Sensory changes in preclinical, prodromal, and clinical Alzheimer's disease and related dementias

This special issue highlights emerging research on sensory changes in the context of Alzheimer's disease (AD) and related dementias (ADRD). Sensory changes in hearing, vision, olfaction, and other senses are common in aging. ¹ Prior studies have found consistent associations of sensory deficits (individual and multiple senses) with cognitive decline and dementia. ² Changes in peripheral sensory structures, such as the retina, or sensory processing regions in the brain also may co‐occur with ADRD‐related neurodegeneration. ² There is increasing excitement that sensory changes could be clinical predictors or biomarkers for ADRD. Novel and easily assessed biomarkers for ADRD are lacking, and sensory changes can be clinically detectable without invasive procedures. There is also emerging evidence that sensory impairments, especially in hearing or vision, could be potential risk factors for dementia. ³ , ⁴ This special issue brings together a series of original research papers on sensory changes in ADRD, with a special interest in sensory changes as predictors of cognitive decline and dementia including as novel biomarkers for ADRD. Articles span sensory domains, including studies on hearing, visual and ocular measures, and olfaction, as well as integration of multiple senses. Further, the articles in this special issue report associations and prediction of multiple ADRD outcomes including cognitive decline, clinical ADRD outcomes, neuroimaging, and blood‐based biomarkers.

We start the special issue with a paper by Xiao et al. ⁵ that evaluated associations of olfactory dysfunction and neurofilament light chain (NfL) with cognitive decline in the Shanghai Aging Study. Participants with combined poor olfaction and high NfL showed the highest risk of cognitive decline, suggesting that olfactory dysfunction in combination with NfL concentration, may be able to identify individuals at risk for accelerated cognitive decline. ⁵ Next the issue includes two papers that evaluate whether adding multiple sensory (olfaction, hearing, and vision) and motor measures can improve prediction of ADRD outcomes. Schubert et al. ⁶ found that adding sensory (olfaction, hearing, and vision) and motor measures assessed in midlife to two established risk prediction algorithms significantly improved areas under the curve for the prediction of 10‐year cognitive decline and impairment. ⁶ Paulsen et al. ⁷ showed that sensory and motor function measures also improved risk predictions of biomarker positivity of serum‐based NfL but not amyloid beta (Aβ)42/Aβ40.

Next, the special issue focuses on several papers related to hearing loss. Stevenson‐Hoare et al. ⁸ found cross‐sectional associations of pure tone audiometry and cognition and that self‐reported hearing loss was associated with worse cognition and higher risk of dementia over 17 years in a German cohort study. Participants with both hearing and short‐term memory problems showed the highest risk of dementia over follow‐up. ⁸ Fitzhugh and Pa ⁹ evaluated sex differences in the association among hearing loss, dementia, and brain atrophy. Women with poor hearing had higher risk of dementia and greater atrophy of auditory and limbic regions on brain magnetic resonance imaging (MRI), whereas men with poor hearing did not have increased risk for dementia or brain differences compared to normal hearing. Agrawal et al. ¹⁰ examined hearing, cognitive function, and neuroimaging differences in an urban Indian cohort aged ≥ 45 years. Audiometric hearing loss was associated with a 69% higher likelihood of cognitive impairment and lower gray matter volume in the medial temporal lobe. ¹⁰

The remaining articles evaluate novel sensory biomarkers for dementia detection. Medel et al. ¹¹ evaluate distortion product otoacoustic emissions (DPOAEs), which are sounds emitted by normal cochlear hair cells. They found that DPOAEs—and not conventional audiometry—was associated with dementia staging classification and brain atrophy in a group with mild hearing loss and normal hearing. ¹¹ Gibbon et al. tested associations between retinal measures (optic disc pallor, peripapillary retinal nerve fiber layer thickness) and MRI markers of cerebral small vessel disease (e.g., lacunes, microbleeds, white matter hyperintensities, and enlarged perivascular spaces). Optic disc pallor was associated with enlarged perivascular spaces in basal ganglia. ¹² Gramkow et al. ¹³ evaluated the diagnostic performance of hand‐held, quantitative light reflex pupillometry (qLRP) and found that qLPR was able to discriminate AD from other dementias and cognitively normal participants. Chua et al. ¹⁴ developed a deep‐learning algorithm using multiple measures from optical coherence tomography (OCT) to detect AD and mild cognitive impairment (MCI). The combined algorithm outperformed single OCT parameters for discriminating cognitive impairment in both Asian and White participants. ¹⁴ Finally, Opwonya et al. found that MCI patients showed altered pupillary response patterns during cognitive task performance (e.g., task‐evoked pupillary response) compared to cognitively normal South Korean older adults, highlighting the potential of oculomotor changes as a biomarker for early cognitive decline. ¹⁵

Overall, the papers in this special issue highlight novel findings on the link between sensory loss and dementia outcomes, as well as the potential role of sensory changes in prediction and detection of ADRD. This work suggests that prediction models for dementia would benefit from the inclusion of sensory impairment measures, that associations are consistent cross‐nationally but may differ by sex, and identifies novel sensory measures that could be diagnostic indictors for ADRD.

CONFLICT OF INTEREST STATEMENT

The authors declare no conflicts of interest. Author disclosures are available in the Supporting Information.

Supporting information

Supporting Information