Dementia affects tens of millions worldwide, and Alzheimer’s disease (AD) is the leading cause, defined by amyloid plaques and tau tangles. Because positron emission tomography imaging and cerebrospinal fluid biomarker screening are costly and impractical for broad use, researchers are looking for inexpensive, noninvasive early signals. Neuropsychiatric symptoms—such as depression, anxiety, apathy, agitation, hallucinations, and delusions—can emerge before clear cognitive impairment. This has fueled interest in mild behavioral impairment (MBI), a later-life syndrome of persistent (≥6 months), impactful behavioral change in adults >50 without dementia. MBI is often measured with the MBI Checklist to help identify higher-risk individuals and enrich clinical trial recruitment.

The review examines genetic links between MBI and Alzheimer’s risk, focusing on APOE ε4 and polygenic risk scores (PRS). Evidence suggests APOE ε4 is most consistently associated with affective dysregulation, while links to other MBI domains are less consistent. Some studies suggest domain-specific relationships with dementia risk that vary by APOE status. Exploratory findings connect other AD-related loci—often involving immune/inflammation and synaptic/amyloid-tau pathways—to select MBI domains. In some cohorts, combining MBI phenotyping with PRS may improve early risk stratification. The authors call for larger, longitudinal, multi-ethnic studies that integrate genetics with biomarkers and neuroimaging.

Reference: Angelopoulou E, Koros C, Hatzimanolis A, et al. Exploring the Genetic Landscape of Mild Behavioral Impairment as an Early Marker of Cognitive Decline: An Updated Review Focusing on Alzheimer's Disease. Int J Mol Sci. 2024 Feb 24;25(5):2645. doi: 10.3390/ijms25052645. PMID: 38473892; PMCID: PMC10931648.

This study developed a brief, self-administered home keyboard-tapping battery (TAS Test) to examine whether hand motor performance can detect subtle cognitive differences in cognitively asymptomatic older adults. Community participants age 50+ from the ISLAND Project in Tasmania (June-August 2021) completed a single-key spacebar test (dominant hand, 4 × 10-second blocks) and an alternate-key test (right then left hand, alternating “S” and “;” for 30 seconds each). They also completed online CANTAB cognitive tests in August 2021: Paired Associates Learning (PAL) for episodic memory and Spatial Working Memory (SWM) for working memory/executive planning. Models with standard covariates (age, sex, education, anxiety, depression) were compared to models that added motor features (speed, variability, dwell time, accuracy) using AIC.

In 1,169 cognitively asymptomatic participants, adding motor features improved prediction of episodic memory (PAL errors) beyond demographics and mood. The alternate-key test performed best. The top episodic-memory model included dominant-hand tapping frequency and non-dominant-hand tapping variability. Combining both tapping protocols did not outperform the alternate-key test alone. Tapping features did not consistently improve prediction of working memory (SWM between errors). Only the single-key test modestly improved prediction of the SWM strategy metric. The authors conclude these quick, at-home tapping tasks could support low-cost risk stratification. They call for longitudinal follow-up and comparison with AD biomarkers (e.g., blood tests, PET).

Reference: Wang X, St George RJ, Bindoff AD, et al. Estimating presymptomatic episodic memory impairment using simple hand movement tests: A cross-sectional study of a large sample of older adults. Alzheimers Dement. 2024 Jan;20(1):173-182. doi: 10.1002/alz.13401. Epub 2023 Jul 30. PMID: 37519032; PMCID: PMC10916999.

Alzheimer’s disease (AD) progresses over years from early memory/learning problems to broader cognitive and functional decline. Neuropsychiatric symptoms (NPS)—depression, anxiety, psychosis, agitation/aggression, and apathy—often emerge earlier than once assumed and are linked to faster decline, higher caregiver burden, and greater risk of institutionalization. Diagnosis remains largely clinical despite multiple frameworks, and it’s complicated by normal aging complaints and the need to rule out other medical, neurologic, psychiatric, or medication-related causes. Cognitive screens (e.g., MoCA/MMSE) and DSM-5–based assessment may be supplemented by neuropsych testing and biomarkers/imaging, but NPS can be hard to recognize and attribute to AD versus comorbid illness.

Management prioritizes nonpharmacologic strategies—reassurance/redirection, simplified environments, routines, cognitive stimulation, caregiver support, music/exercise, and cognitive behavioral therapy when feasible—because medication benefits are often modest and risks can be substantial in older adults with dementia. SSRIs/SNRIs are commonly used for depression/anxiety with mixed efficacy, while benzodiazepines and antipsychotics carry important safety concerns and are generally reserved for higher-risk situations (e.g., severe psychosis or agitation). The review notes FDA approval of brexpiprazole for AD-related agitation as a recent development and highlights mixed evidence for apathy treatments (behavioral approaches; variable data for cholinesterase inhibitors and stimulants). Overall, it argues current AD therapies do not reliably treat established NPS and calls for clearer diagnostic standards plus safer, targeted, well-studied interventions.

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Reference: Pless A, Ware D, Saggu S, et al. Understanding neuropsychiatric symptoms in Alzheimer's disease: challenges and advances in diagnosis and treatment. Front Neurosci. 2023 Sep 5;17:1263771. doi: 10.3389/fnins.2023.1263771. PMID: 37732300; PMCID: PMC10508352.