Behavioral characteristics of an extremely old rhesus macaque in a zoo: Dementia-like symptoms and implications for quality of life of geriatric animals

This study documents the behavioral changes, gait alterations, and quality of life of an extremely old rhesus macaque with post-mortem evidence of Alzheimer's-like pathology, highlighting potential signs of physical and cognitive decline while emphasizing the need for further controlled testing to confirm dementia in geriatric primates.

The Gist

Imagine a very old, wise monkey named ISK living in a zoo. She wasn't just old; she was a record-breaker, living to be 43 years old (which is like a human living to be over 100). This paper is a story about how she spent her final years, looking at her behavior to see if she was showing signs of "monkey dementia," similar to Alzheimer's in humans.

Here is the story of ISK, broken down simply:

1. The Detective Work: Watching the Monkey

The zookeepers and scientists acted like detectives. They didn't just guess how ISK was feeling; they watched her 24/7 using security cameras, like a continuous home video. They also kept a diary of her daily life.

• The "Sleeping" Pattern: Most of the time, ISK was just sitting still. Imagine a person who used to run marathons but now spends 90% of their day sitting in a chair. That was ISK. She was inactive, eating very little, and moving slowly.
• The Night Owl: While most monkeys sleep soundly at night, ISK was sometimes awake and wandering around when the lights were off. It's like an elderly human who can't sleep and gets up to pace the hallway at 3 AM.

2. The "Lost in the Mall" Moments

The most interesting part of the story involves ISK getting confused. The researchers found a specific video clip that serves as a perfect example of what might have been happening in her brain.

• The Incident: One day, ISK was walking around her outdoor playground. She walked straight into a bush, got tangled in vines, and kept walking forward even though she was stuck. She didn't stop to figure it out; she just kept pushing. Eventually, she walked right into a dry moat (a ditch) and fell in. She couldn't get out on her own and had to be rescued by a keeper.
• The Analogy: Think of it like someone with dementia walking into a wall and not realizing they hit it, or walking into a room and forgetting why they went there, so they just keep walking until they get stuck. ISK seemed to lose her "mental map" of her surroundings.

3. The Walking Waddle

Scientists also looked at how she walked. They compared her steps to younger monkeys.

• The Change: Young monkeys walk with a smooth, rhythmic rhythm, like a well-oiled machine. ISK's walk became clumsy. Her steps were shorter, she moved slower, and her legs didn't coordinate as well. It's the difference between a dancer gliding across the floor and someone shuffling their feet, unsure of where to place them next.

4. The Brain Clues (The "Why")

After ISK passed away naturally, scientists examined her brain. They found physical evidence that explained her behavior:

• The "Gunk" in the Brain: They found clumps of protein (called senile plaques and tau tangles) in her brain. In humans, these clumps are the hallmark of Alzheimer's disease. They act like "gunk" clogging the wires of a computer, making it hard for the brain to process information.
• The Connection: While they couldn't test her brain with a quiz (since she was a monkey), the combination of her confused behavior, her stumbling, and the "gunk" in her brain strongly suggested she was experiencing a form of dementia.

5. Was She Happy? (Quality of Life)

You might think a monkey with dementia would be miserable, but the story has a heartwarming twist.

• The Care Team: The zookeepers and vets were like a dedicated family. They noticed she was struggling and changed her routine. They gave her easier food, kept her in a safer, indoor area so she wouldn't fall, and made sure she wasn't bullied by other monkeys.
• The Result: Even though her brain was failing, her Quality of Life remained surprisingly good until the very end. She wasn't in pain, she was still part of a social group (even if she didn't talk much), and she felt safe. The "gunk" in her brain didn't ruin her happiness because her human caretakers stepped in to fix the problems her brain couldn't solve.

The Big Takeaway

This paper is important because it's one of the first times scientists have connected the dots between behavior (getting lost, walking weirdly) and brain pathology (the physical clumps) in an old monkey.

The Lesson: Just like we need to watch for signs of confusion in our aging grandparents, zookeepers need to watch for these same signs in aging animals. By spotting these "dementia-like" symptoms early, they can adjust the animal's environment to keep them safe and happy, ensuring their final years are comfortable, even if their minds are fading.

In short: ISK was a pioneer. Her life and death taught us that even when an animal's brain starts to fail, with the right care and a little bit of understanding, they can still have a good quality of life.

Technical Summary

1. Problem Statement

The study addresses a critical gap in the understanding of aging in non-human primates, specifically regarding the behavioral manifestation of neurodegenerative diseases. While pathological markers of Alzheimer's disease (such as senile plaques and tau deposition) have been documented in aged primates, there is a scarcity of longitudinal behavioral data linking these pathological findings to observable cognitive decline and Quality of Life (QoL) in a naturalistic setting. Most existing studies focus on either pathology or controlled cognitive testing, lacking the integration of daily behavioral monitoring with post-mortem neuropathology. The authors aim to document the behavioral trajectory of an exceptionally old rhesus macaque to identify potential dementia-like symptoms and assess their impact on welfare.

2. Methodology

The study employed a multi-modal approach combining quantitative behavioral analysis, gait kinematics, clinical QoL scoring, and anecdotal observation of a single subject (ISK), a 43-year-old female rhesus macaque at Kyoto City Zoo.

• Subject: ISK, the longest-living rhesus macaque on record (43 years, 4 months), compared against a control group of 14 other macaques (aged 14–37 years).
• Activity Budgets & Rhythms:
  • Data Collection: 551 hours of 24-hour surveillance video recordings (January–August 2021) for ISK; 108 hours of overnight recordings for 12 younger monkeys (April–August 2023).
  • Analysis: Scan sampling at 5-minute intervals to categorize behaviors (inactive, moving, eating, exploring, social).
  • Statistics: Wilcoxon signed-rank tests compared diurnal vs. nocturnal activity. Z-scores were calculated to determine if ISK's nocturnal activity deviated significantly ($|z| > 2$) from the control group.
• Gait Analysis:
  • Data: Video clips from December 2020 and June 2021 for ISK; 2020–2023 for controls.
  • Metrics: Relative stride length, mean stride duration, relative speed, limb phase, duty factor, and ipsilateral duty factor (asymmetry).
  • Validation: Consistency was verified using two different camera types (GoPro and Trailcam) to ensure measurement reliability.
• Quality of Life (QoL) Assessment:
  • A veterinarian scored ISK monthly from January to September 2021 using a modified 6-domain scale (Pain, Maintenance, Appetite, Locomotion, Object Manipulation, Interaction) on a 1–5 scale.
• Pathological Context: The behavioral data was contextualized against post-mortem findings from a previous study (Iwaide et al., 2023) which confirmed severe amyloid-$\beta$ (A$\beta$) deposition, hyperphosphorylated tau, and small neurofibrillary tangles in ISK's hippocampus.

3. Key Contributions

• First Integrated Case Study: This is one of the few studies to correlate specific behavioral changes in a geriatric primate with confirmed post-mortem Alzheimer's-like neuropathology.
• Behavioral Phenotyping of Dementia: The study adapts the "DISHA" acronym (Disorientation, Interaction, Sleep-wake, House-soiling, Activity) used in canine/feline cognitive dysfunction to identify similar symptoms in primates.
• Objective Gait Metrics for Aging: It provides quantitative gait data (e.g., increased duty factor asymmetry, reduced speed) that distinguishes pathological aging from normal senescence in macaques.
• QoL Monitoring Framework: It demonstrates the utility of combining quantitative video analysis with expert QoL scoring to manage geriatric zoo animals.

4. Key Results

• Activity Budgets: ISK spent the vast majority of her time inactive (89–95%), with a marked decline in active behaviors (exploring, moving) from January to August 2021.
• Sleep-Wake Cycle: While ISK remained primarily diurnal, she exhibited significantly higher nocturnal activity compared to the control group (z-score > 2), indicating a disruption in circadian rhythms.
• Gait Abnormalities:
  • ISK showed significantly slower relative speed ($z = -2.42$) and shorter stride length compared to controls.
  • Asymmetry: She exhibited a significantly higher ipsilateral duty factor ($z = 2.64$) and altered limb phases, suggesting impaired coordination and gait instability.
  • These changes worsened between the first (Dec 2020) and last (June 2021) assessments.
• Cognitive/Disorientation Episodes:
  • Anecdotal records and video analysis revealed specific "dementia-like" behaviors: getting stuck in dry moats, walking into obstacles without stopping, inability to locate food, and reduced reaction to keeper calls.
  • A specific episode on Dec 28, 2020, showed ISK walking into a bush, becoming entangled, and falling into a dry moat, requiring keeper rescue.
• Quality of Life: Despite the pathological and behavioral decline, ISK's QoL scores remained relatively high (mostly 3–4/5) until the final months. She maintained social bonds with two conspecifics and did not exhibit depressive behaviors.
• Pathology-Behavior Link: The unique combination of severe tau pathology and specific behavioral deficits (disorientation, gait changes) in ISK, contrasted with the lack of such pathology in other aged zoo macaques, strongly suggests a pathological cognitive decline.

5. Significance and Implications

• Welfare Management: The study validates that behavioral monitoring (activity budgets, gait, and specific disorientation events) can serve as early warning systems for cognitive decline in zoo primates, allowing for timely husbandry adjustments (e.g., restricting outdoor access, modifying diet).
• Model for Human Aging: The findings support the rhesus macaque as a valuable model for studying the progression of Alzheimer's disease, particularly the disconnect between severe pathology and the preservation of QoL in early-to-mid stages.
• Methodological Advancement: The paper highlights the necessity of combining longitudinal behavioral observation with neuropathology. It suggests that future studies should include systematic cognitive testing alongside behavioral monitoring to definitively diagnose cognitive dysfunction in non-human primates.
• Ethical Considerations: The case underscores that even with significant neurological decline, geriatric animals can maintain a good quality of life through supportive care, challenging the assumption that pathological decline inevitably leads to immediate suffering or the need for euthanasia.

In conclusion, this paper provides a rare, comprehensive documentation of the behavioral trajectory of a super-aged primate with confirmed Alzheimer's-like pathology, offering a framework for monitoring and managing cognitive decline in captive geriatric animals.