Introduction: Intraindividual variability (IIV) in motor performance has been shown to predict future cognitive decline. The apolipoprotein E-epsilon 4 (APOE-ε4) allele is also a well-established risk factor for memory decline. Here, we present novel findings examining the influence of the APOE-ε4 allele on the performance of asymptomatic healthy elders in comparison to individuals with amnestic MCI (aMCI) on a fine motor synchronization, paced finger-tapping task (PFTT).
Method: Two Alzheimer's disease (AD) risk groups, individuals with aMCI (n = 24) and cognitively intact APOE-ε4 carriers (n = 41), and a control group consisting of cognitively intact APOE-ε4 noncarriers (n = 65) completed the Rey Auditory Verbal Learning Test and the PFTT, which requires index finger tapping in synchrony with a visual stimulus (interstimulus interval = 333 ms).
Results: Motor timing IIV, as reflected by the standard deviation of the intertap interval (ITI), was greater in the aMCI group than in the two groups of cognitively intact elders; in contrast, all three groups had statistically equivalent mean ITI. No significant IIV differences were observed between the asymptomatic APOE-ε4 carriers and noncarriers. Poorer episodic memory performance was associated with greater IIV, particularly in the aMCI group.
Conclusions: Results suggest that increased IIV on a fine motor synchronization task is apparent in aMCI. This IIV measure was not sensitive in discriminating older asymptomatic individuals at genetic risk for AD from those without such a genetic risk. In contrast, episodic memory performance, a well-established predictor of cognitive decline in preclinical AD, was able to distinguish between the two cognitively intact groups based on genetic risk.
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http://dx.doi.org/10.1080/13803395.2016.1273321 | DOI Listing |
Alzheimers Dement
December 2024
Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA.
Background: Sleep dysfunction is commonly seen in Alzheimer's disease (AD) and Progressive Supranuclear Palsy (PSP), potentially worsening these conditions. Investigating early neuropathological changes in human sleep-promoting neurons, which often precede cognitive decline, is crucial for understanding the basis for sleep dysfunction as possible treatments yet remain underexplored. We used postmortem brains of AD and PSP patients to quantify neuronal numbers and tau burden in the intermediate nucleus of the hypothalamus (IntN), VLPO analog, known for its role in sleep maintenance.
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December 2024
Physiopathology in Aging Laboratory (LIM-22), University of São Paulo Medical School, São Paulo, São Paulo, Brazil.
Background: Excessive daytime sleepiness is a common and early symptom of Alzheimer's disease (AD). The subcortical wake-promoting neurons in the lateral hypothalamic area, tuberomammillary nucleus (TMN), and locus coeruleus synchronize to maintain wakefulness/arousal. Although significant neuronal decline occurs in wake-promoting regions, the TMN histaminergic neurons remain relatively more intact than orexinergic and nor-adrenergic neurons.
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December 2024
University of Guadalajara, Guadalajara, JA, Mexico.
Background: The ways in which diverse genetic variants interact to affect the phenotype of AD is poorly understood. The relatively consistent phenotype associated with specific mutations causing autosomal dominant AD (ADAD) provides the opportunity to study how other genetic variants contribute to disease manifestations.
Method: We performed an in-depth case study of a patient with the A431E PSEN1 mutation who had onset of progressive spastic paraplegia at age 20.
Alzheimers Dement
December 2024
Texas Tech University Health and Sciences Center El Paso, El Paso, TX, USA.
Background: Mitochondria plays a crucial role at synapses in providing synaptic energy, healthy synaptic function, and cognitive functions. Amyloid-beta and phosphorylated tau protein oligomers cause severe mitochondrial defects in Alzheimer's disease (AD), which leads to the lack of synaptic energy and impaired synapse functions in AD. MicroRNAs (miRNAs) present within the mitochondria are involved in multiple mitochondrial activities and mitochondrial function.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Texas Tech University Health Sciences Center, Lubbock, TX, USA.
Background: Disrupted balance between amyloidogenic and non-amyloidogenic pathways leads to cognitive decline in Alzheimer's disease (AD). Evidence suggests vitamin A (VA) supplementation favors the non-amyloidogenic pathway through upregulation of α-secretase. Originally used to map embryonic retinoic acid (RA) signaling, RARE-LacZ mice possess multiple LacZ genes controlled by retinoic acid response elements (RAREs).
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