Abstract
BackgroundWe examined interactive effects of sex, diagnosis, and cerebrospinal fluid (CSF) amyloid beta/phosphorylated tau ratio (Aβ/P-tau) on verbal memory and hippocampal volumes.MethodsWe assessed 682 participants (350 women) from BioFINDER (250 cognitively normal [CN]; and 432 symptomatic: 186 subjective cognitive decline [SCD], 246 mild cognitive impairment [MCI]). General linear models evaluated effects of Alzheimer’s disease (AD) proteinopathy (CSF Aß/p-tau ratio), diagnosis, and sex on verbal memory (ADAS-cog 10-word recall), semantic fluency (animal naming fluency), visuospatial skills (cube copy), processing speed/attention functions (Symbol Digit Modalities Test and Trail Making Part A), and hippocampal volumes.ResultsAmyloid-positive (Aβ/P-tau+) CN women (women with preclinical AD) showed memory equivalent to amyloid-negative (Aβ/P-tau−) CN women. In contrast, Aβ/P-tau+ CN men (men with preclinical AD) showed poorer memory than Aβ/P-tau− CN men. Symptomatic groups showed no sex differences in effect of AD proteinopathy on memory. There was no interactive effect of sex, diagnosis, and Aβ/P-tau on other measures of cognition or on hippocampal volume.ConclusionsCN women show relatively preserved verbal memory, but not general cognitive reserve or preserved hippocampal volume in the presence of Aβ/P-tau+. Results have implications for diagnosing AD in women, and for clinical trials.
Highlights
We examined interactive effects of sex, diagnosis, and cerebrospinal fluid (CSF) amyloid beta/phosphorylated tau ratio (Aβ/P-tau) on verbal memory and hippocampal volumes
The patients with cognitive symptoms (“symptomatic patients”) had all been referred to one of three participating memory clinics in the south of Sweden, mostly from primary care, and consecutively enrolled in BioFINDER based on the following inclusion and exclusion criteria: (1) perceived cognitive decline, (2) did not fulfill Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) [22] criteria for Major Neurocognitive Disorder, as assessed by a memory clinic physician, (3) had a Mini-Mental State Examination (MMSE) score of 24 to 30 points, (4) were aged 60 to 80 years, and (5) were fluent in Swedish
The current study showed that women with Alzheimer’s disease (AD) proteinopathy (Aβ/P-tau+) showed no memory impairment relative to Amyloid beta (Aβ)/P-tau− women prior to self-reporting concerns about their cognition
Summary
We examined interactive effects of sex, diagnosis, and cerebrospinal fluid (CSF) amyloid beta/phosphorylated tau ratio (Aβ/P-tau) on verbal memory and hippocampal volumes. Women have verbal memory strengths that appear to be sustained early in the disease, despite measurable pathological changes, including fluorodeoxyglucose positron emission tomography (FDG PET) abnormalities [1], hippocampal volume (HV) loss [2], and amyloid beta (Aβ) protein accumulation as shown by a positive amyloid PET scan [3, 4]. This early preserved memory may delay diagnosis [5], which is Memory advantages in women throughout the lifespan could relate to a variety of etiological factors (e.g., [9, 11,12,13,14]).
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