Highlights in Alzheimer’s disease research from AAN Virtual 2022

Age-related risk factors and updated prevalence estimates

Vascular risk factors for dementia vary with age suggesting the need for age-specific dementia risk scores. McGrath and colleagues¹ studied which risk factors should be prioritised at particular ages using Framingham Heart Study data. At age 55 the most important factors were systolic blood pressure and diabetes mellitus (DM), at age 65 non-stroke cardiovascular disease, at ages 70 and 75 DM and stroke, and at age 80 DM, stroke and antihypertensive use (protective).

Need for age-specific dementia risk scores

Gillis et al.² have updated United States (US) prevalence estimates for Alzheimer’s disease (AD) taking into account racial/ethnic diversity. They used data from a variety of sources including the Centers for Disease control and Prevention Wonder 2021 database. Updated estimates for mild cognitive impairment (MCI) due to AD (amyloid beta positive) were 6.9 million for ages ≥50 years (5.7%) and 5.7 million for ages ≥65 years (9.8%). For mild AD dementia the figures were 2.5 million for both ages ≥50 years (2.1%) and ≥65 years (4.2%). These estimates are higher than those derived using pre-2021 publications. The authors suggest this is due to previously under-represented populations and will be important to consider in future clinical trial design and recruitment.

Estimates are higher due to previously under-represented populations

Additive effect of aging and plasma biomarkers

Aging is the main risk factor for most neurodegenerative diseases. Cividini and colleagues³ used MRI imaging to look at changes in cortical thinning across the lifespan in healthy brains to help understand the additive effect that aging may have in these diseases. Decreased thickness was seen in 97% of cortical regions with advancing age, with highest cortical thinning in the temporal, frontal and parietal lobes and insular cortex, and least in the occipital lobe. They concluded that observing the trajectories of normal brain aging helps to identify those areas that might be more vulnerable to neurodegeneration.

Identify cortical areas more vulnerable to neurodegeneration

A combination of plasma neurodegenerative and inflammatory cytokine biomarkers to identify AD patients was the proposal from Chenna et al.,⁴ who compared a range of nervous system proteins in plasma from 72 AD patients (mild, moderate and severe) to 64 healthy controls. There were significant increases in median levels of NF-L, t-Tau, p-Tau181, IL-6, IL-10, and TNFα in the combined AD group relative to controls (p<0.0001). 

A combination of plasma biomarkers to identify AD patients

CSF testing, quality of life and COVID-19-related mental health

Krivanek and Gale⁵ looked at clinical practice prior to published appropriate use criteria (AUC) for cerebrospinal fluid (CSF) biomarker testing in AD diagnosis. Clinical data was available for 105 patients in a tertiary care dementia clinic, who would all have met AUC, with the most common (53.3%) criteria ‘MCI or dementia with onset before age 65’. In 48.5% of cases the results of CSF testing led to a change in initial diagnosis. The least stable diagnoses were ‘dementia’, ‘neurodegenerative process’, and ‘cognitive impairment of unknown aetiology’, and the most stable was ‘AD’.

In 48.5% of cases the results of CSF testing led to a change in initial diagnosis

Villarejo-Galende and colleagues⁶ assessed patients’ experience of living with early AD using a range of patient-reported outcomes. Their study included 149 patients with mild or prodromal AD and mean disease duration 1.3±1.7 years. 22% of patients reported depressive symptoms and 94% mild-to-moderate hopelessness. The Quality of Life in AD Scale (QoL-AD) scores were positively correlated with GSES scores and negatively correlated with BDI-FS, SSCI-8, RADIX practical and emotional consequences, and BHS scores. Better understanding the patient’s perspective could facilitate implementing individualized supportive strategies to improve QoL.

Understanding the patient’s perspective could facilitate individualized strategies to improve QoL

Finally, Kim et al.⁷ reported on the impact of the COVID-19 crisis on the mental health of dementia patients. In 2021 they conducted a telephone survey of 2080 patients registered as having dementia with a response from 1038 caregivers. The study asked which, if any, neuropsychiatric symptoms had been aggravated by the recent pandemic. At least one aggravating symptom was experienced by 26.4% of patients, predominantly depression/dysphoria (44.5%), sleep disturbance (9.5%) and delusions (9.1%). A more preemptive strategy to manage such symptoms would help both patients and caregivers.

At least one aggravating neuropsychiatric symptom was experienced by 26.4% of patients