One third of patients with pathologically confirmed early-onset Alzheimer’s disease presented with atypical symptoms, and 53% of patients with nonamnestic presentations were initially misdiagnosed, according to a study in the May 17 Neurology. Researchers conducted a retrospective review of clinical data from patients with confirmed early-onset Alzheimer’s disease to determine the frequency and types of incorrect diagnoses. The majority of these cases were diagnosed with other types of dementia, including pseudodementia with depression, semantic dementia, and primary progressive aphasia. “Early-onset Alzheimer’s disease diagnosis often represents a challenge because of the high frequency of atypical presentations,” the study authors wrote. More than one-third (37.5%) of patients presented with atypical symptoms other than memory problems; the most prevalent of these was behavioral/executive dysfunction.
Neuronal activity may be a potential mechanism for vulnerability to amyloid-β deposition in certain areas of the brain, researchers reported in the May 1 online Nature Neuroscience. The investigators examined endogenous neuronal activity in mice with Alzheimer’s disease and determined that this activity regulates the regional concentration of interstitial fluid amyloid-β, which drives local aggregation of amyloid-β. Using unilateral vibrissal stimulation in the contralateral barrel cortex, they found that activity increased interstitial fluid amyloid-β. Unilateral vibrissal deprivation decreased interstitial fluid amyloid-β deposition; long-term deprivation also decreased amyloid plaque formation and growth. “Our results suggest a mechanism to account for the vulnerability of specific brain regions to amyloid-β deposition in Alzheimer’s disease,” the authors concluded.
A newly confirmed genetic risk allele of the clusterin gene contributes to white matter degeneration in young adults and may increase the risk for Alzheimer’s disease later in life, according to results published in the May 4 Journal of Neuroscience. Investigators used diffusion-tensor MRI to scan the brains of 398 healthy young adults (mean age, 23.6) and to evaluate whether the C-allele clusterin risk variant was associated with lower white matter integrity. “Each C-allele copy of the clusterin variant was associated with lower fractional anisotropy—a widely accepted measure of white matter integrity—in multiple brain regions,” the authors wrote. These regions included the splenium of the corpus callosum, the fornix, cingulum, and superior and inferior longitudinal fasciculi in both brain hemispheres. “Young healthy carriers of the clusterin gene risk variant showed a distinct profile of lower white matter integrity that may increase vulnerability to developing Alzheimer’s disease later in life,” the researchers concluded.
A higher BMI may improve survival in patients with amyotrophic lateral sclerosis (ALS). As published in the May 23 online Muscle & Nerve, investigators aimed to determine whether cholesterol levels are an independent predictor of ALS survival. They measured cholesterol levels in 427 people with ALS from three clinical trial databases and found that the low-density and high-density lipoprotein level ratio did not decrease over time, even though BMI significantly declined. “After adjusting for BMI, forced vital capacity, and age, the lipid ratio was not associated with survival,” the investigators wrote. The highest survival rate, though, was found among patients with a BMI between 30 and 35, or mild obesity. “We found that dyslipidemia is not an independent predictor of survival in ALS,” the researchers concluded, whereas, “BMI is an independent prognostic factor for survival after adjusting for markers of disease severity.”
Patients with a history of intracerebral hemorrhage (ICH) should avoid using statins for prevention of ischemic cardiac and cerebrovascular disease, according to a study in the May Archives of Neurology. Statins are widely prescribed for disease prevention, the authors noted, and “although serious adverse effects are uncommon, results from a recent clinical trial suggested increased risk of ICH associated with statin use.” To determine if statin therapy should be avoided in patients with a baseline elevated risk of ICH, investigators evaluated the risks and benefits of the therapy in patients with prior ICH using clinical parameters such as hemorrhage location (deep or lobar). For survivors of ICH both with and without prior cardiovascular events, the benefits of statin therapy were not strong enough to offset the increased risk for hemorrhage recurrence.
Adverse changes in sleep duration are associated with poorer cognitive function in middle-aged adults, per a study in the May 1 Sleep. Researchers conducted cross-sectional studies of women and men (age range, 45 to 69) to examine the effect of changes in sleep duration on cognitive function. Participants’ cognitive function was assessed at baseline, and their sleep duration on an average weeknight was measured once at baseline and again an average of 5.4 years later. After adjustment for age, gender, education, and occupation, the authors reported that “firm evidence remained for an association between an increase from seven or eight hours sleep and lower cognitive function for all tests, except memory, and between a decrease from six or eight hours sleep and poorer reasoning, vocabulary, and Mini-Mental State Examination score.” These adverse changes in duration were equivalent to a four- to seven-year increase in age.