Neuropsychiatric Symptoms Differ in Early- vs Late-Onset Alzheimer Disease

Early-onset (EO) Alzheimer disease (AD) is associated with higher elation and appetite-related neuropsychiatric symptoms but fewer nighttime behaviors relative to late-onset (LO) AD. These study findings were published in Alzheimer’s & Dementia.

Previous studies have reported that EOAD is associated with a greater burden of neuropsychiatric symptoms, steeper declines in cognitive deficits, and faster accumulation of AD pathology. However, age differences between individuals with EOAD and LOAD make it difficult to determine if neuropsychiatric symptoms are due to age or underlying disease-related pathology.

To elucidate this issue, investigators from Indiana University School of Medicine conducted a cross-sectional study to compare the burden of neuropsychiatric symptoms between EO and LO AD, using data from the Uniform Data Set (UDS) – an ongoing standardized data collection protocol from the National Alzheimer’s Coordinating Center (NACC). Patients with mild cognitive impairment (MCI) or dementia due to probable AD between 2005 and 2021 were evaluated for neuropsychiatric symptoms on the basis of age at AD onset. A group of cognitively unimpaired individuals were used as a comparator group. Neuropsychiatric symptoms were assessed using the Neuropsychiatric Inventory Questionnaire (NPI-Q).

The investigators included 2940 patients with EOAD (56.7% women; 86.0% White; mean age=62.4 years; SD, 5.9), 2433 EOAD comparators (69.6% women; 77.1% White; mean age=58.2; SD, 4.8), 8665 patients with LOAD (67.6% women; 58.2% White; mean age=78.9; SD, 6.6), and 6342 LOAD comparators (82.3% women; 78.5% White; mean age=73.5; SD, 6.5). The mean neuropsychiatric symptom burden was significantly higher in both the EOAD (3.1) and LOAD (2.5) groups relative to the comparator groups (0.5 and 0.4, respectively).

When stratified by the 12 neuropsychiatric symptom categories, the investigators found that the patients with EOAD had a higher burden of elation or euphoria (adjusted odds ratio [aOR], 3.41; 95% CI, 1.39-8.33; P =.0072) and appetite or eating problems (aOR, 1.36; 95% CI. 1.04-1.78; P =.0224) but lower rates of nighttime behaviors (aOR, 0.77; 95% CI, 0.64-0.93; P =.0075) than the LOAD group relative to their respective control cohorts.

The severity of neuropsychiatric symptoms was similar between the EOAD and LOAD groups relative to their control cohorts, except that the severity of nighttime behaviors was lower in EOAD than LOAD (aOR, 0.55; 95% CI, 0.38-0.81; P =.0021).

Among only patients with AD-dementia, EOAD was associated with a higher prevalence of elation or euphoria (aOR, 3.41; 95% CI, 1.39-8.37; P =.0074) and lower prevalence of nighttime behaviors (aOR, 0.70; 95% CI, 0.58-0.86; P =.0006) compared with LOAD relative to their control cohorts. The difference in the severity of nighttime behaviors remained consistent with the pooled analysis (aOR, 0.57; 95% CI, 0.38-0.83; P =.0041).

Among only patients with MCI, no group differences in the prevalence of neuropsychiatric symptoms were observed, but the difference in the severity of nighttime behaviors was consistent (aOR, 0.46; 95% CI, 0.28-0.76; P =.0027).

The results of this study replicate previous study findings that indicate EOAD is associated with a higher burden of neuropsychiatric symptoms, relative to LOAD. However, “When accounting for the tendency for [neuropsychiatric symptoms] to be more prominent in younger than older adults (ie, age effects), we found only elation, eating behaviors, and nighttime behaviors were disease-specific,” the investigators concluded.

These study findings may be limited, as the investigators did not correct for multiple comparisons.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

This article originally appeared on Psychiatry Advisor