Alzheimer’s disease pathology was common in people diagnosed with other dementias, a large cross-sectional study in Sweden showed.

While most patients clinically diagnosed with Alzheimer’s had evidence of cerebrospinal fluid (CSF) amyloid and tau pathology, those biomarkers also emerged in people with other dementias, said Tobias Borgh Skillbäck, MD, PhD, of Sahlgrenska University Hospital in Molndal, Sweden, and co-authors.

In nearly 14,000 adults, a clear, Alzheimer’s-like profile based on three CSF biomarkers — amyloid-beta 1-42, total tau (t-tau), and phosphorylated tau 181 (p-tau181) measurements — was seen in 68% of people with early-onset Alzheimer’s disease, 65% of late-onset Alzheimer’s, and 52% of people with mixed Alzheimer’s and vascular dementia.

Among people without an Alzheimer’s diagnosis, the Alzheimer’s profile emerged in 25% of people with unspecified dementia, 9% of people with Parkinson’s disease dementia, and 8% of people with frontotemporal dementia, Skillbäck and colleagues wrote in JAMA Neurology.

In several dementias, scores on the Mini-Mental State Examination (MMSE) were associated with CSF biomarkers.

MMSE scores were linked with amyloid-beta 1-42 in late-onset Alzheimer’s, vascular dementia, frontotemporal dementia, and unspecified dementia. MMSE scores also were tied to t-tau in late-onset Alzheimer’s, early-onset Alzheimer’s, and unspecified dementia; and linked with p-tau181 in early-onset Alzheimer’s disease.

The findings confirm that “concomitant amyloid-beta and tau pathology is common in other dementias,” Skillbäck said. “This is important looking forward, as new disease-modifying treatments of Alzheimer’s might also benefit patients presenting with other clinical dementias,” he told MedPage Today.

Alzheimer’s disease pathology has been identified in multiple dementia types over the years. Most recently, an autopsy study detected amyloid plaques and tau tangles in several clinical syndromes, including those not typically associated with Alzheimer’s disease, like frontotemporal dementia.

The Swedish study merged archived CSF measurements made in clinical practice at the Sahlgrenska University Hospital with data from the SveDem national registry of people with dementia disorders from October 2010 through August 2022.

Participants had a dementia diagnosis and a complete set of amyloid-beta 1-42, t-tau, and p-tau181 measurements registered less than 3 years after their diagnosis date. A median of 9 weeks elapsed between diagnosis and sampling.

The researchers defined CSF values as pathological or normal by harmonizing reference values. Measurements below the reference value for amyloid-beta 1-42, and above the reference values for t-tau and p-tau181, were considered pathological.

The cohort included 13,882 dementia patients; 53% were female and the median age was 74.

People with Alzheimer’s disease had low concentrations of amyloid-beta in CSF and high concentrations of t-tau and p-tau 181, as expected.

“However, we also identified large shares of patients who were CSF amyloid- and tau-positive in the clinically diagnosed groups with non-Alzheimer’s dementia, including Parkinson’s disease dementia, dementia with Lewy bodies, frontotemporal dementia, vascular dementia, and other dementias, as well as in unspecified dementia, even though a large majority of patients received their diagnosis in specialist care (85%) and after CSF testing (88%),” Skillbäck and co-authors observed.

CSF biomarker data and diagnosis information were drawn from clinical practice — after CSF testing in the majority of cases — so it’s not surprising that most patients in the Alzheimer’s diagnosis groups had an Alzheimer’s-like biomarker profile, the researchers noted.

“The obvious risk of circular reasoning precludes further conclusions from being drawn from this finding,” Skillbäck and colleagues wrote. “However, this would not negatively influence the conclusions of this study, as a main point is that amyloid pathology is common in other dementias as well.”

The study also was limited by using MMSE scores as a proxy measurement for cognitive function, they added.

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