Amyloid variances suggest Alzheimer’s, cerebral small vessel diseases ‘lie on a continuum’

Variances in amyloid positivity across nine subgroups of patients, who were classified according to cognitive states and white matter hyperintensity levels, suggested Alzheimer’s and cerebral small vessel diseases exist on a continuum.

The researchers published the study findings in Neurology.

“Previous studies investigated the prevalence of [amyloid] pathology after dichotomizing patients into groups with either [Alzheimer’s disease] or [subcortical vascular cognitive impairment], and, therefore, failed to cover the whole spectrum of [AD-related cognitive impairment] and [subcortical vascular cognitive impairment], not addressing mixed pathology cases with different levels of [amyloid] and [cerebral small vessel disease] burden,” Sung Hoon Kang, MD, of the department of neurology at Sungkyunkwan University School of Medicine’s Samsung Medical Center in South Korea, and colleagues wrote.

The investigators conducted the current study to assess amyloid positivity frequency among nine groups, composed of 1,047 participants grouped according to a combination of three states of cognition — subjective cognitive decline (n = 294), mild cognitive impairment (n = 237) or dementia (n = 516) — and minimal, moderate or severe levels of white matter hyperintensities (WMH). Further, they sought to evaluate whether certain factors were linked to amyloid after they controlled for WMH and vice versa. All participants had amyloid PET scan data available and were recruited from a single memory clinic in South Korea. Kang and colleagues assessed three parameters: amyloid positivity in the nine groups; the link between amyloid positivity and the severity of WMH; and the independent relationships between clinical and genetic factors and amyloid or WMH.

Findings demonstrated that amyloid positivity increases paralleled cognitive impairment severity increases, which were 15.7% for subjective cognitive decline, 43.5% for mild cognitive impairment and 76.2% for dementia. However, Kang and colleagues also reported decreases in amyloid positivity that coincided with increases in WMH severity, with positivity rates of 54.5% for minimal WMH, 53.9% for moderate WMH and 41% for severe WMH, and increases in the number of lacunes, with positivity rates of 59% for zero, 42% for one to three and 23.4% for three or more. Higher levels of education, the presence of APOE e4 and no diagnosis of diabetes mellitus all exhibited positive associations with amyloid after the researchers controlled for cognitive and WMH status.

“Considering the importance of [amyloid] on cognition, evaluation of [amyloid] biomarkers is warranted in cognitively impaired patients even with severe [cerebral small vessel disease], to help diagnoses, predicting the prognosis and determining the optimal treatment option,” the researchers wrote.