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The apathy, gait impairment, and executive dysfunction (AGED) triad vascular variant.

ABSTRACT: Apathy, gait disturbances, and executive dysfunction (AGED) often occur together. Although they can arise independently, the presence of one might portend another. This recognition suggests the possible etiology. We focus on the most common, the vascular. We explain the AGED vascular mechanism through the ambibaric brain concept. The brain contains two complementary blood pressure systems: One high in the primitive brain (brainstem, basal ganglia, and thalamus) and a low-pressure system in the Homo sapiens brain (cerebral hemispheres). Hypertension inflicts the most damage on the primitive brain. The frontal systems connect to the basal ganglia, then the thalamus and back to the cortex. Many connections converge on the primitive brain where they are damaged by vascular disease. We need methods of determining optimal, individual blood pressures. Although the AGED triad can result from other causes, it should first signal a vascular etiology, the most prevalent, treatable, and preventable one.

SUBMITTER: Hachinski V

PROVIDER: S-EPMC9514311 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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The apathy, gait impairment, and executive dysfunction (AGED) triad vascular variant.

Hachinski Vladimir V Finger Elizabeth E Pieruccini-Faria Frederico F Montero-Odasso Manuel M

Alzheimer's & dementia : the journal of the Alzheimer's Association 20220225 9

Apathy, gait disturbances, and executive dysfunction (AGED) often occur together. Although they can arise independently, the presence of one might portend another. This recognition suggests the possible etiology. We focus on the most common, the vascular. We explain the AGED vascular mechanism through the ambibaric brain concept. The brain contains two complementary blood pressure systems: One high in the primitive brain (brainstem, basal ganglia, and thalamus) and a low-pressure system in the H ...[more]

PMID: 35213766

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Project description:Background: The cognitive and neuropsychiatric deficits present in patients with behavioral variant frontotemporal dementia (bvFTD) are associated with loss of functionality in the activities of daily living (ADLs). The main purpose of this study was to examine and explore the association between the cognitive and neuropsychiatric features that might prompt functional impairment of basic, instrumental, and advanced ADL domains in patients with bvFTD. Methods: A retrospective cross-sectional study was conducted with 27 patients with bvFTD in its early stage (<2 years of evolution) and 32 healthy control subjects. A neuropsychological assessment was carried out wherein measures of cognitive function and neuropsychiatric symptoms were obtained. The informant-report Technology-Activities of Daily Living Questionnaire was used to assess the percentage of functional impairment in the different ADL domains. To identify the best determinants, three separate multiple regression analyses were performed, considering each functional impairment as the dependent variable and executive function, emotion recognition, disinhibition, and apathy as independent variables. Results: For the basic ADLs, a model that explains 28.2% of the variability was found, in which the presence of apathy (β = 0.33, p = 0.02) and disinhibition (β = 0.29, p = 0.04) were significant factors. Concerning instrumental ADLs, the model produced accounted for 63.7% of the functional variability, with the presence of apathy (β = 0.71, p < 0.001), deficits in executive function (β = -0.36, p = 0.002), and lack of emotion recognition (β = 0.28, p = 0.017) as the main contributors. Finally, in terms of advanced ADLs, the model found explained 52.6% of the variance, wherein only the presence of apathy acted as a significant factor (β = 0.59, p < 0.001). Conclusions: The results of this study show the prominent and transverse effect of apathy in the loss of functionality throughout all the ADL domains. Apart from that, this is the first study that shows that the factors associated with loss of functionality differ according to the functional domain in patients with bvFTD in its early stage. Finally, no other study has analyzed the impact of the lack of emotion recognition in the functionality of ADLs. These results could guide the planning of tailored interventions that might enhance everyday activities and the improvement of quality of life.

Project description:ObjectiveTo investigate whether gait dysfunction is a predictor of severe spatial learning and memory impairment in aged mice.MethodsA total of 100 12-month-old male mice that had no obvious abnormal motor ability and whose Morris water maze performances were not significantly different from those of two-month-old male mice were selected for the study. The selected aged mice were then divided into abnormal or normal gait groups according to the results from the quantitative gait assessment. Gaits of aged mice were defined as abnormal when the values of quantitative gait parameters were two standard deviations (SD) lower or higher than those of 2-month-old male mice. Gait parameters included stride length, variability of stride length, base of support, cadence, and average speed. After nine months, mice exhibiting severe spatial learning and memory impairment were separated from mice with mild or no cognitive dysfunction. The rate of severe spatial learning and memory impairment in the abnormal and normal gait groups was tested by a chi-square test and the correlation between gait dysfunction and decline in cognitive function was tested using a diagnostic test.ResultsThe 12-month-old aged mice were divided into a normal gait group (n = 75) and an abnormal gait group (n = 25). Nine months later, three mice in the normal gait group and two mice in the abnormal gait group had died. The remaining mice were subjected to the Morris water maze again, and 17 out of 23 mice in the abnormal gait group had developed severe spatial learning and memory impairment, including six with stride length deficits, 15 with coefficient of variation (CV) in stride length, two with base of support (BOS) deficits, five with cadence dysfunction, and six with average speed deficits. In contrast, only 15 out of 72 mice in the normal gait group developed severe spatial learning and memory impairment. The rate of severe spatial learning and memory impairment was significantly higher in the abnormal gait group as compared to that in the normal gait group (x = 21.986, P < 0.001). All five parameters used to assess gait predicted severe spatial learning and memory impairment in aged mice (P < 0.01). However, the difference of the area under the ROC (receiver operating characteristic) curve for each quantitative gait parameter was not statistically significant.ConclusionGait disorders are a predictor of severe spatial learning and memory impairment in aged mice, and stride length, variability of stride length, base of support, cadence, and average speed are all sensitive parameters for assessing gait.

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The apathy, gait impairment, and executive dysfunction (AGED) triad vascular variant.

Publications

The apathy, gait impairment, and executive dysfunction (AGED) triad vascular variant.

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