, USA), in an editorial accompanying the study in JAMA Neurology.

In 37 volunteers, aged 30 to 49 years, hippocampal volume adjusted for brain structure was 0.18 cm³. In 1209 participants of the Mayo Clinic Study of Aging (MCSA), aged between 50 and 95 years, this value decreased with age, from –0.15 cm³ in those aged 50 to 64 years to –0.99 and –1.76 cm³ in those aged 65 to 79 years and 80 to 95 years, respectively.

Likewise, participants’ adjusted Auditory Verbal Learning Test scores were 5 points in the young volunteers, and declined to –6, –17 and –30 points in the younger, middle and oldest age groups, respectively, of the MCSA participants.

Declines in both memory and hippocampal volume became especially marked among participants in their mid-60s and older. However, the declining trends were “well established” before this, despite only a very slight upwards trend in β-amyloid deposition among participants below the age of 70 years.

This indicates that age-related declines “in memory and hippocampal volume “must have some mechanistic independence from β-amyloid accumulation”, say Clifford Jack (Mayo Clinic, Rochester, Minnesota, USA) and study co-authors.

There was a steeper increase in median β-amyloid levels from the age of 70 years, which was due to increased deposition among APOE ε4 carriers. But APOE ε4 status was not associated with hippocampal volume and only affected memory performance from the age of 80 years.

Gender affected the findings, with memory performance poorer and hippocampal volumes smaller among men than women at most ages.

In his editorial, DeCarli says: “While the authors remind us that we cannot infer causality from cross-sectional studies, this remarkable study prompts the question as to what may cause hippocampal and memory changes in early life.”

He notes that factors such as cerebrovascular damage and genetics may play a role, but do not appear to fully explain the observed changes.

“As is often the case for new scientific findings, we are left with more questions than clear answers”, he concludes.

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