Fortasyn Connect Improves Neuropsychiatric Symptoms in Patients with Mild Cognitive Impairment and Dementia: Results from a Retrospective Real-World Study.

BACKGROUND: Behavioral and psychological symptoms of dementia (BPSD) manifest in the early stages of the disease and impair patients' and caregivers' quality of life. OBJECTIVE: To assess the effectiveness of the nutritional supplement Fortasyn Connect on BPSD for 12 months in people with mild cognitive impairment (MCI) and dementia in clinical practice. METHODS: Retrospective, national, single-center study of 236 patients (158 MCI and 78 dementia; 55.1% of AD etiology). BPSD were assessed with the Neuropsychiatric Inventory (NPI) at month 3, 6, and 12. Cognition (Mini-Mental State Examination, MMSE), depression (Geriatric Depression Scale, GDS), and everyday functioning (Blessed Dementia Scale, BLS-D; Rapid Disability Rating Scale 2, RDRS2) were also evaluated. RESULTS: Total NPI score, caregiver impact, and symptoms of depression, anxiety, apathy, and irritability improved after 3, 6, and 12 months from Fortasyn Connect initiation (p < 0.001). NPI decreases were more pronounced when baseline NPI score was higher than > 20 points (p < 0.001). The benefit was independent of gender, age, diagnosis, etiology, or concomitant treatment (p < 0.0001), although larger decreases in NPI total score were observed in MCI patients (p < 0.0001). After 12 months, GDS scores decreased (p = 0.042), and MMSE, BLS-D, and RDRS 2 scores remained stable. CONCLUSION: Fortasyn Connect improved BPSD over at least a year in patients with MCI and dementia. Depression, anxiety, apathy, and irritability were the symptoms that improved the most. The benefit was independent of patients' characteristics and treatment but was greater if prescribed early and when baseline NPI scores were higher.

Damage of the temporal lobe and APOE status determine neural compensation in mild cognitive impairment.

In mild cognitive impairment (MCI), the APOE4 genotype is associated with accelerated memory decline, likely due to the impact of neuropathology on main cerebral networks required for successful memory retrieval and/or to decreased capacity for recruiting secondary networks that might compensate for that brain damage. Here, we tested this hypothesis in twenty-six healthy older adults and thirty-four MCI patients, of which sixteen were APOE4 carriers. Compared to controls, MCI showed hippocampal volume reduction, cortical thinning in frontal, temporal and parietal regions, and dysfunctional EEG oscillations across fronto-temporal networks. But importantly, APOE4 status was the critical factor in determining the impact of temporal lobe degeneration on memory in MCI individuals. Specifically, path analyses revealed that hippocampal damage in MCI was responsible for memory deterioration in APOE4 carriers, a relationship mediated by the serial intervention of three related factors in noncarriers. Temporal cortical thickness (first mediator) accounted for activation of functional networks through synchronized theta activity across temporal regions (second mediator), which, in turn, coordinated memory reactivation through desynchronized alpha/beta activity across sensorimotor areas (third mediator). Results revealed that, contrary to APOE4-carrier patients, noncarriers are successful in recruiting secondary cortical networks to improve memory performance as long as the integrity and functionality of the temporal lobe is preserved, a fact primarily dependent on hippocampal degeneration.

Memory inhibition as a critical factor preventing creative problem solving.

The hypothesis that reduced accessibility to relevant information can negatively affect problem solving in a remote associate test (RAT) was tested by using, immediately before the RAT, a retrieval practice procedure to hinder access to target solutions. The results of 2 experiments clearly showed that, relative to baseline, target words that had been competitors during selective retrieval were much less likely to be provided as solutions in the RAT, demonstrating that performance in the problem-solving task was strongly influenced by the predetermined accessibility status of the solutions in memory. Importantly, this was so even when participants were unaware of the relationship between the memory and the problem-solving procedures in the experiments. This finding is consistent with an inhibitory account of retrieval-induced forgetting effects and, more generally, constitutes support for the idea that the activation status of mental representations originating in a given task (e.g., episodic memory) can unwittingly have significant consequences for a different, unrelated task (e.g., problem solving). (PsycINFO Database Record

Atrophy of amygdala and abnormal memory-related alpha oscillations over posterior cingulate predict conversion to Alzheimer's disease.

Synaptic dysfunction, a key pathophysiological hallmark of Alzheimer's disease (AD), may account for abnormal memory-related EEG patterns in prodromal AD. Here, we investigate to what extent oscillatory EEG changes during memory encoding and/or retrieval enhance the accuracy of medial temporal lobe (MTL) atrophy in predicting conversion from amnestic mild cognitive impairment (aMCI) to AD. As expected, aMCI individuals that, within a 2-year follow-up period, developed dementia (N = 16) compared to healthy older (HO) (N = 26) and stable aMCI (N = 18) showed poorer associative memory, greater MTL atrophy, and lower capacity to recruit alpha oscillatory cortical networks. Interestingly, encoding-induced abnormal alpha desynchronized activity over the posterior cingulate cortex (PCC) at baseline showed significantly higher accuracy in predicting AD than the magnitude of amygdala atrophy. Nevertheless, the best accuracy was obtained when the two markers were fitted into the model (sensitivity = 78%, specificity = 82%). These results support the idea that synaptic integrity/function in the PCC is affected during prodromal AD and has the potential of improving early detection when combined with MRI biomarkers.

APOE ɛ4 constrains engagement of encoding-related compensatory networks in amnestic mild cognitive impairment.

People with amnestic mild cognitive impairment (aMCI), compared to healthy older adults (HO), benefit less from semantic congruent cues during episodic encoding. The presence of the apolipoprotein E (APOE) ɛ4 makes this congruency benefit smaller, but the neural correlates of this deficit are unknown. Here, we estimated the source generators of EEG oscillatory activity associated with successful encoding of face-location associations preceded by semantically congruent and incongruent cues in HO (N = 26) and aMCI subjects (N = 34), 16 of which were ɛ4 carriers (ɛ4(+) ) and 18 ɛ4 noncarriers (ɛ4(-) ). Source estimation was performed in those spectrotemporal windows where the power of low-alpha, high-alpha, and beta oscillatory activity differed either between congruent and incongruent faces or between groups. Differences in high-alpha and beta-oscillatory dynamics indicated that aMCI ɛ4(+) are unable to activate lateral regions of the temporal lobe involved in associative memory and congruency benefit in HO. Interestingly, and regardless of APOE genotype, aMCI activated additional regions relative to HO, through alpha oscillations. However, only activation in a distributed fronto-temporo-parietal network in ɛ4 noncarriers was paralleled by enhanced memory. On the contrary, the redundant prefrontal activation shown by aMCI ɛ4(+) did not prevent performance from decreasing. These results indicate that the effect of aMCI-related degeneracy on functional networks is constrained by the presence of APOE ɛ4. Whereas individuals with aMCI ɛ4(-) activate attentional, perceptual and semantic compensatory networks, aMCI ɛ4(+) show reduced processing efficiency and capacity.