天美传媒

Alzheimer's Disease (AD) is the most common cause of dementia, affecting millions of individuals worldwide. It is characterized by the accumulation of amyloid-beta plaques and tau tangles in the brain, leading to progressive neuronal damage and cognitive decline. The clinical manifestations of AD typically include memory loss, language difficulties, impaired judgment and changes in behavior and personality [1].

A 72-year-old woman, presented to the neurology clinic with complaints of progressive memory loss and difficulty performing daily tasks. Her family reported that she had become increasingly forgetful over the past two years, often repeating herself and misplacing household items. She also exhibited confusion regarding time and location, frequently getting lost even in familiar surroundings [2].

Upon further evaluation, Mrs. A underwent a comprehensive neurological examination, including cognitive assessment tools such as the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) (Table 1 and Figure 1). Her MMSE score was 15/30, indicating moderate cognitive impairment, while her MoCA score was 18.10/30, suggestive of severe cognitive impairment [3].

Table 1: MMSE examination of patient.

 

Figure 1: MoCA examination of patient.

Further investigations, including brain imaging with Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET), revealed bilateral temporal and parietal lobe atrophy, as well as increased amyloid-beta deposition consistent with a diagnosis of Alzheimer's disease [4].

Diagnostic challenges

Diagnosing Alzheimer's disease can be challenging due to its insidious onset and overlapping symptoms with other forms of dementia. Differential diagnoses may include vascular dementia, Lewy body dementia, frontotemporal dementia or reversible causes such as vitamin deficiencies or thyroid dysfunction [5].

In Mrs. A's case, the presence of progressive memory loss, executive dysfunction and characteristic neuroimaging findings supported the diagnosis of AD. However, ruling out other potential etiologies required a thorough clinical evaluation and ancillary testing [6].

Treatment strategies

Currently, there is no cure for Alzheimer's disease and available treatments aim to alleviate symptoms and slow disease progression. Pharmacological interventions such as acetylcholinesterase inhibitors (e.g., donepezil, rivastigmine) and N-Methyl-D-Aspartate (NMDA) receptor antagonists (e.g., memantine) may provide modest benefits in cognition and function [7].

In addition to pharmacotherapy, non-pharmacological interventions play a crucial role in managing AD-related symptoms. These may include cognitive stimulation programs, physical exercise, dietary modifications and behavioral therapies tailored to the individual's needs.

Caregiver

Caring for a loved one with Alzheimer's disease can be emotionally and physically demanding, often leading to caregiver burden and burnout. Family members may experience stress, depression, social isolation and financial strain as they navigate the challenges of caregiving.

In Mrs. A's case, her husband assumed primary caregiving responsibilities, providing assistance with activities of daily living, medication management and emotional support. However, he struggled with feelings of guilt, frustration and grief as he witnessed his wife's cognitive decline and functional impairment [8].

Background and aims

The current state of advance directives in the United States allows only limited options to people facing a diagnosis of Alzheimer’s disease. Existing options focus on choices involving the final stages of Alzheimer’s, e.g., refusing feeding tubes when one can no longer swallow. Our question was whether these choices responded to the concerns of many Americans. Our hypothesis was that a substantial number might wish their lives to end at earlier stages.

Experimental practice

Several clinical data already have shown that inhibition of Angiotensin Converting Enzyme (ACE) retards the process of neurodegeneration leading to dementia and the incidence of AD. Data from clinical practice confirm that the neuroprotective activity is linked to centrally acting ACE inhibitors The effect of central ACE inhibition leads to reduced activation of Additional Tier-1 (AT1) receptor; in fact, the neuroprotective effects of centrally acting AT1 receptor antagonists appear to be even stronger. A recent study determined the treatment effect of centrally acting ACE inhibitors as add-on therapy to an acetylcholinesterase inhibitor in AD patients. Outcome data of this study show that a centrally acting ACE inhibitor could improve AD dementia symptoms for about 9 months after diagnosis of AD, compared to the treatment with a non-centrally acting ACE inhibitor, which led to a deterioration of cognitive function. This is a remarkable success considering that the last drug approval for AD, i.e., memantine, was about 15 years ago. Although, ACE inhibitors do not cure AD, the significant improvement of symptoms of dementia with these within 9 months is a much better outcome compared to the one with Abeta-targeting approaches in phase III clinical trials, which did not find any measurable effect on AD symptoms. A recent overview of all clinical trials of amyloidbeta-targeting therapies for Alzheimer disease supports this conclusion. Even if there are still Abeta-targeting drug candidates with apparently promising results in early stages of clinical development, the failure of all amyloid-beta-targeting compounds in large clinical trials during the past 20 years does not leave much room for expectations to achieve substantial clinical benefit with the amyloidbeta-targeting approach in the future [9].

Alzheimer's disease poses significant challenges for patients, caregivers and healthcare providers alike. Early recognition of symptoms, accurate diagnosis and multidisciplinary management are essential for optimizing patient outcomes and enhancing quality of life.

As research continues to advance, new insights into the pathophysiology of AD may pave the way for innovative therapeutic strategies and personalized approaches to care. In the meantime, raising awareness, providing support services and advocating for policy changes are crucial steps in addressing the growing impact of dementia on individuals and society as a whole.

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

We gratefully acknowledge the Fundamental Research Funds for the Central Universities for financial support of this work. We gratefully acknowledge, Ministry of Education. We would also like to acknowledge University of Guelph and University of waterloo for their module for this work.

1. Xie JK, Zhu XX, Wang KX, Wang SC, Xie Q (2021) . Appl Radiat Isot 174: 109740.

   [] [] []

2. Shahim B, Xu H, Haugaa K, Zetterberg H, Jurga J, et al. (2024) . Eur Heart J Cardiovasc Pharmacother 10: 128-136.

   [] [] []

3. Ehrhardt S, Porsteinsson AP, Munro CA, Rosenberg PB, Pollock BG, et al. (2019) . Alzheimers Dement 15: 1427-1436.

   [] [] []

4. Espinosa-Fernández V, Mañas-Ojeda A, Pacheco-Herrero M, Castro-Salazar E, Ros-Bernal F, et al. (2019) . Behav Brain Res 374: 112106.

   [] [] []

5. Venkatesh R, Shankar G, Narayanan AC, Modi G, Sabiah S, et al. . J Org Chem 87: 6730-6741.

   [] [] []

6. McDonald K, Ledwidge M, Cahill J, Quigley P, Maurer B, et al. (2002) . J Card Fail 8: 142-148.

   [] []

7. El Saghir NS, Keating NL, Carlson RW, Khoury KE, Fallowfield L (2014) Tumor boards: Optimizing the structure and improving efficiency of multidisciplinary management of patients with cancer worldwide. Ame Soc Clin Oncol Educ Book 34: e461-e466.

   []

8. Ang KK (2008) . Oncol 13: 899-910.

   [] []

9. Rodr谋虂guez JF, Renaud JE, Wujek BA, Tappeta RV (2000) . J Comput Appl Math 124: 139-154.

   [] []