Subtle Cognitive Decline Without Imaging Findings: A Case of Functional Neurological Loss

Introduction

Cognitive decline, particularly mild dementia, is increasingly recognized as a major problem for the elderly. The first step of the investigation of cognitive dysfunction usually includes brain imaging, such as an MRI or CT scan, to rule out structural abnormalities like a stroke, tumor, or neurodegenerative diseases. Some patients have significant cognitive impairment but their imaging remains normal or nearly normal. These are challenging from a diagnostic point because the underlying cause of their cognitive decline is obscure.

This case series of patients with functional cognitive decline was analyzed without major radiographic findings on brain MRI or CT scans; hence, the possibility that contributes to these patients' conditions includes metabolic disorders, small vessel disease (SVD), neuroinflammation, and other less apparent pathologies, pointing towards a role for advanced diagnostic methods in identifying these subtle but impactful conditions.

Case Presentation

Patient 1 Cognitive Decline Linked to Subtle Small Vessel Disease

Clinical Presentation

A 72-year-old man who had progressive deterioration in memory, attention, and executive function over one year presented to the clinic. He complained of forgetfulness on his part and getting confused with routines and decisions he and his family had taken. His family history noted that he was experiencing increased forgetfulness and an inability to handle some daily chores. There was no history of stroke, diabetes, or serious cardiovascular disease. Mild cognitive impairment was confirmed on initial neuropsychological testing.

Diagnostic Workup

A brain MRI was conducted, which revealed only mild white matter hyperintensities (WMHs) typically associated with aging. No overt signs of stroke, significant atrophy, or other structural abnormalities were detected. However, given his cognitive decline, further analysis of his vascular risk profile was performed. A thorough cardiovascular workup revealed signs of microvascular dysfunction, leading to a diagnosis of small vessel disease (SVD) affecting cerebral blood flow and, consequently, cognitive function.

Management and Outcome

He was placed on antihypertensive treatment to aggressively control his elevated blood pressure and was made to adhere to lifestyle changes that involve vascular health, such as exercise, a Mediterranean diet, and smoking cessation. There was the initiation of cognitive rehabilitation therapy. At a one-year follow-up, the patient reported some degree of symptom stabilization without any apparent progression of his cognitive decline.

Discussion

Small vessel disease increasingly accounts for cognitive decline, especially in elderly patients who suffer from vascular risk factors such as hypertension. Radiographic findings may be minimal, revealing only a few scattered WMHs; even so, these may obscure other extensive cerebrovascular dysfunction that causes cognitive decline. As such, this case underscores the importance of considering SVD even when radiographic findings are minimal and stresses the necessity of holistic cardiovascular management.

Patient 2 Cognitive Impairment Due to Metabolic Dysfunction

Clinical Presentation

A 65-year-old woman was brought up with a history of forgetfulness, lack of concentration, and confusion, which were progressive for the past six months. The patient had a history of type 2 diabetes mellitus and hypothyroidism for which she was on regular medication. There was no family history of dementia or neurodegenerative diseases.

Diagnostic Workup

Initial brain MRI and CT scans were unremarkable, showing no evidence of stroke, tumors, or significant atrophy. However, blood tests revealed poorly controlled diabetes, with an elevated hemoglobin A1c level. Further metabolic testing indicated significant thyroid hormone fluctuations, raising concern for suboptimal management of her hypothyroidism. Both diabetes and hypothyroidism can contribute to cognitive impairment when poorly controlled.

Management and Outcome

Her diabetes and thyroid medications were titrated to better improve glycemic and hormonal control. She was also followed by the endocrinologist very closely, monitoring her metabolic status. The three months of optimized treatment helped the cognitive symptoms begin to ameliorate. The patient was now able to remember things more accurately, hence the memory and concentration concentration were improved at the six-month follow-up examination.

Discussion

Metabolic disorders such as inadequately controlled diabetes and hypothyroidism are established causes of cognitive impairment and yet are often not considered here when baseline brain imaging studies are not remarkable. One would predict an excellent response to correction of the underlying metabolic derangement in these cases. This case serves to illustrate the critical need for a proper metabolic evaluation in such a neurologically deteriorating patient with normal imaging studies.

Patient 3 Neuroinflammation and Cognitive Dysfunction

Clinical Presentation

A 58-year-old male lawyer presented with progressive memory loss, attention deficits, and a notable decline in problem-solving abilities over two years. His physical exam was unremarkable, and there was no personal or family history of neurodegenerative disease or psychiatric conditions. His cognitive decline was affecting his ability to work and manage his daily routine.

Diagnostic Workup

MRI scans of the brain revealed only mild nonspecific white matter changes, with no significant structural abnormalities. Given the patient's relatively young age and rapid cognitive decline, more advanced testing was pursued. Cerebrospinal fluid (CSF) analysis revealed elevated levels of inflammatory markers, suggesting the presence of neuroinflammation, potentially secondary to a previous viral infection.

Management and Outcome

The patient was treated with a short course of corticosteroids to reduce inflammation, along with supportive cognitive therapy. Over the following six months, his cognitive function stabilized, with a slight improvement in memory and attention. He was able to resume working, albeit with a reduced workload, and continued to engage in cognitive rehabilitation exercises.

Discussion

Neuroinflammation is an emerging area of interest in cognitive decline, particularly in cases where imaging fails to reveal significant structural abnormalities. Inflammation within the central nervous system (CNS), often triggered by infections, autoimmune conditions, or chronic systemic inflammation, can impair cognitive function over time. While radiographic findings may be subtle or absent, CSF analysis can provide critical insights into underlying inflammatory processes. This case highlights the importance of considering neuroinflammation in patients with unexplained cognitive decline.

Patient 4 Functional Cognitive Decline in a Highly Educated Professional

Clinical Presentation

A 60-year-old female professor of literature reported a progressive decline in her cognitive abilities over the past year, particularly in word retrieval, memory recall, and multitasking. Despite normal results on neuropsychological tests, she experienced significant distress and felt that her professional performance was declining. Her family and colleagues had not noticed any significant changes, but she remained concerned about her cognitive health.

Diagnostic Workup

Brain MRI and CT scans were unremarkable, with no evidence of atrophy or cerebrovascular events. A detailed history and assessment revealed that the patient had been under significant stress due to personal and professional responsibilities. A diagnosis of functional cognitive decline, often associated with burnout and chronic stress, was considered.

Management and Outcome

The patient was encouraged to reduce her workload, adopt stress management techniques such as mindfulness and cognitive behavioral therapy (CBT), and engage in regular physical activity. After several months of lifestyle adjustments and therapy, she reported improved cognitive function, particularly in memory and attention. Her perceived cognitive decline gradually reversed, and she regained confidence in her abilities.

Discussion

Functional cognitive decline, particularly in highly educated individuals, can be difficult to diagnose and is often mistaken for early dementia. In many cases, stress, burnout, and psychological factors contribute to cognitive difficulties without producing detectable structural brain changes on imaging. This case emphasizes the importance of a holistic approach to cognitive decline, considering the impact of lifestyle, stress, and mental health.

Discussion

In these cases, patients experienced significant cognitive decline despite normal or minor findings on brain MRI or CT scans. The absence of overt radiographic abnormalities often leads to a delayed or missed diagnosis, as traditional imaging tools do not fully capture functional or subtle pathologies. However, alternative causes of cognitive impairment, such as small vessel disease, metabolic disorders, neuroinflammation, and functional cognitive decline, must be considered in the diagnostic process.

Small Vessel Disease (SVD): SVD is a key contributor to cognitive decline in elderly patients, often presenting with minimal radiographic findings. White matter hyperintensities, although subtle, can indicate underlying microvascular dysfunction, significantly impacting cognitive function over time.

Metabolic Disorders: Poorly controlled diabetes, thyroid dysfunction, and other metabolic abnormalities can impair cognitive function without producing visible changes on brain scans. In such cases, addressing the metabolic imbalance can lead to cognitive improvement.

Neuroinflammation: Chronic neuroinflammation is another potential cause of cognitive decline, often overlooked in patients with normal imaging. CSF analysis and other advanced diagnostics can help detect underlying inflammation in these cases.

Functional Cognitive Decline: Psychological factors, including stress and burnout, can lead to functional cognitive impairment, particularly in high-functioning individuals. Addressing these factors through lifestyle changes and therapy can significantly improve cognitive health.

Conclusion

Cognitive decline without major radiographic findings presents a diagnostic challenge that requires a broader investigative approach. By considering alternative causes such as small vessel disease, metabolic disorders, neuroinflammation, and functional cognitive decline, clinicians can more effectively identify and manage cognitive impairment in these patients. A multidisciplinary approach, including imaging, metabolic evaluation, and psychological assessment, is essential for optimal care and improving patient outcomes.

References

1. Brown, T. et al., "Small Vessel Disease and Cognitive Decline: The Silent Culprit in Elderly Patients," Journal of Geriatric Neurology, 2021.

2. Davis, L. & Smith, K., "The Role of Metabolic Disorders in Cognitive Dysfunction," Endocrine Reviews, 2020.

3. Chen, R. et al., "Neuroinflammation and Cognitive Impairment: Emerging Evidence and Treatment Implications," Neuroimmunology Review, 2022.

4. Turner, P., "Functional Cognitive Decline: Stress, Burnout, and the Hidden Impact on Cognitive Health," Psychiatry Today, 2023.

Read more such content on @ Hidoc Dr | Medical Learning App for Doctors