Early-onset Alzheimer’s Disease (EOAD) affects patients younger than age 65 and may present with non-amnestic features. Black adults are up to twice as likely as White adults to develop Alzheimer disease (AD) (1, 2). In addition, studies suggest that Black patients with dementia not only experience greater delays to diagnosis but they are often undertreated, which may reflect disparities in access to healthcare, relative lack of AD awareness, and systemic distrust (3–6). Whereas ethnoracial disparities have been reported for typical late-onset Alzheimer’s Disease (LOAD), there is a relative paucity of similar studies for diverse patients with EOAD.

Most studies on atypical presentations of AD, including EOAD, focus on white populations (7, 8) Compared to typical AD, little is known about the differences in pathogenesis, genetic diagnostic biomarker profile, and natural history, particularly among Black patients (9). Interestingly, Black and Latino AD patients may have longer survival compared with white AD patients (10). Clinically, Black participants with dementia may have higher neuropsychiatric symptoms/severity and functional dependence as compared to White patients with dementia (11). Studies suggest that the underlying pathogenesis of cognitive impairment in AD may be different in Black patients compared to White patients (12). Despite disproportionately higher rates of AD among people wo identify as Black, a recent studies found lower odds of amyloid PET positivity among Black and Hispanic patients compared with White patients (13, 14).

Only one study specifically characterized biomarker differences between ethnicities, finding that Black patients had lower levels of total and phosphorylated tau (t-tau and p-tau), and amyloid-beta (Ab) levels in their cerebrospinal fluid (CSF) when compared with non-Hispanic White people (15). Another study also found lower levels of CSF t-tau and p-tau among Black patients, though it was found to be perhaps a function of ApoE4 status (16).

Pathologically, Black patients with AD are more likely to have mixed pathology than White patients with AD, which may at least partially account for the variability in biomarkers (17). Further study of biomarker and clinicodemographic data may be the key to providing culturally competent care for Black patients with AD.

As a tertiary care center with a large Black population on the South Side of Chicago, we sought to compare several aspects of the utilization of medical services by patients, the perceived clinical features of the disease at presentation, diagnostic testing, and clinical features of disease among Black and White patients diagnosed with EOAD. We also aimed to identify differences in diagnostic tests ordered and obtained to help inform and identity potential barriers in diagnosis in the Black EOAD population.

The study was reviewed and approved by the Institutional Review Board of the affiliated academic medical center.

In our cohort, Black patients with EOAD were, on average, more advanced, and experienced a longer time to diagnosis than their White counterparts. Non-amnestic, atypical presentations were more common in White patients presenting with EOAD, at least in our sample. We also found that Black patients not only completed fewer diagnostic tests that were ordered (specifically CSF testing, FDG-PET imaging, and neuropsychological testing), but as a group, CSF testing and neuropsychological assessments were ordered less frequently in Black patients compared with White patients.

It is important to acknowledge that in our study, Black patients on average experienced a longer period between symptom onset and diagnosis. A 2012 study in a large, Dutch cohort (n = 414) found that EOAD patients took an average of 1.6 years longer than LOAD patients to obtain a diagnosis (20). Prolonged time from symptom onset to diagnosis could be due to a number of factors. Atypical, non-amnestic presentation of AD in patients less than 65 years old may be more likely to be misdiagnosed or missed by clinicians.

We also found that Black patients in our cohort trended towards lower scores on the MoCA at presentation. Although this did not reach statistical significance, some of the individual tasks, such as abstractions and delayed recall, did. Does a lower MoCA score in this context necessarily imply greater cognitive impairment? Prior evidence has suggested that older Black participants tend to perform worse on tests of executive function and visuospatial ability, when compared with older White participants, even when controlling for education (21–25).

It is not known whether this finding is also observed in Black patients less than 65 years of age. Interestingly, one of the earliest studies of normative performance on the MoCA in Black participants (1,419 patients with a mean age 49 years) found that total MoCA scores were lower than normative data derived from elderly White participants (26). In the same study, Rossetti et al. (26) found that some domains were especially missed by a large portion of the sample—including delayed free recall and abstraction—as in our cohort. This may suggest that certain items in MoCA have lower psychometric utility for Black participants.

One study using a related cognitive measure, the Mini Mental Status Exam (MMSE), demonstrated a lower score at presentation in Black and Latino patients with AD as compared to White patients with AD, but no appreciable difference among Black and Non-Hispanic White cognitively normal participants (27). The role of cognitive reserve in racially diverse populations also remains unclear. One study found that Black patients have a lower baseline level of cognition but progress more slowly over time; however, additional studies are necessary for further characterization (28).

Lower mean scores specifically in delayed free recall and abstraction items among Black patients are also consistent with our overall finding that amnestic presentations were more common among Black EOAD patients than their White counterparts. This is contrary to our current understanding that atypical, non-amnestic presentations of AD are more characteristic in EOAD cohorts (29). What may account for this difference? This may represent an overall selection bias among our clinic population.

For example, it could be that patients are more likely to present to a memory clinic for symptoms such as forgetfulness than visual difficulties due to wider awareness of the former symptom as a neurological problem. A 2023 study of 4,284 patients from 2008 to 2018 has shown that Black patients who present to memory clinic are more likely to have moderate or severe dementia at their initial visit (30).

Perhaps the most evident disparity was in access to EOAD care, as Black patients completed fewer diagnostic tests than White patients, suggesting additional social determinants of health must be explored in order to further characterize this gap. Providers also ordered relatively lower numbers of lumbar puncture procedures for Black patients by providers, presuming that the provider did not order the study because the patient declined. Lumbar puncture (LP) for CSF testing is one of the most crucial components of EOAD diagnosis, especially when accounting for financial and insurance barriers to care. Existing research has shown, consistent with our study, that Black patients are less likely than White patients to agree to a lumbar puncture (31). A general culture of medical mistrust and the historical context of medical researchers exploiting diverse patients are some of the many reasons patients and their caregivers may be less inclined to agree to an invasive test (32). Further research is needed to determine whether access to non-invasive diagnostic tests such as amyloid PET scans may mitigate diagnostic disparities in EOAD care.

It is also interesting to note that neuropsychological testing was less likely to be completed by Black patients in our cohort. We also find that providers were less likely to order neuropsychological testing for Black patients. Many factors may have contributed to this finding, such insurance barriers, access to transportation or caregiver constraints. Testing itself also takes upwards of 6 h, incurring an additional transportation or time burden for patients that may need transport or work full-time. Coverage for testing is variable for EOAD patients who are younger than 65 years of age. For example, the FDG-PET is not covered by Medicare for EOAD patients, which may partially explain the low completion rate. Provider bias of a patient’s general willingness to pursue such studies may also play a role in the discrepancy between Black and White patients. Further exploration of such barriers is imperative to ensure that the healthcare system is able to deliver uniformly culturally competent care and that all patients have access to early diagnosis and a comprehensive list of treatment options, particularly in the new era of disease-modifying anti-amyloid therapies.

These disparities in care highlight the value of culturally competent and ethnically informed memory care providers in an increasingly demanding medical field. Such awareness is imperative to mitigate rather than exacerbate existing ethnoracial disparities in AD diagnosis and treatment as well as clinical trial enrollment.